Skip to content
1887

Abstract

With a limited number of traditional virulence factors, the success of the nosocomial pathogen is largely attributed to its ability to persist and resist. The niches encountered during infection vary significantly from the more commonly studied laboratory setting, and consequently, the genes responsible for pathogenesis have yet to be fully elucidated. This study utilized the AB5075-UW transposon mutant library with unbiased genome-wide transposon sequencing to identify the genetic basis for survival and fitness during pneumonia and septicaemia infections. We identified 128 genes essential for in-host survival, including 22 required for survival in all tissues. Additionally, 302 genes with significantly altered fitness were also identified. Tissue specificity was observed, highlighting the importance of genes associated with biosynthesis in the lungs, cell shape and structure in the kidneys and metal acquisition during septicaemia. The majority (89%) of the genes with aberrant fitness were constituents of the core genome. The findings were validated using a subset of targeted mutants, including those required for infection (, and ) or specifically septicaemia (, and ) or pneumonia (, and ), confirming that these observations were a result of specific fitness defects rather than aberrant growth. Taken together, these data provide the first global profile of genes required for fitness of during different disease states and growth in different tissues.

Funding
This study was supported by the:
  • National Natural Science Foundation of China (Award 82072344)
    • Principal Award Recipient: YingFu
  • Australian Research Council (Award DE200101524)
    • Principal Award Recipient: FrancescaShort
  • National Health and Medical Research Council (Award 2003416)
    • Principal Award Recipient: AntonY Peleg
  • National Health and Medical Research Council (Award APP1124917)
    • Principal Award Recipient: AntonY Peleg
  • 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.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.001556
2025-11-11
2025-12-16

Metrics

Loading full text...

Full text loading...

/deliver/fulltext/mgen/11/11/mgen001556.html?itemId=/content/journal/mgen/10.1099/mgen.0.001556&mimeType=html&fmt=ahah

References

  1. Martín-Aspas A, Guerrero-Sánchez FM, García-Colchero F, Rodríguez-Roca S, Girón-González J-A. Differential characteristics of Acinetobacter baumannii colonization and infection: risk factors, clinical picture, and mortality. Infect Drug Resist 2018; 11:861–872 [View Article] [PubMed]
    [Google Scholar]
  2. Shadan A, Pathak A, Ma Y, Pathania R, Singh RP. Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infection. Front Cell Infect Microbiol 2023; 13:1053968 [View Article] [PubMed]
    [Google Scholar]
  3. Short FL, Liu Q, Shah B, Clift HE, Naidu V et al. The Acinetobacter baumannii disinfectant resistance protein, AmvA, is a spermidine and spermine efflux pump. Commun Biol 2021; 4:1114 [View Article] [PubMed]
    [Google Scholar]
  4. Castanheira M, Mendes RE, Gales AC. Global epidemiology and mechanisms of resistance of Acinetobacter baumannii-calcoaceticus complex. Clin Infect Dis 2023; 76:S166–S178 [View Article] [PubMed]
    [Google Scholar]
  5. Hoang Quoc C, Nguyen Thi Phuong T, Nguyen Duc H, Tran Le T, Tran Thi Thu H et al. Carbapenemase genes and multidrug resistance of Acinetobacter Baumannii: a cross sectional study of patients with pneumonia in Southern Vietnam. Antibiotics (Basel) 2019; 8:148 [View Article] [PubMed]
