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Volume 168, Issue 12

Bacterial survivors: evaluating the mechanisms of antibiotic persistence Open Access

This article is part of the Environmental Sensing and Cell-Cell Communication collection

Abstract

Bacteria withstand antibiotic onslaughts by employing a variety of strategies, one of which is persistence. Persistence occurs in a bacterial population where a subpopulation of cells (persisters) survives antibiotic treatment and can regrow in a drug-free environment. Persisters may cause the recalcitrance of infectious diseases and can be a stepping stone to antibiotic resistance, so understanding persistence mechanisms is critical for therapeutic applications. However, current understanding of persistence is pervaded by paradoxes that stymie research progress, and many aspects of this cellular state remain elusive. In this review, we summarize the putative persister mechanisms, including toxin–antitoxin modules, quorum sensing, indole signalling and epigenetics, as well as the reasons behind the inconsistent body of evidence. We highlight present limitations in the field and underscore a clinical context that is frequently neglected, in the hope of supporting future researchers in examining clinically important persister mechanisms.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antibiotics , indole signalling , persister , quorum sensing , stress response and toxin/antitoxins
Funding
This study was supported by the:
  • Isaac Newton Trust (Award 21.22(a)iii)
    • Principle Award Recipient: AshrafZarkan
  • Rosetrees Trust (Award JS16/TTI2021\1)
    • Principle Award Recipient: AshrafZarkan
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-12-06
2024-04-23
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References

  1. Antimicrobial Resistance Collaborators Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 2022; 399:629–655 [View Article] [PubMed]
     [Google Scholar]
  2. Blanchard SC. A much-needed boost for the dwindling antibiotic pipeline. Mol Cell 2018; 70:3–5 [View Article] [PubMed]
     [Google Scholar]
  3. Resistance R on A Antimicrobial resistance: tackling a crisis for the health and wealth of nations Review on Antimicrobial Resistance; 2014
     [Google Scholar]
  4. Wilmaerts D, Windels EM, Verstraeten N, Michiels J. General mechanisms leading to persister formation and awakening. Trends Genet 2019; 35:401–411 [View Article] [PubMed]
     [Google Scholar]
  5. Bigger JosephW. Treatment of staphylococcal infections with penicillin by intermittent sterilisation. The Lancet 1944; 244:497–500 [View Article]
     [Google Scholar]
  6. Harms A, Maisonneuve E, Gerdes K. Mechanisms of bacterial persistence during stress and antibiotic exposure. Science 2016; 354:aaf4268 [View Article] [PubMed]
     [Google Scholar]
  7. Balaban NQ, Helaine S, Lewis K, Ackermann M, Aldridge B et al. Definitions and guidelines for research on antibiotic persistence. Nat Rev Microbiol 2019; 17:441–448 [View Article] [PubMed]
     [Google Scholar]
  8. Levin-Reisman I, Ronin I, Gefen O, Braniss I, Shoresh N et al. Antibiotic tolerance facilitates the evolution of resistance. Science 2017; 355:826–830 [View Article] [PubMed]
     [Google Scholar]
  9. Fraikin N, Goormaghtigh F, Van Melderen L. Toxin-Antitoxin Systems and Persistence. In Lewis K. eds Persister Cells and Infectious Disease Cham: Springer International Publishing; 2019 pp 181–202
     [Google Scholar]
  10. Fernandez-García L, Blasco L, Trastoy R, García R, Wood TK et al. Quorum Sensing Systems and Persistence 11
     [Google Scholar]
  11. Zarkan A, Liu J, Matuszewska M, Gaimster H, Summers DK. Local and universal action: the paradoxes of indole signalling in bacteria. Trends Microbiol 2020; 28:566–577 [View Article] [PubMed]
     [Google Scholar]
  12. Riber L, Hansen LH. Epigenetic memories: the hidden drivers of bacterial persistence?. Trends Microbiol 2021; 29:190–194 [View Article] [PubMed]
     [Google Scholar]
  13. Shultis MW, Mulholland CV, Berney M. Are all antibiotic persisters created equal?. Front Cell Infect Microbiol 2022; 12:933458 [View Article] [PubMed]
     [Google Scholar]
  14. Singh G, Yadav M, Ghosh C, Rathore JS. Bacterial toxin-antitoxin modules: classification, functions, and association with persistence. Curr Res Microb Sci 2021; 2:100047 [View Article] [PubMed]
     [Google Scholar]
  15. Ramage HR, Connolly LE, Cox JS. Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLOS Genet 2009; 5:e1000767 [View Article] [PubMed]
     [Google Scholar]
  16. Yu X, Gao X, Zhu K, Yin H, Mao X et al. Characterization of a toxin-antitoxin system in Mycobacterium tuberculosis suggests neutralization by phosphorylation as the antitoxicity mechanism. Commun Biol 2020; 3:216 [View Article] [PubMed]
     [Google Scholar]
  17. Berghoff BA, Wagner EGH. Persister Formation Driven by TisB-Dependent Membrane Depolarization. In Lewis K. eds Persister Cells and Infectious Disease Cham: Springer International Publishing; 2019 pp 77–97
     [Google Scholar]
  18. Podlesek Z, Žgur Bertok D. The DNA damage inducible SOS response is a key player in the generation of bacterial persister cells and population wide tolerance. Front Microbiol 2020; 11:1785 [View Article] [PubMed]
     [Google Scholar]
  19. LeRoux M, Laub MT. Toxin-antitoxin systems as phage defense elements. Annu Rev Microbiol 2022; 76:21–43 [View Article] [PubMed]
     [Google Scholar]
  20. Lou C, Li Z, Ouyang Q. A molecular model for persister in E. coli. J Theor Biol 2008; 255:205–209 [View Article] [PubMed]
     [Google Scholar]
  21. Moyed HS, Bertrand KP. hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis. J Bacteriol 1983; 155:768–775 [View Article] [PubMed]
     [Google Scholar]
  22. Schumacher MA, Balani P, Min J, Chinnam NB, Hansen S et al. HipBA-promoter structures reveal the basis of heritable multidrug tolerance. Nature 2015; 524:59–64 [View Article] [PubMed]
     [Google Scholar]
  23. Narimisa N, Kalani BS, Amraei F, Mohammadzadeh R, Mirkalantari S et al. Type II toxin/antitoxin system genes expression in persister cells of Klebsiella pneumoniae. Reviews in Medical Microbiology 2020; 31:215–220 [View Article]
     [Google Scholar]
  24. Narimisa N, Amraei F, Kalani BS, Azarnezhad A, Jazi FM. Biofilm establishment, biofilm persister cell formation, and relative gene expression analysis of type II toxin-antitoxin system in Klebsiella pneumoniae. Gene Reports 2020; 21:100846 [View Article]
     [Google Scholar]
  25. Falla TJ, Chopra I. Joint tolerance to β-lactam and fluoroquinolone antibiotics in Escherichia coli results from overexpression of hipA. Antimicrob Agents Chemother 1998; 42:3282–3284 [View Article]
     [Google Scholar]
  26. Korch SB, Hill TM. Ectopic overexpression of wild-type and mutant hipA genes in Escherichia coli: effects on macromolecular synthesis and persister formation. J Bacteriol 2006; 188:3826–3836 [View Article] [PubMed]
     [Google Scholar]
  27. Vázquez-Laslop N, Lee H, Neyfakh AA. Increased persistence in Escherichia coli caused by controlled expression of toxins or other unrelated proteins. J Bacteriol 2006; 188:3494–3497 [View Article] [PubMed]
     [Google Scholar]
  28. Keren I, Shah D, Spoering A, Kaldalu N, Lewis K. Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli. J Bacteriol 2004; 186:8172–8180 [View Article] [PubMed]
     [Google Scholar]
  29. Hansen S, Lewis K, Vulić M. Role of global regulators and nucleotide metabolism in antibiotic tolerance in Escherichia coli. Antimicrob Agents Chemother 2008; 52:2718–2726 [View Article] [PubMed]
     [Google Scholar]
  30. Luidalepp H, Jõers A, Kaldalu N, Tenson T. Age of inoculum strongly influences persister frequency and can mask effects of mutations implicated in altered persistence. J Bacteriol 2011; 193:3598–3605 [View Article] [PubMed]
     [Google Scholar]
  31. Korch SB, Henderson TA, Hill TM. Characterization of the hipA7 allele of Escherichia coli and evidence that high persistence is governed by (p)ppGpp synthesis. Mol Microbiol 2003; 50:1199–1213 [View Article] [PubMed]
     [Google Scholar]
  32. Germain E, Roghanian M, Gerdes K, Maisonneuve E. Stochastic induction of persister cells by HipA through (p)ppGpp-mediated activation of mRNA endonucleases. Proc Natl Acad Sci U S A 2015; 112:5171–5176 [View Article] [PubMed]
     [Google Scholar]
  33. Huang CY, Gonzalez-Lopez C, Henry C, Mijakovic I, Ryan KR. hipBA toxin-antitoxin systems mediate persistence in Caulobacter crescentus. Sci Rep 2020; 10:2865 [View Article] [PubMed]
     [Google Scholar]
  34. Hosseini M, Nowroozi J, Amirmozafari N. The effect of type II toxin-antitoxin systems on methicillinresistant Staphylococcus aureus persister cell formation and antibiotic tolerance. Acta Biol Szeged 2021; 65:113–117 [View Article]
     [Google Scholar]
  35. Karimaei S, Kazem Aghamir SM, Foroushani AR, Pourmand MR. Antibiotic tolerance in biofilm persister cells of Staphylococcus aureus and expression of toxin-antitoxin system genes. Microb Pathog 2021; 159:105126 [View Article] [PubMed]
     [Google Scholar]
  36. Conlon BP, Rowe SE, Gandt AB, Nuxoll AS, Donegan NP et al. Persister formation in Staphylococcus aureus is associated with ATP depletion. Nat Microbiol 2016; 1:16051 [View Article] [PubMed]
     [Google Scholar]
  37. Kamruzzaman M, Iredell J. A ParDE-family toxin antitoxin system in major resistance plasmids of Enterobacteriaceae confers antibiotic and heat tolerance. Sci Rep 2019; 9:9872 [View Article] [PubMed]
     [Google Scholar]
  38. Kim Y, Wood TK. Toxins Hha and CspD and small RNA regulator Hfq are involved in persister cell formation through MqsR in Escherichia coli. Biochem Biophys Res Commun 2010; 391:209–213 [View Article] [PubMed]
     [Google Scholar]
  39. Shah D, Zhang Z, Khodursky AB, Kaldalu N, Kurg K et al. Persisters: a distinct physiological state of E. coli. BMC Microbiol 2006; 6:53 [View Article] [PubMed]
     [Google Scholar]
  40. Fraikin N, Rousseau CJ, Goeders N, Van Melderen L. Reassessing the role of the type II MqsRA toxin-antitoxin system in stress response and biofilm formation: mqsA is transcriptionally uncoupled from mqsR. mBio 2019; 10:e02678-19 [View Article] [PubMed]
     [Google Scholar]
  41. Qi X, Brothers KM, Ma D, Mandell JB, Donegan NP et al. The Staphylococcus aureus toxin-antitoxin system YefM-YoeB is associated with antibiotic tolerance and extracellular dependent biofilm formation. J Bone Jt Infect 2021; 6:241–253 [View Article] [PubMed]
     [Google Scholar]
  42. Ma D, Gu H, Shi Y, Huang H, Sun D et al. Edwardsiella piscicida YefM-YoeB: a type II toxin-antitoxin system that is related to antibiotic resistance, biofilm formation, serum survival, and host infection. Front Microbiol 2021; 12:646299 [View Article] [PubMed]
     [Google Scholar]
  43. Ramisetty BCM, Ghosh D, Roy Chowdhury M, Santhosh RS. What is the link between stringent response, Endoribonuclease encoding type II toxin-antitoxin systems and persistence?. Front Microbiol 2016; 7:1882 [View Article]
     [Google Scholar]
  44. Chowdhury N, Kwan BW, Wood TK. Persistence increases in the absence of the alarmone guanosine tetraphosphate by reducing cell growth. Sci Rep 2016; 6:20519 [View Article] [PubMed]
     [Google Scholar]
  45. Harrison JJ, Wade WD, Akierman S, Vacchi-Suzzi C, Stremick CA et al. The chromosomal toxin gene yafQ is a determinant of multidrug tolerance for Escherichia coli growing in a biofilm. Antimicrob Agents Chemother 2009; 53:2253–2258 [View Article] [PubMed]
     [Google Scholar]
  46. Masuda Y, Sakamoto E, Honjoh K-I, Miyamoto T. Role of toxin-antitoxin-regulated persister population and indole in bacterial heat tolerance. Appl Environ Microbiol 2020; 86:e00935-20 [View Article] [PubMed]
     [Google Scholar]
  47. Bernier SP, Lebeaux D, DeFrancesco AS, Valomon A, Soubigou G et al. Starvation, together with the SOS response, mediates high biofilm-specific tolerance to the fluoroquinolone ofloxacin. PLoS Genet 2013; 9:e1003144 [View Article]
     [Google Scholar]
  48. Slattery A, Victorsen AH, Brown A, Hillman K, Phillips GJ. Isolation of highly persistent mutants of Salmonella enterica serovar typhimurium reveals a new toxin-antitoxin module. J Bacteriol 2013; 195:647–657 [View Article] [PubMed]
     [Google Scholar]
  49. Helaine S, Cheverton AM, Watson KG, Faure LM, Matthews SA et al. Internalization of Salmonella by macrophages induces formation of nonreplicating persisters. Science 2014; 343:204–208 [View Article] [PubMed]
     [Google Scholar]
  50. Claudi B, Spröte P, Chirkova A, Personnic N, Zankl J et al. Phenotypic variation of Salmonella in host tissues delays eradication by antimicrobial chemotherapy. Cell 2014; 158:722–733 [View Article] [PubMed]
     [Google Scholar]
  51. Tripathi A, Dewan PC, Siddique SA, Varadarajan R. MazF-induced growth inhibition and persister generation in Escherichia coli. J Biol Chem 2014; 289:4191–4205 [View Article] [PubMed]
     [Google Scholar]
  52. Ma D, Mandell JB, Donegan NP, Cheung AL, Ma W et al. The toxin-antitoxin MazEF drives Staphylococcus aureus biofilm formation, Antibiotic Tolerance, and Chronic Infection. mBio 2019; 10: [View Article]
     [Google Scholar]