    [Google Scholar]
  6. Spellberg B, Rex JH. The value of single-pathogen antibacterial agents. Nat Rev Drug Discov 2013; 12:963 [View Article] [PubMed]
    [Google Scholar]
  7. Shlaes DM, Bradford PA. Antibiotics—from there to where?. PAI 2018; 3:19 [View Article]
    [Google Scholar]
  8. Morris FC, Dexter C, Kostoulias X, Uddin MI, Peleg AY. The Mechanisms of Disease Caused by Acinetobacter baumannii. Front Microbiol 2019; 10:1601 [View Article] [PubMed]
    [Google Scholar]
  9. Barquist L, Boinett CJ, Cain AK. Approaches to querying bacterial genomes with transposon-insertion sequencing. RNA Biol 2013; 10:1161–1169 [View Article] [PubMed]
    [Google Scholar]
  10. Kwon YM, Ricke SC, Mandal RK. Transposon sequencing: methods and expanding applications. Appl Microbiol Biotechnol 2016; 100:31–43 [View Article] [PubMed]
    [Google Scholar]
  11. Cain AK, Barquist L, Goodman AL, Paulsen IT, Parkhill J et al. A decade of advances in transposon-insertion sequencing. Nat Rev Genet 2020; 21:526–540 [View Article] [PubMed]
    [Google Scholar]
  12. Goodall ECA, Robinson A, Johnston IG, Jabbari S, Turner KA et al. The essential genome of Escherichia coli k-12. mBio 2018; 9:e02096–17 [View Article]
    [Google Scholar]
  13. Chaudhuri RR, Morgan E, Peters SE, Pleasance SJ, Hudson DL et al. Comprehensive assignment of roles for Salmonella typhimurium genes in intestinal colonization of food-producing animals. PLoS Genet 2013; 9:e1003456 [View Article] [PubMed]
    [Google Scholar]
  14. Poulsen BE, Yang R, Clatworthy AE, White T, Osmulski SJ et al. Defining the core essential genome of Pseudomonas aeruginosa. Proc Natl Acad Sci USA 2019; 116:10072–10080 [View Article]
    [Google Scholar]
  15. Kim G-L, Hooven TA, Norambuena J, Li B, Boyd JM et al. Growth and stress tolerance comprise independent metabolic strategies critical for Staphylococcus aureus Infection. mBio 2021; 12:e0081421 [View Article] [PubMed]
    [Google Scholar]
  16. Matthews AJ, Rowe HM, Rosch JW, Camilli A. A Tn-seq screen of Streptococcus pneumoniae uncovers dna repair as the major pathway for desiccation tolerance and transmission. Infect Immun 2021; 89:e0071320 [View Article]
    [Google Scholar]
  17. Gebhardt MJ, Gallagher LA, Jacobson RK, Usacheva EA, Peterson LR et al. Joint transcriptional control of virulence and resistance to antibiotic and environmental stress in Acinetobacter baumannii. mBio 2015; 6:e01660–15 [View Article]
    [Google Scholar]
  18. Sanchez-Larrayoz AF, Elhosseiny NM, Chevrette MG, Fu Y, Giunta P et al. Complexity of complement resistance factors expressed by Acinetobacter baumannii needed for survival in human serum. The Journal of Immunology 2017; 199:2803–2814 [View Article]
    [Google Scholar]
  19. Subashchandrabose S, Smith S, DeOrnellas V, Crepin S, Kole M et al. Acinetobacter baumannii genes required for bacterial survival during bloodstream infection. mSphere 2016; 1: [View Article]
    [Google Scholar]
  20. Wang N, Ozer EA, Mandel MJ, Hauser AR. Genome-wide identification of Acinetobacter baumannii genes necessary for persistence in the lung. mBio 2014; 5:e01163–14 [View Article]
    [Google Scholar]
  21. Jacobs AC, Thompson MG, Black CC, Kessler JL, Clark LP et al. AB5075, a highly virulent isolate of Acinetobacter baumannii, as a model strain for the evaluation of pathogenesis and antimicrobial treatments. mBio 2014; 5:e01076-14 [View Article] [PubMed]