  53. Bleriot I, Blasco L, Delgado-Valverde M, Gual-de-Torrella A, Ambroa A et al. Mechanisms of tolerance and resistance to chlorhexidine in clinical strains of Klebsiella pneumoniae producers of carbapenemase: role of new type II toxin-antitoxin system, PemIK. Toxins 2020; 12:566 [View Article] [PubMed]
     [Google Scholar]
  54. Sharma A, Chattopadhyay G, Chopra P, Bhasin M, Thakur C et al. VapC21 toxin contributes to drug-tolerance and interacts with non-cognate VapB32 Antitoxin in Mycobacterium tuberculosis. Front Microbiol 2020; 11: [View Article] [PubMed]
     [Google Scholar]
  55. Xia K, Han C, Xu J, Liang X. Toxin-antitoxin HicAB regulates the formation of persister cells responsible for the acid stress resistance in Acetobacter pasteurianus. Appl Microbiol Biotechnol 2021; 105:725–739 [View Article] [PubMed]
     [Google Scholar]
  56. Cheverton AM, Gollan B, Przydacz M, Wong CT, Mylona A et al. A Salmonella toxin promotes persister formation through acetylation of tRNA. Mol Cell 2016; 63:86–96 [View Article]
     [Google Scholar]
  57. Zhou J, Li S, Li H, Jin Y, Bai F et al. Identification of a toxin-antitoxin system that contributes to persister formation by reducing NAD in Pseudomonas aeruginosa. Microorganisms 2021; 9:753 [View Article]
     [Google Scholar]
  58. Dufour D, Mankovskaia A, Chan Y, Motavaze K, Gong S-G, Lévesque CM. 2018; A tripartite toxin-antitoxin module induced by quorum sensing is associated with the persistence phenotype in Streptococcus mutans. Mol Oral Microbiol 33:420–429
     [Google Scholar]
  59. Norton JP, Mulvey MA, Tran Van Nhieu G. Toxin-antitoxin systems are important for niche-specific colonization and stress resistance of uropathogenic Escherichia coli. PLoS Pathog 2012; 8:e1002954 [View Article]
     [Google Scholar]
  60. Fino C, Vestergaard M, Ingmer H, Pierrel F, Gerdes K et al. PasT of Escherichia coli sustains antibiotic tolerance and aerobic respiration as a bacterial homolog of mitochondrial Coq10. Microbiologyopen 2020; 9:e1064 [View Article]
     [Google Scholar]
  61. Van Acker H, Crabbé A, Jurėnas D, Ostyn L, Sass A et al. The role of small proteins in Burkholderia cenocepacia J2315 biofilm formation, persistence and intracellular growth. Biofilm 2019; 1:100001 [View Article] [PubMed]
     [Google Scholar]
  62. Ross BN, Thiriot JD, Wilson SM, Torres AG. Predicting toxins found in toxin-antitoxin systems with a role in host-induced Burkholderia pseudomallei persistence. Sci Rep 2020; 10:16923 [View Article] [PubMed]
     [Google Scholar]
  63. Verstraeten N, Knapen WJ, Kint CI, Liebens V, Van den Bergh B et al. Obg and membrane depolarization are part of a microbial bet-hedging strategy that leads to antibiotic tolerance. Mol Cell 2015; 59:9–21 [View Article]
     [Google Scholar]
  64. Edelmann D, Oberpaul M, Schäberle TF, Berghoff BA. Post-transcriptional deregulation of the tisB/istR-1 toxin-antitoxin system promotes SOS-independent persister formation in Escherichia coli. Environ Microbiol Rep 2021; 13:159–168 [View Article]
     [Google Scholar]
  65. Berghoff BA, Hoekzema M, Aulbach L, Wagner EGH. Two regulatory RNA elements affect TisB-dependent depolarization and persister formation. Molecular Microbiology 2017; 103:1020–1033 [View Article] [PubMed]
     [Google Scholar]
  66. Edelmann D, Leinberger FH, Schmid NE, Oberpaul M, Schäberle TF et al. Elevated expression of toxin TisB protects persister cells against ciprofloxacin but enhances susceptibility to Mitomycin C. Microorganisms 2021; 9:943 [View Article] [PubMed]
     [Google Scholar]
  67. Edelmann D, Berghoff BA. A shift in perspective: a role for the type I toxin TisB as persistence-stabilizing factor. Front Microbiol 2022; 13:871699 [View Article]
     [Google Scholar]
  68. Coray DS, Wheeler NE, Heinemann JA, Gardner PP. Why so narrow: distribution of anti-sense regulated, type I toxin-antitoxin systems compared with type II and type III systems. RNA Biol 2017; 14:275–280 [View Article]
     [Google Scholar]
  69. Tsilibaris V, Maenhaut-Michel G, Mine N, Van Melderen L. What is the benefit to Escherichia coli of having multiple toxin-antitoxin systems in its genome?. J Bacteriol 2007; 189:6101–6108 [View Article] [PubMed]
     [Google Scholar]
  70. LeRoux M, Culviner PH, Liu YJ, Littlehale ML, Laub MT. Stress can induce transcription of toxin-antitoxin systems without activating toxin. Mol Cell 2020; 79:280–292 [View Article]
     [Google Scholar]
  71. Pontes MH, Groisman EA. Slow growth dictates non-heritable antibiotic resistance in Salmonella enterica. Sci Signal 2019; 12:eaax3938 [View Article]
     [Google Scholar]
  72. Gray MJ. Inorganic polyphosphate accumulation in Escherichia coli is regulated by DksA but not by (p)ppGpp. J Bacteriol 2019; 201:e00664-18 [View Article]
     [Google Scholar]
  73. Boutte CC, Henry JT, Crosson S. ppGpp and polyphosphate modulate cell cycle progression in Caulobacter crescentus. J Bacteriol 2012; 194:28–35 [View Article] [PubMed]
     [Google Scholar]
  74. Racki LR, Tocheva EI, Dieterle MG, Sullivan MC, Jensen GJ et al. Polyphosphate granule biogenesis is temporally and functionally tied to cell cycle exit during starvation in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 2017; 114:E2440–E2449 [View Article]
     [Google Scholar]
  75. Bhaskar A, De Piano C, Gelman E, McKinney JD, Dhar N. Elucidating the role of (p)ppGpp in mycobacterial persistence against antibiotics. IUBMB Life 2018; 70:836–844 [View Article] [PubMed]
     [Google Scholar]
  76. Harms A, Fino C, Sørensen MA, Semsey S, Gerdes K et al. Prophages and growth dynamics confound experimental results with antibiotic-tolerant persister cells. mBio 2017; 8: [View Article] [PubMed]
     [Google Scholar]
  77. Osbourne DO, Soo VW, Konieczny I, Wood TK. Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro Lon activity. Bioengineered 2014; 5:264–268 [View Article] [PubMed]
     [Google Scholar]
  78. Theodore A, Lewis K, Vulić M. Tolerance of Escherichia coli to fluoroquinolone antibiotics depends on specific components of the SOS response pathway. Genetics 2013; 195:1265–1276 [View Article] [PubMed]
     [Google Scholar]
  79. Song S, Wood TK. Toxin/antitoxin system paradigms: toxins bound to antitoxins are not likely activated by preferential antitoxin degradation. Adv Biosys 2020; 4:1900290 [View Article] [PubMed]
     [Google Scholar]
  80. Wang X, Lord DM, Hong SH, Peti W, Benedik MJ et al. Type II toxin/antitoxin MqsR/MqsA controls type V toxin/antitoxin GhoT/GhoS. Environ Microbiol 2013; 15:1734–1744 [View Article] [PubMed]
     [Google Scholar]
  81. Chandra S, Gupta K, Khare S, Kohli P, Asok A et al. The high mutational sensitivity of ccdA antitoxin is linked to codon optimality. Mol Biol Evol 2022; 39:msac187 [View Article] [PubMed]
     [Google Scholar]