    [Google Scholar]
  22. Gallagher LA, Ramage E, Weiss EJ, Radey M, Hayden HS et al. Resources for genetic and genomic analysis of emerging pathogen Acinetobacter baumannii. J Bacteriol 2015; 197:2027–2035 [View Article] [PubMed]
    [Google Scholar]
  23. Harris G, Kuo Lee R, Lam CK, Kanzaki G, Patel GB et al. A mouse model of Acinetobacter baumannii-associated pneumonia using a clinically isolated hypervirulent strain. Antimicrob Agents Chemother 2013; 57:3601–3613 [View Article] [PubMed]
    [Google Scholar]
  24. Morris FC, Jiang Y, Fu Y, Kostoulias X, Murray GL et al. Lactate metabolism promotes in vivo fitness during Acinetobacter baumannii infection. FEMS Microbiol Lett 2024; 371:fnae032 [View Article] [PubMed]
    [Google Scholar]
  25. Barquist L, Mayho M, Cummins C, Cain AK, Boinett CJ et al. The TraDIS toolkit: sequencing and analysis for dense transposon mutant libraries. Bioinformatics 2016; 32:1109–1111 [View Article] [PubMed]
    [Google Scholar]
  26. Andrews S. FastQC: a quality control tool for high throughput sequence data; 2010
  27. Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet j 2011; 17:10 [View Article]
    [Google Scholar]
  28. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010; 26:139–140 [View Article] [PubMed]
    [Google Scholar]
  29. Huerta-Cepas J, Forslund K, Coelho LP, Szklarczyk D, Jensen LJ et al. Fast genome-wide functional annotation through orthology assignment by eggNOG-mapper. Mol Biol Evol 2017; 34:2115–2122 [View Article] [PubMed]
    [Google Scholar]
  30. Alexa A. Gene set enrichment analysis. Encycl Syst Biol 2013806 [View Article]
    [Google Scholar]
  31. Tonkin-Hill G, MacAlasdair N, Ruis C, Weimann A, Horesh G et al. Producing polished prokaryotic pangenomes with the panaroo pipeline. Genome Biol 2020; 21:180 [View Article] [PubMed]
    [Google Scholar]
  32. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  33. Tipton KA, Rather PN. Extraction and Visualization of Capsular Polysaccharide from Acinetobacter baumannii. In Biswas I, Rather PN. eds Acinetobacter Baumannii: Methods and Protocols New York, NY: Springer New York; 2019 pp 227–231
    [Google Scholar]
  34. Haufroid M, Wouters J. Targeting the serine pathway: a promising approach against tuberculosis?. Pharmaceuticals (Basel) 2019; 12:66 [View Article] [PubMed]
    [Google Scholar]
  35. Endo A, Hamamoto H, Oshima K. Serine and purine synthesis pathways are involved in the virulence of Burkholderia gladioli, the causative agent of gladiolus rot. J Gen Plant Pathol 2022; 88:55–62 [View Article]
    [Google Scholar]
  36. Révora V, Marchesini MI, Comerci DJ. Brucella abortus depends on l-serine biosynthesis for intracellular proliferation. Infect Immun 2020; 88:00840–19 [View Article] [PubMed]
    [Google Scholar]
  37. Yang D-X, Yang M-J, Yin Y, Kou T-S, Peng L-T et al. Serine metabolism tunes immune responses to promote Oreochromis niloticus survival upon Edwardsiella tarda infection. mSystems 2021; 6:e0042621 [View Article] [PubMed]
    [Google Scholar]
  38. Fuchs EL, Brutinel ED, Jones AK, Fulcher NB, Urbanowski ML et al. The Pseudomonas aeruginosa Vfr regulator controls global virulence factor expression through cyclic AMP-dependent and -independent mechanisms. J Bacteriol 2010; 192:3553–3564 [View Article] [PubMed]
    [Google Scholar]
  39. Giles SK, Stroeher UH, Eijkelkamp BA, Brown MH. Identification of genes essential for pellicle formation in Acinetobacter baumannii. BMC Microbiol 2015; 15:116 [View Article] [PubMed]
    [Google Scholar]
  40. Penesyan A, Nagy SS, Kjelleberg S, Gillings MR, Paulsen IT. Rapid microevolution of biofilm cells in response to antibiotics. NPJ Biofilms Microbiomes 2019; 5:34 [View Article] [PubMed]
    [Google Scholar]
  41. Harkova LG, de Dios R, Rubio-Valle A, Pérez-Pulido AJ, McCarthy RR. Cyclic AMP is a global virulence regulator governing inter and intrabacterial signalling in Acinetobacter baumannii. PLOS Pathog 2024; 20:e1012529 [View Article] [PubMed]
    [Google Scholar]
  42. Bruchmann S, Feltwell T, Parkhill J, Short FL. Identifying virulence determinants of multidrug-resistant Klebsiella pneumoniae in Galleria mellonella. Pathog Dis 2021; 79:ftab009 [View Article] [PubMed]
    [Google Scholar]
  43. Ikai H, Yamamoto S. Identification and analysis of a gene encoding L-2,4-diaminobutyrate:2-ketoglutarate 4-aminotransferase involved in the 1,3-diaminopropane production pathway in Acinetobacter baumannii. J Bacteriol 1997; 179:5118–5125 [View Article] [PubMed]
    [Google Scholar]
  44. Armalytė J, Čepauskas A, Šakalytė G, Martinkus J, Skerniškytė J et al. A polyamine acetyltransferase regulates the motility and biofilm formation of Acinetobacter baumannii. Nat Commun 2023; 14:3531 [View Article] [PubMed]
    [Google Scholar]
  45. Shah P, Swiatlo E. A multifaceted role for polyamines in bacterial pathogens. Mol Microbiol 2008; 68:4–16 [View Article] [PubMed]
    [Google Scholar]
  46. Skiebe E, de Berardinis V, Morczinek P, Kerrinnes T, Faber F et al. Surface-associated motility, a common trait of clinical isolates of Acinetobacter baumannii, depends on 1,3-diaminopropane. Int J Med Microbiol 2012; 302:117–128 [View Article] [PubMed]
    [Google Scholar]
  47. Kim JS, Choi SH, Lee JK. Lysine decarboxylase expression by Vibrio vulnificus is induced by SoxR in response to superoxide stress. J Bacteriol 2006; 188:8586–8592 [View Article] [PubMed]
    [Google Scholar]
  48. Yoshida M, Kashiwagi K, Shigemasa A, Taniguchi S, Yamamoto K et al. A unifying model for the role of polyamines in bacterial cell growth, the polyamine modulon. J Biol Chem 2004; 279:46008–46013 [View Article] [PubMed]
    [Google Scholar]
  49. Terui Y, Higashi K, Taniguchi S, Shigemasa A, Nishimura K et al. Enhancement of the synthesis of RpoN, Cra, and H-NS by polyamines at the level of translation in Escherichia coli cultured with glucose and glutamate. J Bacteriol 2007; 189:2359–2368 [View Article] [PubMed]
    [Google Scholar]
  50. Iyer R, Wu Z, Woster PM, Delcour AH. Molecular basis for the polyamine-ompF porin interactions: inhibitor and mutant studies. J Mol Biol 2000; 297:933–945 [View Article] [PubMed]
    [Google Scholar]
  51. de Mattos CD, Faith DR, Nemudryi AA, Schmidt AK, Bublitz DC et al. Polyamines and linear DNA mediate bacterial threat assessment of bacteriophage infection. Proc Natl Acad Sci USA 2023; 120:e2216430120 [View Article] [PubMed]
    [Google Scholar]
  52. Ware D, Jiang Y, Lin W, Swiatlo E. Involvement of potD in Streptococcus pneumoniae polyamine transport and pathogenesis. Infect Immun 2006; 74:352–361 [View Article] [PubMed]
    [Google Scholar]