  82. Van Melderen L. Toxin-antitoxin systems: why so many, what for?. Curr Opin Microbiol 2010; 13:781–785 [View Article] [PubMed]
     [Google Scholar]
  83. Pecota DC, Wood TK. Exclusion of T4 phage by the hok/sok killer locus from plasmid R1. J Bacteriol 1996; 178:2044–2050 [View Article] [PubMed]
     [Google Scholar]
  84. Song S, Wood TK. A primary physiological role of toxin/antitoxin systems is phage inhibition. Front Microbiol 2020; 11:1895 [View Article] [PubMed]
     [Google Scholar]
  85. Jurėnas D, Fraikin N, Goormaghtigh F, Van Melderen L. Biology and evolution of bacterial toxin-antitoxin systems. Nat Rev Microbiol 2022; 20:335–350 [View Article] [PubMed]
     [Google Scholar]
  86. Li M, Gong L, Cheng F, Yu H, Zhao D et al. Toxin-antitoxin RNA pairs safeguard CRISPR-Cas systems. Science 2021; 372:eabe5601 [View Article] [PubMed]
     [Google Scholar]
  87. Fineran PC, Blower TR, Foulds IJ, Humphreys DP, Lilley KS et al. The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. Proc Natl Acad Sci U S A 2009; 106:894–899 [View Article]
     [Google Scholar]
  88. Bobonis J, Mitosch K, Mateus A, Kritikos G, Elfenbein JR et al. Phage proteins block and trigger retron toxin/antitoxin systems. Microbiology [View Article]
     [Google Scholar]
  89. Vassallo CN, Doering CR, Littlehale ML, Teodoro GIC, Laub MT. A functional selection reveals previously undetected anti-phage defence systems in the E. coli pangenome. Nat Microbiol 2022; 7:1568–1579 [View Article] [PubMed]
     [Google Scholar]
  90. Makarova KS, Wolf YI, Iranzo J, Shmakov SA, Alkhnbashi OS et al. Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants. Nat Rev Microbiol 2020; 18:67–83 [View Article] [PubMed]
     [Google Scholar]
  91. LeRoux M, Srikant S, Teodoro GIC, Zhang T, Littlehale ML et al. The DarTG toxin-antitoxin system provides phage defence by ADP-ribosylating viral DNA. Nat Microbiol 2022; 7:1028–1040 [View Article] [PubMed]
     [Google Scholar]
  92. Otsuka Y, Yonesaki T. Dmd of bacteriophage T4 functions as an antitoxin against Escherichia coli LsoA and RnlA toxins. Mol Microbiol 2012; 83:669–681 [View Article] [PubMed]
     [Google Scholar]
  93. Freire DM, Gutierrez C, Garza-Garcia A, Grabowska AD, Sala AJ et al. An NAD+ phosphorylase toxin triggers Mycobacterium tuberculosis cell death. Mol Cell 2019; 73:1282–1291 [View Article] [PubMed]
     [Google Scholar]
  94. Sberro H, Leavitt A, Kiro R, Koh E, Peleg Y et al. Discovery of functional toxin/antitoxin systems in bacteria by shotgun cloning. Mol Cell 2013; 50:136–148 [View Article] [PubMed]
     [Google Scholar]
  95. Li Y, Liu X, Tang K, Wang W, Guo Y et al. Prophage encoding toxin/antitoxin system PfiT/PfiA inhibits Pf4 production in Pseudomonas aeruginosa. Microb Biotechnol 2020; 13:1132–1144 [View Article] [PubMed]
     [Google Scholar]
  96. Guegler CK, Laub MT. Shutoff of host transcription triggers a toxin-antitoxin system to cleave phage RNA and abort infection. Molecular Cell 2021; 81:2361–2373 [View Article] [PubMed]
     [Google Scholar]
  97. Srikant S, Guegler CK, Laub MT. The evolution of a counter-defense mechanism in a virus constrains its host range. eLife 2022; 11: [View Article] [PubMed]
     [Google Scholar]
  98. Fillol-Salom A, Rostøl JT, Ojiogu AD, Chen J, Douce G et al. Bacteriophages benefit from mobilizing pathogenicity islands encoding immune systems against competitors. Cell 2022; 185:3248–3262 [View Article] [PubMed]
     [Google Scholar]
  99. Tuller T, Kupiec M, Ruppin E, Gerstein MB. Determinants of protein abundance and translation efficiency in S. cerevisiae. PLOS Comput Biol 2007; 3:e248 [View Article] [PubMed]
     [Google Scholar]
  100. Nie L, Wu G, Zhang W. Correlation between mRNA and protein abundance in Desulfovibrio vulgaris: A multiple regression to identify sources of variations. Biochem Biophys Res Commun 2006; 339:603–610 [View Article]
     [Google Scholar]
  101. Freiberg JA, Le Breton Y, Tran BQ, Scott AJ, Harro JM et al. Global analysis and comparison of the transcriptomes and proteomes of group A Streptococcus Biofilms. mSystems 2016; 1:e00149-16 [View Article] [PubMed]
     [Google Scholar]
  102. Taniguchi Y, Choi PJ, Li G-W, Chen H, Babu M et al. Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells. Science 2010; 329:533–538 [View Article] [PubMed]
     [Google Scholar]
  103. Urbanczyk H, Ast JC, Higgins MJ, Carson J, Dunlap PVY. Reclassification of Vibrio fischeri, Vibrio logei, Vibrio salmonicida and Vibrio wodanis as Aliivibrio fischeri gen. nov., comb. nov., Aliivibrio logei comb. nov., Aliivibrio salmonicida comb. nov. and Aliivibrio wodanis comb. nov. Int J Syst Evol Microbiol 2007; 57:2823–2829 [View Article]
     [Google Scholar]
  104. Turovskiy Y, Kashtanov D, Paskhover B, Chikindas ML. Quorum sensing: fact, fiction, and everything in between. Adv Appl Microbiol 2007; 62:191–234 [View Article] [PubMed]
     [Google Scholar]
  105. Henke JM, Bassler BL. Bacterial social engagements. Trends Cell Biol 2004; 14:648–656 [View Article] [PubMed]
     [Google Scholar]
  106. Venturi V. Regulation of quorum sensing in Pseudomonas. FEMS Microbiol Rev 2006; 30:274–291 [View Article] [PubMed]
     [Google Scholar]
  107. Lin J, Cheng J, Wang Y, Shen X. The Pseudomonas quinolone signal (PQS): not just for quorum sensing anymore. Front Cell Infect Microbiol 2018; 8:230 [View Article] [PubMed]
     [Google Scholar]
  108. Gardan R, Besset C, Gitton C, Guillot A, Fontaine L et al. Extracellular life cycle of ComS, the competence-stimulating peptide of Streptococcus thermophilus. J Bacteriol 2013; 195:1845–1855 [View Article] [PubMed]
     [Google Scholar]
  109. Griffith F. The significance of Pneumococcal types. J Hyg (Lond) 1928; 27:113–159 [View Article] [PubMed]
     [Google Scholar]
  110. Håvarstein LS, Coomaraswamy G, Morrison DA. An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae. Proc Natl Acad Sci U S A 1995; 92:11140–11144 [View Article] [PubMed]
     [Google Scholar]
  111. Yang Y, Tal-Gan Y. Exploring the competence stimulating peptide (CSP) N-terminal requirements for effective ComD receptor activation in group1 Streptococcus pneumoniae. Bioorg Chem 2019; 89:102987 [View Article] [PubMed]
     [Google Scholar]
  112. Winzer K, Hardie KR, Williams P. Bacterial cell-to-cell communication: sorry, can’t talk now - gone to lunch!. Curr Opin Microbiol 2002; 5:216–222 [View Article] [PubMed]
     [Google Scholar]
  113. Kim J, Park W. Indole: a signaling molecule or a mere metabolic byproduct that alters bacterial physiology at a high concentration?. J Microbiol 2015; 53:421–428 [View Article] [PubMed]
     [Google Scholar]
  114. Leung V, Dufour D, Lévesque CM. Death and survival in Streptococcus mutans: differing outcomes of a quorum-sensing signaling peptide. Front Microbiol 2015; 6:1176 [View Article] [PubMed]
     [Google Scholar]
  115. Dietrich LEP, Price-Whelan A, Petersen A, Whiteley M, Newman DK. The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa. Mol Microbiol 2006; 61:1308–1321 [View Article] [PubMed]
     [Google Scholar]
  116. Möker N, Dean CR, Tao J. Pseudomonas aeruginosa increases formation of multidrug-tolerant persister cells in response to quorum-sensing signaling molecules. J Bacteriol 2010; 192:1946–1955 [View Article] [PubMed]
     [Google Scholar]
  117. Hall S, McDermott C, Anoopkumar-Dukie S, McFarland AJ, Forbes A et al. Cellular effects of pyocyanin, a secreted virulence factor of Pseudomonas aeruginosa. Toxins (Basel) 2016; 8:236 [View Article]
     [Google Scholar]
  118. Meirelles LA, Newman DK. Both toxic and beneficial effects of pyocyanin contribute to the lifecycle of Pseudomonas aeruginosa. Mol Microbiol 2018; 110:995–1010 [View Article]
     [Google Scholar]
  119. Pu Y, Zhao Z, Li Y, Zou J, Ma Q et al. Enhanced efflux activity facilitates drug tolerance in dormant bacterial cells. Molecular Cell 2016; 62:284–294 [View Article] [PubMed]
     [Google Scholar]
  120. Que Y-A, Hazan R, Strobel B, Maura D, He J et al. A quorum sensing small volatile molecule promotes antibiotic tolerance in bacteria. PLoS ONE 2013; 8:e80140 [View Article]
     [Google Scholar]
  121. Allegretta G, Maurer CK, Eberhard J, Maura D, Hartmann RW et al. In-depth profiling of MvfR-regulated small molecules in Pseudomonas aeruginosa after quorum sensing inhibitor treatment. Front Microbiol 2017; 8:924 [View Article]
     [Google Scholar]
  122. Pan J, Xie X, Tian W, Bahar AA, Lin N et al. (Z)-4-Bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one sensitizes Escherichia coli persister cells to antibiotics. Appl Microbiol Biotechnol 2013; 97:9145–9154 [View Article] [PubMed]
     [Google Scholar]
  123. Pan J, Song F, Ren D. Controlling persister cells of Pseudomonas aeruginosa PDO300 by (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one. Bioorg Med Chem Lett 2013; 23:4648–4651 [View Article] [PubMed]
     [Google Scholar]
  124. Pan J, Bahar AA, Syed H, Ren D. Reverting antibiotic tolerance of Pseudomonas aeruginosa PAO1 persister cells by (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one. PLoS One 2012; 7:e45778 [View Article]
     [Google Scholar]
  125. Schafhauser J, Lepine F, McKay G, Ahlgren HG, Khakimova M et al. The stringent response modulates 4-hydroxy-2-alkylquinoline biosynthesis and quorum-sensing hierarchy in Pseudomonas aeruginosa. J Bacteriol 2014; 196:1641–1650 [View Article] [PubMed]
     [Google Scholar]
  126. Pacios O, Blasco L, Bleriot I, Fernandez-Garcia L, Ambroa A et al. (p)ppGpp and Its Role in Bacterial Persistence: New Challenges. Antimicrob Agents Chemother 2020; 64:e01283-20 [View Article] [PubMed]
     [Google Scholar]
  127. Leung V, Ajdic D, Koyanagi S, Lévesque CM. The formation of Streptococcus mutans persisters induced by the quorum-sensing peptide pheromone is affected by the LexA regulator. J Bacteriol 2015; 197:1083–1094 [View Article] [PubMed]
     [Google Scholar]
  128. Jarosz LM, Deng DM, van der Mei HC, Crielaard W, Krom BP. Streptococcus mutans competence-stimulating peptide inhibits Candida albicans hypha formation. Eukaryot Cell 2009; 8:1658–1664 [View Article]
     [Google Scholar]
  129. Leung V, Lévesque CM. A stress-inducible quorum-sensing peptide mediates the formation of persister cells with noninherited multidrug tolerance. J Bacteriol 2012; 194:2265–2274 [View Article] [PubMed]
     [Google Scholar]
  130. Dufour D, Zhao H, Gong S-G, Lévesque CM. A DNA-damage inducible gene promotes the formation of antibiotic persisters in response to the quorum sensing signaling peptide in Streptococcus mutans. Genes (Basel) 2022; 13:1434 [View Article] [PubMed]
     [Google Scholar]
  131. Shanker E, Federle MJ. Quorum sensing regulation of competence and bacteriocins in Streptococcus pneumoniae and mutans. Genes 2017; 8:15 [View Article]
     [Google Scholar]
  132. Zu Y, Li W, Wang Q, Chen J, Guo Q. ComDE two-component signal transduction systems in oral Streptococci: structure and function. Curr Issues Mol Biol 2019; 32:201–258 [View Article]
     [Google Scholar]
  133. Lee J-H, Lee J. Indole as an intercellular signal in microbial communities. FEMS Microbiol Rev 2010; 34:426–444 [View Article] [PubMed]
     [Google Scholar]
  134. Gaimster H, Cama J, Hernández-Ainsa S, Keyser UF, Summers DK. The indole pulse: a new perspective on indole signalling in Escherichia coli. PLoS One 2014; 9:e93168 [View Article] [PubMed]
     [Google Scholar]
  135. Vega NM, Allison KR, Khalil AS, Collins JJ. Signaling-mediated bacterial persister formation. Nat Chem Biol 2012; 8:431–433 [View Article] [PubMed]
     [Google Scholar]
  136. Lee J-H, Kim Y-G, Gwon G, Wood TK, Lee J. Halogenated indoles eradicate bacterial persister cells and biofilms. AMB Express 2016; 6:123 [View Article] [PubMed]
     [Google Scholar]
  137. Zarkan A, Matuszewska M, Trigg SB, Zhang M, Belgami D et al. Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters. Sci Rep 2020; 10:11742 [View Article] [PubMed]
     [Google Scholar]
  138. Han J-T, Li D-Y, Zhang M-Y, Yu X-Q, Jia X-X et al. EmhR is an indole-sensing transcriptional regulator responsible for the indole-induced antibiotic tolerance in Pseudomonas fluorescens. Environ Microbiol 2021; 23:2054–2069 [View Article] [PubMed]
     [Google Scholar]
  139. Zarkan A, Caño-Muñiz S, Zhu J, Al Nahas K, Cama J et al. Indole pulse signalling regulates the cytoplasmic pH of E. coli in a memory-like manner. Sci Rep 2019; 9:3868 [View Article] [PubMed]
     [Google Scholar]
  140. Chimerel C, Field CM, Piñero-Fernandez S, Keyser UF, Summers DK. Indole prevents Escherichia coli cell division by modulating membrane potential. Biochim Biophys Acta 2012; 1818:1590–1594 [View Article] [PubMed]
     [Google Scholar]
  141. Goode O, Smith A, Zarkan A, Cama J, Invergo BM et al. Persister Escherichia coli cells have a lower intracellular pH than susceptible cells but maintain their pH in response to antibiotic treatment. mBio 2021; 12:e0090921 [View Article] [PubMed]
     [Google Scholar]
  142. Hong SH, Wang X, O’Connor HF, Benedik MJ, Wood TK. Bacterial persistence increases as environmental fitness decreases. Microb Biotechnol 2012; 5:509–522 [View Article] [PubMed]
     [Google Scholar]
  143. Wu N, He L, Cui P, Wang W, Yuan Y et al. Ranking of persister genes in the same Escherichia coli genetic background demonstrates varying importance of individual persister genes in tolerance to different antibiotics. Front Microbiol 2015; 6:1003 [View Article] [PubMed]