  53. Armbruster CE, Forsyth VS, Johnson AO, Smith SN, White AN et al. Twin arginine translocation, ammonia incorporation, and polyamine biosynthesis are crucial for Proteus mirabilis fitness during bloodstream infection. PLOS Pathog 2019; 15:e1007653 [View Article] [PubMed]
    [Google Scholar]
  54. Sobe RC, Bond WG, Wotanis CK, Zayner JP, Burriss MA et al. Spermine inhibits Vibrio cholerae biofilm formation through the NspS-MbaA polyamine signaling system. J Biol Chem 2017; 292:17025–17036 [View Article] [PubMed]
    [Google Scholar]
  55. Fang S-B, Huang C-J, Huang C-H, Wang K-C, Chang N-W et al. speG Is Required for Intracellular Replication of Salmonella in Various Human Cells and Affects Its Polyamine Metabolism and Global Transcriptomes. Front Microbiol 2017; 8:2245 [View Article] [PubMed]
    [Google Scholar]
  56. Okujo N, Sakakibara Y, Yoshida T, Yamamoto S. Structure of acinetoferrin, a new citrate-based dihydroxamate siderophore from Acinetobacter haemolyticus. Biometals 1994; 7:170–176 [View Article] [PubMed]
    [Google Scholar]
  57. Penwell WF, DeGrace N, Tentarelli S, Gauthier L, Gilbert CM et al. Discovery and characterization of new hydroxamate siderophores, baumannoferrin A and B, produced by Acinetobacter baumannii. Chembiochem 2015; 16:1896–1904 [View Article] [PubMed]
    [Google Scholar]
  58. Sheldon JR, Skaar EP. Acinetobacter baumannii can use multiple siderophores for iron acquisition, but only acinetobactin is required for virulence. PLOS Pathog 2020; 16:e1008995 [View Article]
    [Google Scholar]
  59. Runci F, Gentile V, Frangipani E, Rampioni G, Leoni L et al. Contribution of active iron uptake to Acinetobacter baumannii pathogenicity. Infect Immun 2019; 87:e00755-18 [View Article] [PubMed]
    [Google Scholar]
  60. Zhang M, Borovikova LV, Wang H, Metz C, Tracey KJ. Spermine inhibition of monocyte activation and inflammation. Mol Med 1999; 5:595–605 [PubMed]
    [Google Scholar]
  61. Lasbury ME, Merali S, Durant PJ, Tschang D, Ray CA et al. Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia. J Biol Chem 2007; 282:11009–11020 [View Article] [PubMed]
    [Google Scholar]
  62. Mariggiò MA, Vinella A, Pasquetto N, Curci E, Cassano A et al. In vitro effects of polyamines on polymorphonuclear cell apoptosis and implications in the pathogenesis of periodontal disease. Immunopharmacol Immunotoxicol 2004; 26:93–101 [View Article] [PubMed]
    [Google Scholar]
  63. Walters JD, Miller TJ, Cario AC, Beck FM, Marucha PT. Polyamines found in gingival fluid inhibit chemotaxis by human polymorphonuclear leukocytes in vitro. J Periodontol 1995; 66:274–278 [View Article] [PubMed]
    [Google Scholar]
  64. Mea HJ, Yong PVC, Wong EH. An overview of Acinetobacter baumannii pathogenesis: motility, adherence and biofilm formation. Microbiol Res 2021; 247:126722 [View Article] [PubMed]
    [Google Scholar]
  65. De Silva PM, Kumar A. Signal transduction proteins in Acinetobacter baumannii: role in antibiotic resistance, virulence, and potential as drug targets. Front Microbiol 2019; 10:49 [View Article] [PubMed]
    [Google Scholar]
  66. Srinivasan VB, Venkataramaiah M, Mondal A, Vaidyanathan V, Govil T et al. Functional characterization of a novel outer membrane porin KpnO, regulated by phobr two-component system in Klebsiella pneumoniae NTUH-K2044. PLOS ONE 2012; 7:e41505 [View Article]
    [Google Scholar]
  67. Nishino K, Honda T, Yamaguchi A. Genome-wide analyses of Escherichia coli gene expression responsive to the BaeSR two-component regulatory system. J Bacteriol 2005; 187:1763–1772 [View Article] [PubMed]