     [Google Scholar]
  144. Hu Y, Kwan BW, Osbourne DO, Benedik MJ, Wood TK. Toxin YafQ increases persister cell formation by reducing indole signalling. Environ Microbiol 2015; 17:1275–1285 [View Article] [PubMed]
     [Google Scholar]
  145. Sommerfeldt N, Possling A, Becker G, Pesavento C, Tschowri N et al. Gene expression patterns and differential input into curli fimbriae regulation of all GGDEF/EAL domain proteins in Escherichia coli. Microbiology (Reading) 2009; 155:1318–1331 [View Article] [PubMed]
     [Google Scholar]
  146. Kwan BW, Osbourne DO, Hu Y, Benedik MJ, Wood TK. Phosphodiesterase DosP increases persistence by reducing cAMP which reduces the signal indole. Biotechnol Bioeng 2015; 112:588–600 [View Article] [PubMed]
     [Google Scholar]
  147. Lang M, Krin E, Korlowski C, Sismeiro O, Varet H et al. Sleeping ribosomes: bacterial signaling triggers RaiA mediated persistence to aminoglycosides. iScience 2021; 24:103128 [View Article] [PubMed]
     [Google Scholar]
  148. Xu T, Wang X-Y, Cui P, Zhang Y-M, Zhang W-H et al. The Agr quorum sensing system represses persister formation through regulation of phenol soluble modulins in Staphylococcus aureus. Front Microbiol 2017; 8:2189 [View Article] [PubMed]
     [Google Scholar]
  149. Personnic N, Striednig B, Hilbi H. Quorum sensing controls persistence, resuscitation, and virulence of Legionella subpopulations in biofilms. ISME J 2021; 15:196–210 [View Article] [PubMed]
     [Google Scholar]
  150. Song S, Wood TK. Combatting persister cells with substituted indoles. Front Microbiol 2020; 11:1565 [View Article] [PubMed]
     [Google Scholar]
  151. Tomberlin JK, Crippen TL, Wu G, Griffin AS, Wood TK et al. Indole: an evolutionarily conserved influencer of behavior across kingdoms. Bioessays 2017; 39:1600203 [View Article] [PubMed]
     [Google Scholar]
  152. Darkoh C, Plants-Paris K, Bishoff D, DuPont HL. Clostridium difficile modulates the gut microbiota by inducing the production of indole, an interkingdom signaling and antimicrobial molecule. mSystems 2019; 4:e00346-18 [View Article]
     [Google Scholar]
  153. Vega NM, Allison KR, Samuels AN, Klempner MS, Collins JJ. Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance. Proc Natl Acad Sci U S A 2013; 110:14420–14425 [View Article]
     [Google Scholar]
  154. Chu W, Zere TR, Weber MM, Wood TK, Whiteley M et al. Indole production promotes Escherichia coli mixed-culture growth with Pseudomonas aeruginosa by inhibiting quorum signaling. Appl Environ Microbiol 2012; 78:411–419 [View Article]
     [Google Scholar]
  155. Wang Y, Li H, Cui X, Zhang X-H. A novel stress response mechanism, triggered by indole, involved in quorum quenching enzyme MomL and iron-sulfur cluster in Muricauda olearia Th120. Sci Rep 2017; 7:4252 [View Article] [PubMed]
     [Google Scholar]
  156. Kim J, Park W. Indole inhibits bacterial quorum sensing signal transmission by interfering with quorum sensing regulator folding. Microbiology (Reading) 2013; 159:2616–2625 [View Article] [PubMed]
     [Google Scholar]
  157. Rahman P, Pasirayi G, Auger V, Ali Z. Development of a simple and low cost microbioreactor for high-throughput bioprocessing. Biotechnol Lett 2009; 31:209–214 [View Article] [PubMed]
     [Google Scholar]
  158. Bhargava N, Sharma P, Capalash N. Pyocyanin stimulates quorum sensing-mediated tolerance to oxidative stress and increases persister cell populations in Acinetobacter baumannii. Infect Immun 2014; 82:3417–3425 [View Article] [PubMed]
     [Google Scholar]
  159. McCready AR, Paczkowski JE, Henke BR, Bassler BL. Structural determinants driving homoserine lactone ligand selection in the Pseudomonas aeruginosa LasR quorum-sensing receptor. Proc Natl Acad Sci USA 2019; 116:245–254 [View Article]
     [Google Scholar]
  160. Cabuhat KSP, Moron-Espiritu LS. Quorum sensing orchestrates antibiotic drug resistance, biofilm formation, and motility in Escherichia coli and quorum quenching activities of plant-derived natural products: a review. J Pure Appl Microbiol 2022; 16:1538–1549 [View Article]
     [Google Scholar]
  161. Lee J, Maeda T, Hong SH, Wood TK. Reconfiguring the quorum-sensing regulator SdiA of Escherichia coli to control biofilm formation via indole and N-acylhomoserine lactones. Appl Environ Microbiol 2009; 75:1703–1716 [View Article] [PubMed]
     [Google Scholar]
  162. Culler HF, Couto SCF, Higa JS, Ruiz RM, Yang MJ et al. Role of SdiA on biofilm formation by atypical enteropathogenic Escherichia coli. Genes (Basel) 2018; 9:253 [View Article] [PubMed]
     [Google Scholar]
  163. Yan J, Bassler BL. Surviving as a community: antibiotic tolerance and persistence in bacterial biofilms. Cell Host Microbe 2019; 26:15–21 [View Article] [PubMed]
     [Google Scholar]
  164. Day T. Interpreting phenotypic antibiotic tolerance and persister cells as evolution via epigenetic inheritance. Mol Ecol 2016; 25:1869–1882 [View Article] [PubMed]
     [Google Scholar]
  165. Hingley-Wilson SM, Ma N, Hu Y, Casey R, Bramming A et al. Loss of phenotypic inheritance associated with ydcI mutation leads to increased frequency of small, slow persisters in Escherichia coli. Proc Natl Acad Sci U S A 2020; 117:4152–4157 [View Article]
     [Google Scholar]
  166. Xu Y, Liu S, Zhang Y, Zhang W. Role of DNA methylation in persister formation in uropathogenic E. coli. Microbiology 2020 [View Article]
     [Google Scholar]
  167. Ghosh D, Veeraraghavan B, Elangovan R, Vivekanandan P. Antibiotic resistance and epigenetics: more to it than meets the eye. Antimicrob Agents Chemother 2020; 64: [View Article]
     [Google Scholar]
  168. Muhammad JS, Khan NA, Maciver SK, Alharbi AM, Alfahemi H et al. Epigenetic-mediated antimicrobial resistance: host versus pathogen epigenetic alterations. Antibiotics (Basel) 2022; 11:809 [View Article]
     [Google Scholar]
  169. Levin-Reisman I, Balaban NQ. Quantitative measurements of type I and type II persisters using scanlag. Methods Mol Biol 2016; 1333:75–81 [View Article] [PubMed]
     [Google Scholar]
  170. Eling N, Morgan MD, Marioni JC. Challenges in measuring and understanding biological noise. Nat Rev Genet 2019; 20:536–548 [View Article] [PubMed]
     [Google Scholar]
  171. Feng J, Kessler DA, Ben-Jacob E, Levine H. Growth feedback as a basis for persister bistability. Proc Natl Acad Sci U S A 2014; 111:544–549 [View Article]
     [Google Scholar]
  172. Nicolau SE, Lewis K. The role of integration host factor in Escherichia coli persister formation. mBio 2022; 13:e0342021 [View Article]
     [Google Scholar]
  173. Zalis EA, Nuxoll AS, Manuse S, Clair G, Radlinski LC et al. stochastic variation in expression of the tricarboxylic acid cycle produces persister cells. mBio 2019; 10:e01930-19 [View Article]
     [Google Scholar]
  174. Sureka K, Ghosh B, Dasgupta A, Basu J, Kundu M et al. Positive feedback and noise activate the stringent response regulator rel in mycobacteria. PLoS One 2008; 3:e1771 [View Article] [PubMed]
     [Google Scholar]
  175. Zorzan I, Del Favero S, Giaretta A, Manganelli R, Di Camillo B et al. Mathematical modelling of SigE regulatory network reveals new insights into bistability of mycobacterial stress response. BMC Bioinformatics 2021; 22:558 [View Article] [PubMed]
     [Google Scholar]
  176. Boldrin F, Provvedi R, Cioetto Mazzabò L, Segafreddo G, Manganelli R. Tolerance and persistence to drugs: a main challenge in the fight against Mycobacterium tuberculosis. Front Microbiol 2020; 11:1924 [View Article] [PubMed]
     [Google Scholar]
  177. Quigley J, Lewis K. Noise in a metabolic pathway leads to persister formation in Mycobacterium tuberculosis. Microbiol Spectr 2022; 10:e0294822 [View Article] [PubMed]
     [Google Scholar]
  178. Hahn J, Tanner AW, Carabetta VJ, Cristea IM, Dubnau D. ComGA-RelA interaction and persistence in the Bacillus subtilis K-state. Mol Microbiol 2015; 97:454–471 [View Article] [PubMed]
     [Google Scholar]
  179. Wood TK, Song S. Forming and waking dormant cells: The ppGpp ribosome dimerization persister model. Biofilm 2020; 2:100018 [View Article] [PubMed]
     [Google Scholar]
  180. Goormaghtigh F, Van Melderen L. 2016 Optimized Method for Measuring Persistence in Escherichia coli with Improved Reproducibility. 43–52 Michiels J, Fauvart M. Bacterial Persistence Springer; New York, New York, NY:
     [Google Scholar]
  181. Cama J, Pagliara S. Microfluidic single-cell phenotyping of the activity of peptide-based antimicrobials. Methods Mol Biol 2021; 2208:237–253 [View Article] [PubMed]
     [Google Scholar]
  182. Bamford RA, Smith A, Metz J, Glover G, Titball RW et al. Investigating the physiology of viable but non-culturable bacteria by microfluidics and time-lapse microscopy. BMC Biol 2017; 15:121 [View Article] [PubMed]
     [Google Scholar]
  183. Goode O, Smith A, Łapińska U, Bamford R, Kahveci Z et al. Heterologous protein expression favors the formation of protein aggregates in persister and viable but nonculturable bacteria. ACS Infect Dis 2021; 7:1848–1858 [View Article] [PubMed]
     [Google Scholar]
  184. Stuck AK, Täuber MG, Schabel M, Lehmann T, Suter H et al. Determinants of quinolone versus trimethoprim-sulfamethoxazole use for outpatient urinary tract infection. Antimicrob Agents Chemother 2012; 56:1359–1363 [View Article] [PubMed]
     [Google Scholar]
  185. Aas JA, Griffen AL, Dardis SR, Lee AM, Olsen I et al. Bacteria of dental caries in primary and permanent teeth in children and young adults. J Clin Microbiol 2008; 46:1407–1417 [View Article] [PubMed]
     [Google Scholar]
  186. Cheng L, Zhang L, Yue L, Ling J, Fan M et al. Expert consensus on dental caries management. Int J Oral Sci 2022; 14:17 [View Article] [PubMed]
     [Google Scholar]
  187. Gu H-J, Sun Q-L, Luo J-C, Zhang J, Sun L. A first study of the virulence potential of A Bacillus subtilis isolate from deep-sea hydrothermal vent. Front Cell Infect Microbiol 2019; 9:183 [View Article] [PubMed]
     [Google Scholar]
  188. T JAS, J R, Rajan A, Shankar V. Features of the biochemistry of Mycobacterium smegmatis, as a possible model for Mycobacterium tuberculosis. J Infect Public Health 2020; 13:1255–1264 [View Article] [PubMed]
     [Google Scholar]
  189. West TE, Frevert CW, Liggitt HD, Skerrett SJ. Inhalation of Burkholderia thailandensis results in lethal necrotizing pneumonia in mice: a surrogate model for pneumonic melioidosis. Trans R Soc Trop Med Hyg 2008; 102 Suppl 1:S119–26 [View Article]
     [Google Scholar]
  190. Scales BS, Dickson RP, LiPuma JJ, Huffnagle GB. Microbiology, genomics, and clinical significance of the Pseudomonas fluorescens species complex, an unappreciated colonizer of humans. Clin Microbiol Rev 2014; 27:927–948 [View Article] [PubMed]
     [Google Scholar]
  191. Park SB, Aoki T, Jung TS. Pathogenesis of and strategies for preventing Edwardsiella tarda infection in fish. Vet Res 2012; 43:67 [View Article] [PubMed]
     [Google Scholar]
  192. Zeng Y, Liu B. Self-propelling and rolling of a sessile-motile aggregate of the bacterium Caulobacter crescentus. Commun Biol 2020; 3:1–8 [View Article]
     [Google Scholar]
  193. Singh S, Bhatia S. Quorum sensing inhibitors: curbing pathogenic infections through inhibition of bacterial communication. Iran J Pharm Res 2021; 20:486–514 [View Article] [PubMed]
     [Google Scholar]
  194. Rada B, Leto TL. Pyocyanin effects on respiratory epithelium: relevance in Pseudomonas aeruginosa airway infections. Trends Microbiol 2013; 21:73–81 [View Article] [PubMed]
     [Google Scholar]
  195. Uruén C, Chopo-Escuin G, Tommassen J, Mainar-Jaime RC, Arenas J. Biofilms as promoters of bacterial antibiotic resistance and tolerance. Antibiotics (Basel) 2020; 10:3 [View Article] [PubMed]
     [Google Scholar]
  196. Hauryliuk V, Atkinson GC, Murakami KS, Tenson T, Gerdes K. Recent functional insights into the role of (p)ppGpp in bacterial physiology. Nat Rev Microbiol 2015; 13:298–309 [View Article] [PubMed]
     [Google Scholar]
  197. Zhang S-P, Wang Q, Quan S-W, Yu X-Q, Wang Y et al. Type II toxin–antitoxin system in bacteria: activation, function, and mode of action. Biophys Rep 2020; 6:68–79 [View Article]
     [Google Scholar]
  198. Rycroft JA, Gollan B, Grabe GJ, Hall A, Cheverton AM et al. Activity of acetyltransferase toxins involved in Salmonella persister formation during macrophage infection. Nat Commun 2018; 9:1993 [View Article] [PubMed]
     [Google Scholar]
  199. Walling LR, Butler JS. Homologous VapC toxins inhibit translation and cell growth by sequence-specific cleavage of tRNAfMet. J Bacteriol 2018; 200:e00582-17 [View Article] [PubMed]
     [Google Scholar]
  200. Germain E, Castro-Roa D, Zenkin N, Gerdes K. Molecular mechanism of bacterial persistence by HipA. Mol Cell 2013; 52:248–254 [View Article] [PubMed]
     [Google Scholar]
  201. Han Y, Lee E-J. Substrate specificity of bacterial endoribonuclease toxins. BMB Rep 2020; 53:611–621 [PubMed]
     [Google Scholar]
  202. Jiang Y, Pogliano J, Helinski DR, Konieczny I. ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyrase. Mol Microbiol 2002; 44:971–979 [View Article] [PubMed]
     [Google Scholar]
  203. Cook GM, Robson JR, Frampton RA, McKenzie J, Przybilski R et al. Ribonucleases in bacterial toxin-antitoxin systems. Biochim Biophys Acta 2013; 1829:523–531 [View Article]