    [Google Scholar]
  68. Liu X, Chang Y, Xu Q, Zhang W, Huang Z et al. Mutation in the two-component regulator BaeSR mediates cefiderocol resistance and enhances virulence in Acinetobacter baumannii. mSystems 2023; 8:e01291–22 [View Article]
    [Google Scholar]
  69. Gristwood T, Fineran PC, Everson L, Williamson NR, Salmond GP. The PhoBR two-component system regulates antibiotic biosynthesis in Serratia in response to phosphate. BMC Microbiol 2009; 9:112 [View Article] [PubMed]
    [Google Scholar]
  70. Lonergan ZR, Palmer LD, Skaar EP. Histidine utilization is a critical determinant of Acinetobacter Pathogenesis. Infect Immun 2020; 88:e00118-20 [View Article] [PubMed]
    [Google Scholar]
  71. De Silva PM, Patidar R, Graham CI, Brassinga AKC, kumar A. A response regulator protein with antar domain, AvnR, in Acinetobacter baumannii ATCC 17978 impacts its virulence and amino acid metabolism. Microbiology 2020; 166:554–566 [View Article]
    [Google Scholar]
  72. Ren X, Palmer LD. Acinetobacter Metabolism in infection and antimicrobial resistance. Infect Immun 2023; 91:e0043322 [View Article] [PubMed]
    [Google Scholar]
  73. Silver RJ, Paczosa MK, McCabe AL, Balada-Llasat JM, Baleja JD et al. Amino acid biosynthetic pathways are required for Klebsiella pneumoniae growth in immunocompromised lungs and are druggable targets during infection. Antimicrob Agents Chemother 2019; 63:e02674-18 [View Article] [PubMed]
    [Google Scholar]
  74. Bachman MA, Breen P, Deornellas V, Mu Q, Zhao L et al. Genome-wide identification of Klebsiella pneumoniae fitness genes during lung infection. mBio 2015; 6:e00775 [View Article] [PubMed]
    [Google Scholar]
  75. Carfrae LA, Brown ED. Nutrient stress is a target for new antibiotics. Trends Microbiol 2023; 31:571–585 [View Article] [PubMed]
    [Google Scholar]
  76. Nairn BL, Lonergan ZR, Wang J, Braymer JJ, Zhang Y et al. The response of Acinetobacter baumannii to zinc starvation. Cell Host & Microbe 2016; 19:826–836 [View Article]
    [Google Scholar]
  77. Dib K, El Banna A, Radulescu C, Lopez Campos G, Sheehan G et al. Histamine produced by gram-negative bacteria impairs neutrophil’s antimicrobial response by engaging the histamine 2 receptor. J Innate Immun 2023; 15:153–173 [View Article] [PubMed]
    [Google Scholar]
  78. Hood MI, Skaar EP. Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol 2012; 10:525–537 [View Article] [PubMed]
    [Google Scholar]
  79. Hesse LE, Lonergan ZR, Beavers WN, Skaar EP. The Acinetobacter baumannii znu system overcomes host-imposed nutrient zinc limitation. Infect Immun 2019; 87:e00746-19 [View Article] [PubMed]
    [Google Scholar]
  80. Green ER, Juttukonda LJ, Skaar EP. The manganese-responsive transcriptional regulator MumR protects Acinetobacter baumannii from oxidative stress. Infect Immun 2020; 88:e00762-19 [View Article] [PubMed]
    [Google Scholar]
  81. Juttukonda LJ, Chazin WJ, Skaar EP. Acinetobacter baumannii coordinates urea metabolism with metal import to resist host-mediated metal limitation. mBio 2016; 7:e01475-16 [View Article] [PubMed]
    [Google Scholar]
  82. Ma Y, Fei Y, Ding S, Jiang H, Fang J et al. Trace metal elements: a bridge between host and intestinal microorganisms. Sci China Life Sci 2023; 66:1976–1993 [View Article] [PubMed]
    [Google Scholar]
  83. Qamsari MM, Rasooli I, Chaudhuri S, Astaneh SDA, Schryvers AB. Hybrid antigens expressing surface loops of ZnuD From Acinetobacter baumannii is capable of inducing protection against infection. Front Immunol 2020; 11:158 [View Article] [PubMed]
    [Google Scholar]
  84. Lee EK, Choi CH, Oh MH. Zur-regulated lipoprotein A contributes to the fitness of Acinetobacter baumannii. J Microbiol 2020; 58:67–77 [View Article] [PubMed]
    [Google Scholar]
  85. de Léséleuc L, Harris G, KuoLee R, Xu HH, Chen W. Serum resistance, gallium nitrate tolerance and extrapulmonary dissemination are linked to heme consumption in a bacteremic strain of Acinetobacter baumannii. Int J Med Microbiol 2014; 304:360–369 [View Article] [PubMed]
    [Google Scholar]
  86. Rivera M. Mobilization of iron stored in bacterioferritin, a new target for perturbing iron homeostasis and developing antibacterial and antibiofilm molecules. J Inorg Biochem 2023; 247:112306 [View Article] [PubMed]
    [Google Scholar]
  87. Gautam LK, Sharma P, Capalash N. Attenuation of Acinetobacter baumannii virulence by inhibition of polyphosphate kinase 1 with repurposed drugs. Microbiol Res 2021; 242:126627 [View Article] [PubMed]
    [Google Scholar]
  88. Gallarato LA, Sánchez DG, Olvera L, Primo ED, Garrido MN et al. Exopolyphosphatase of Pseudomonas aeruginosa is essential for the production of virulence factors, and its expression is controlled by NtrC and PhoB acting at two interspaced promoters. Microbiology (Reading) 2014; 160:406–417 [View Article] [PubMed]
    [Google Scholar]
  89. Geisinger E, Mortman NJ, Vargas-Cuebas G, Tai AK, Isberg RR. A global regulatory system links virulence and antibiotic resistance to envelope homeostasis in Acinetobacter baumannii. PLOS Pathog 2018; 14:e1007030 [View Article] [PubMed]
    [Google Scholar]
  90. Umland TC, Schultz LW, MacDonald U, Beanan JM, Olson R et al. In Vivo -validated essential genes identified in Acinetobacter baumannii by using human ascites overlap poorly with essential genes detected on laboratory media. mBio 2012; 3: [View Article]
    [Google Scholar]
  91. Matern Y, Barion B, Behrens-Kneip S. PpiD is a player in the network of periplasmic chaperones in Escherichia coli. BMC Microbiol 2010; 10:251 [View Article] [PubMed]
    [Google Scholar]
  92. Birkle K, Renschler F, Angelov A, Wilharm G, Franz-Wachtel M et al. An unprecedented tolerance to deletion of the periplasmic chaperones SurA, Skp, and DegP in the nosocomial pathogen Acinetobacter baumannii. J Bacteriol 2022; 204:e0005422 [View Article] [PubMed]
    [Google Scholar]
  93. Skurnik D, Roux D, Aschard H, Cattoir V, Yoder-Himes D et al. A comprehensive analysis of in vitro and in vivo genetic fitness of Pseudomonas aeruginosa using high-throughput sequencing of transposon libraries. PLOS Pathog 2013; 9:e1003582 [View Article] [PubMed]
    [Google Scholar]
  94. Roy R, You RI, Lin MD, Lin NT. Mutation of the carboxy-terminal processing protease in Acinetobacter baumannii affects motility, leads to loss of membrane integrity, and reduces virulence. Pathogens 2020; 9:322 [View Article] [PubMed]
    [Google Scholar]
  95. Cayô R, Rodríguez M-C, Espinal P, Fernández-Cuenca F, Ocampo-Sosa AA et al. Analysis of genes encoding penicillin-binding proteins in clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 2011; 55:5907–5913 [View Article]
    [Google Scholar]