     [Google Scholar]
  204. Butt A, Higman VA, Williams C, Crump MP, Hemsley CM et al. The HicA toxin from Burkholderia pseudomallei has a role in persister cell formation. Biochem J 2014; 459:333–344 [View Article] [PubMed]
     [Google Scholar]
  205. Dörr T, Vulić M, Lewis K. 2010; Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli. PLOS Biology 8:e1000317
     [Google Scholar]
  206. Schütz C, Empting M. Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers. Beilstein J Org Chem 2018; 14:2627–2645 [View Article] [PubMed]
     [Google Scholar]
  207. Whiteley M, Diggle SP, Greenberg EP. Progress in and promise of bacterial quorum sensing research. Nature 2017; 551:313–320 [View Article] [PubMed]
     [Google Scholar]
  208. Ding F, Oinuma K-I, Smalley NE, Schaefer AL, Hamwy O et al. The Pseudomonas aeruginosa Orphan Quorum Sensing Signal Receptor QscR Regulates Global Quorum Sensing Gene Expression by Activating a Single Linked Operon. mBio 2018; 9:mBio [View Article] [PubMed]
     [Google Scholar]
  209. Groleau M-C, de Oliveira Pereira T, Dekimpe V, Déziel E, Shank EA et al. PqsE Is essential for RhlR-dependent quorum sensing regulation in Pseudomonas aeruginosa. mSystems 2020; 5: [View Article] [PubMed]
     [Google Scholar]
  210. Carloni S, Macchi R, Sattin S, Ferrara S, Bertoni G. The small RNA ReaL: a novel regulatory element embedded in the Pseudomonas aeruginosa quorum sensing networks. Environmental Microbiology 2017; 19:4220–4237 [View Article] [PubMed]
     [Google Scholar]
  211. Lee J, Zhang L. The hierarchy quorum sensing network in Pseudomonas aeruginosa. Protein Cell 2015; 6:26–41 [View Article] [PubMed]
     [Google Scholar]
  212. Chugani SA, Whiteley M, Lee KM, D’Argenio D, Manoil C, Greenberg EP. 2001; QscR, a modulator of quorum-sensing signal synthesis and virulence in Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences 98:2752–2757
     [Google Scholar]
  213. Duplantier M, Lohou E, Sonnet P. Quorum sensing inhibitors to quench P. aeruginosa pathogenicity. Pharmaceuticals (Basel) 2021; 14:1262 [View Article]
     [Google Scholar]
  214. Leung V, Ajdic D, Koyanagi S, Lévesque CM. The formation of Streptococcus mutans persisters induced by the quorum-sensing peptide pheromone is affected by the LexA regulator. J Bacteriol 2015; 197:1083–1094 [View Article] [PubMed]
     [Google Scholar]
  215. Wang S, Zhao C, Xue B, Li C, Zhang X et al. Nanoalumina triggers the antibiotic persistence of Escherichia coli through quorum sensing regulators lrsF and qseB. J Hazard Mater 2022; 436:129198 [View Article] [PubMed]
     [Google Scholar]
  216. Denham JD, Nanjappa S, Greene JN. Treatment of Enteropathogenic Escherichia coli diarrhea in cancer patients: a series of three cases. Case Rep Infect Dis 2018; 2018:8438701 [View Article] [PubMed]
     [Google Scholar]
  217. Overview | Urinary tract infection (lower): antimicrobial prescribing | Guidance | NICE. NICE; n.d https://www.nice.org.uk/guidance/ng109 accessed 16 August 2022
  218. Wu W, Jin Y, Bai F, Jin S. Chapter 41 - Pseudomonas aeruginosa. In Tang Y-W, Sussman M, Liu D, Poxton I, Schwartzman J. eds Molecular Medical Microbiology, Second Edition. Boston: Academic Press; 2015 pp 753–767
     [Google Scholar]
  219. Langton Hewer SC, Smyth AR. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev 2017; 4:CD004197 [View Article] [PubMed]
     [Google Scholar]
  220. Banerjee D, Stableforth D. The treatment of respiratory Pseudomonas infection in cystic fibrosis: what drug and which way?. Drugs 2000; 60:1053–1064 [View Article] [PubMed]
     [Google Scholar]
  221. David MZ, Daum RS. Treatment of Staphylococcus aureus Infections. In Bagnoli F, Rappuoli R, Grandi G. eds Staphylococcus Aureus: Microbiology, Pathology, Immunology, Therapy and Prophylaxis Cham: Springer International Publishing; 2017 pp 325–383
     [Google Scholar]
  222. Lee E, Anjum F. Staphylococcus Epidermidis Treasure Island (FL): StatPearls Publishing; 2022
     [Google Scholar]
  223. Ashurst JV, Dawson A. Klebsiella Pneumonia Treasure Island (FL): StatPearls Publishing; 2022
     [Google Scholar]
  224. Trecarichi EM, Pagano L, Martino B, Candoni A, Di Blasi R et al. Bloodstream infections caused by klebsiella pneumoniae in onco-hematological patients: clinical impact of carbapenem resistance in a multicentre prospective survey. Am J Hematol 2016; 91:1076–1081 [View Article]
     [Google Scholar]
  225. Wei M, Yongjie Z, Zhuoyu Q, Biao Y, Xi J et al. Pneumonia caused by Mycobacterium tuberculosis. Microbes Infect 2020; 22:278–284 [View Article]
     [Google Scholar]
  226. Ajmera A, Shabbir N. SalmonellaStatPearls Treasure Island (FL): StatPearls Publishing; 2022
     [Google Scholar]
  227. Ross BN, Myers JN, Muruato LA, Tapia D, Torres AG. Evaluating new compounds to treat Burkholderia pseudomallei Infections. Front Cell Infect Microbiol 2018; 8: [View Article] [PubMed]
     [Google Scholar]
  228. Scoffone VC, Chiarelli LR, Trespidi G, Mentasti M, Riccardi G et al. Burkholderia cenocepacia infections in cystic fibrosis patients: drug resistance and therapeutic approaches. Front Microbiol 2017; 8:1592 [View Article] [PubMed]
     [Google Scholar]
  229. Kanwal S, Vaitla P. Streptococcus Pyogenes StatPearls Publishing, Treasure Island (FL); 2022
     [Google Scholar]
  230. Summary of the evidence | Pneumonia (community-acquired): antimicrobial prescribing | Guidance | NICE. NICE; n.d https://www.nice.org.uk/guidance/ng138/chapter/summary-of-the-evidence accessed 23 August 2022
  231. Michalopoulos A, Falagas ME. Treatment of Acinetobacter infections. Expert Opin Pharmacother 2010; 11:779–788 [View Article] [PubMed]
     [Google Scholar]
  232. Recommendations | clostridioides difficile infection: antimicrobial prescribing | guidance | NICE. NICE; n.d https://www.nice.org.uk/guidance/ng199/chapter/Recommendations#choice-of-antibiotic accessed 22 August 2022
  233. Antibiotic Treatment | Treatment | Cholera | CDC; 2022 https://www.cdc.gov/cholera/treatment/antibiotic-treatment.html accessed 22 August 2022
  234. Arget M, Kosar J, Suen B, Peermohamed S. Successful treatment of Legionnaires’ disease with tigecycline in an immunocompromised man with a legion of antibiotic allergies. Cureus 2019; 11:e4577 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.001266
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Bacterial survivors: evaluating the mechanisms of antibiotic persistence
Microbiology 168, 001266 (2022); https://doi.org/10.1099/mic.0.001266
/content/journal/micro/10.1099/mic.0.001266
/content/journal/micro/10.1099/mic.0.001266
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