  96. Bryan EJ, Sagong HY, Parhi AK, Grier MC, Roberge JY et al. TXH11106: a third-generation mreb inhibitor with enhanced activity against a broad range of gram-negative bacterial pathogens. Antibiotics 2022; 11:693 [View Article] [PubMed]
    [Google Scholar]
  97. Shi H, Colavin A, Bigos M, Tropini C, Monds RD et al. Deep phenotypic mapping of bacterial cytoskeletal mutants reveals physiological robustness to cell size. Current Biology 2017; 27:3419–3429 [View Article]
    [Google Scholar]
  98. Yang DC, Blair KM, Salama NR. Staying in shape: the impact of cell shape on bacterial survival in diverse environments. Microbiol Mol Biol Rev 2016; 80:187–203 [View Article]
    [Google Scholar]
  99. Lenski RE, Travisano M. Dynamics of adaptation and diversification: a 10,000-generation experiment with bacterial populations. Proc Natl Acad Sci USA 1994; 91:6808–6814 [View Article]
    [Google Scholar]
  100. Prashar A, Bhatia S, Gigliozzi D, Martin T, Duncan C et al. Filamentous morphology of bacteria delays the timing of phagosome morphogenesis in macrophages. J Cell Biol 2013; 203:1081–1097 [View Article] [PubMed]
    [Google Scholar]
  101. Xian L, Yu G, Macho AP. The GABA transaminase GabT is required for full virulence of Ralstonia solanacearum in tomato. MicroPubl Biol 2021; 2021: [View Article] [PubMed]
    [Google Scholar]
  102. Quillin SJ, Tran P, Prindle A. Potential roles for gamma-aminobutyric acid signaling in bacterial communities. Bioelectricity 2021; 3:120–125 [View Article] [PubMed]
    [Google Scholar]
  103. Jin Z, Mendu SK, Birnir B. GABA is an effective immunomodulatory molecule. Amino Acids 2013; 45:87–94 [View Article] [PubMed]
    [Google Scholar]
  104. Pearl S, Anbarasu A. Genomic landscape of nosocomial Acinetobacter baumannii: A comprehensive analysis of the resistome, virulome, and mobilome. Sci Rep 2025; 15:18203 [View Article] [PubMed]
    [Google Scholar]
  105. Mangas EL, Rubio A, Álvarez-Marín R, Labrador-Herrera G, Pachón J et al. Pangenome of Acinetobacter baumannii uncovers two groups of genomes, one of them with genes involved in CRISPR/Cas defence systems associated with the absence of plasmids and exclusive genes for biofilm formation. Microb Genom 2019; 5:e000309 [View Article] [PubMed]
    [Google Scholar]
  106. Im H, Chembilikandy V, D’Mello A, Pearson M, Tettelin H et al. Alterations in nutrient availability in the lungs during Streptococcus pneumoniae-induced pneumonia. bioRxiv 2025; 2025:2025 [View Article] [PubMed]
    [Google Scholar]
  107. Berg DE, Weiss A, Crossland L. Polarity of Tn5 insertion mutations in Escherichia coli. J Bacteriol 1980; 142:439–446 [View Article] [PubMed]
    [Google Scholar]
  108. Smith P, Schuster M. Public goods and cheating in microbes. Curr Biol 2019; 29:R442–R447 [View Article] [PubMed]
    [Google Scholar]
  109. World health organization ARDA, impact initiatives and research coordination (IRC). WHO bacterial priority pathogens list, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva 2024ISBN
    [Google Scholar]
  110. Yu Y, Ouyang Y, Yao W. shinyCircos: an R/Shiny application for interactive creation of circos plot. Bioinformatics 2018; 34:1229–1231 [View Article] [PubMed]
    [Google Scholar]
/content/journal/mgen/10.1099/mgen.0.001556
Loading
/content/journal/mgen/10.1099/mgen.0.001556
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

EXCEL
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An error occurred
Approval was partially successful, following selected items could not be processed due to error