1887

Abstract

Pulmonary infections caused by organisms of the complex are increasingly prevalent in populations at risk, such as patients with cystic fibrosis, bronchiectasis and emphysema.

infection of the lung is not observed in immunocompetent individuals, which raises the possibility that the compromised lung environment is a suitable niche for the pathogen to thrive in due to the overproduction of mucus and high amounts of host cell lysis.

Evaluate the ability of to form biofilm and grow utilizing conditions as seen in immunocompromised lungs of patients.

We compared biofilm formation and protein composition in the presence and absence of synthetic cystic fibrosis medium (SCFM) and evaluated the bacterial growth when exposed to human DNA.

is capable of forming biofilm in SCFM. By eliminating single components found in the medium, it became clear that magnesium works as a signal for the biofilm formation, and chelation of the divalent cations resulted in the suppression of biofilm formation. Investigation of the specific proteins expressed in the presence of SCFM and in the presence of SCFM lacking magnesium revealed many different proteins between the conditions. also exhibited growth in SCFM and in the presence of host cell DNA, although the mechanism of DNA utilization remains unclear.

conditions mimicking the airways of patients with cystic fibrosis appear to facilitate establishment of infection, and elimination of magnesium from the environment may affect the ability of the pathogen to establish infection.

Funding
This study was supported by the:
  • Microbiology Foundation of SF
    • Principle Award Recipient: LuizE. Bermudez
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/content/journal/jmm/10.1099/jmm.0.001467
2022-01-11
2024-04-19
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References

  1. Daley CL, Schlossberg D. Mycobacterium avium complex disease. Microbiol Spectr 2017; 5:TNM17–0045 [View Article]
    [Google Scholar]
  2. Esther CR Jr, Esserman DA, Gilligan P, Kerr A, Noone PG. Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis. J Cyst Fibros 2010; 9:117–123 [View Article] [PubMed]
    [Google Scholar]
  3. Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; 175:367–416 [View Article] [PubMed]
    [Google Scholar]
  4. Billinger ME, Olivier KN, Viboud C, de Orca BM, Steiner C et al. Nontuberculous mycobacteria associated lung disease. Emerg Infect Dis 2009; 15:1562
    [Google Scholar]
  5. Byrd TF, Lyons CR. Preliminary characterization of a Mycobacterium abscessus mutant in human and murine models of infection. Infect Immun 1999; 67:4700–4707 [View Article] [PubMed]
    [Google Scholar]
  6. Gutiérrez AV, Viljoen A, Ghigo E, Herrmann J-L, Kremer L. Glycopeptidolipids, a double-edged sword of the Mycobacterium abscessus complex. Front Microbiol 2018; 9: [View Article]
    [Google Scholar]
  7. Davidson RM. A closer look at the genomic variation of geographically diverse Mycobacterium abscessus clones that cause human infection and disease. Front Microbiol 2018; 9:1 [View Article]
    [Google Scholar]
  8. Fennelly KP, Ojano-Dirain C, Yang Q, Liu L, Lu L et al. Biofilm formation by Mycobacterium abscessus in a lung cavity. Am J Respir Crit Care Med 2016; 193:692–693 [View Article] [PubMed]
    [Google Scholar]
  9. Bernut A, Nguyen-Chi M, Halloum I, Herrmann J-L, Lutfalla G et al. Mycobacterium abscessus-induced granuloma formation is strictly dependent on TNF signaling and neutrophil trafficking. PLoS Pathog 2016; 12:e1005986 [View Article]
    [Google Scholar]
  10. Alexis NE, Muhlebach MS, Peden DB, Noah TL. Attenuation of host defense function of lung phagocytes in young cystic fibrosis patients. J Cyst Fibros 2006; 5:17–25 [View Article] [PubMed]
    [Google Scholar]
  11. Malcolm KC, Caceres SM, Pohl K, Poch KR, Bernut A et al. Neutrophil killing of Mycobacterium abscessus by intra- and extracellular mechanisms. PLoS ONE 2018; 13:e0196120 [View Article]
    [Google Scholar]
  12. Stevens DA, Moss RB, Hernandez C, Clemons KV, Martinez M. Effect of media modified to mimic cystic fibrosis sputum on the susceptibility of Aspergillus fumigatus, and the frequency of resistance at one center. Antimicrob Agents Chemother 2016; 60:2180–2184 [View Article] [PubMed]
    [Google Scholar]
  13. Schick A, Kassen R. Rapid diversification of Pseudomonas aeruginosa in cystic fibrosis lung-like conditions. Proc Natl Acad Sci U S A 2018; 115:10714–10719 [View Article] [PubMed]
    [Google Scholar]
  14. Daniel-Wayman S, Abate G, Barber DL, Bermudez LE, Coler RN et al. Advancing translational science for pulmonary nontuberculous mycobacterial infections. A road map for research. Am J Respir Crit Care Med 2019; 199:947–951 [View Article] [PubMed]
    [Google Scholar]
  15. Cherny KE, Sauer K. Pseudomonas aeruginosa requires the DNA-specific endonuclease EndA to degrade extracellular genomic DNA to disperse from the biofilm. J Bacteriol 2019; 201:e00059-19. [View Article] [PubMed]
    [Google Scholar]
  16. Rojony R, Danelishvili L, Campeau A, Wozniak JM, Gonzalez DJ et al. Exposure of Mycobacterium abscessus to environmental stress and clinically used antibiotics reveals common proteome response among pathogenic mycobacteria. Microorganisms 2020; 8:698 [View Article]
    [Google Scholar]
  17. Palmer KL, Mashburn LM, Singh PK, Whiteley M. Cystic fibrosis sputum supports growth and cues key aspects of Pseudomonas aeruginosa physiology. J Bacteriol 2005; 187:5267–5277 [View Article] [PubMed]
    [Google Scholar]
  18. O’Toole GA. To build a biofilm. J Bacteriol 2003; 185:2687–2689 [View Article]
    [Google Scholar]
  19. Babrak L, Danelishvili L, Rose S, Bermudez LE. MIP-1 is a bacterial protein associated with microaggregate formation and involved in the invasion of epithelial cells by Mycobacterium avium subsp hominissuis through the reorganization of cytoskeletal proteins. Virulence 2015; 6:649
    [Google Scholar]
  20. Blanchard JD, Elias V, Cipolla D, Gonda I, Bermudez LE. Effective treatment of Mycobacterium avium subsp. hominissuis and Mycobacterium abscessus species infections in macrophages, biofilm, and mice by using liposomal ciprofloxacin. Antimicrob Agents Chemother 2018; 62:e00440e00440-18. [View Article] [PubMed]
    [Google Scholar]
  21. Qvist T, Eickhardt S, Kragh KN, Anderson CB, Iversen M et al. Mycobacterium abscessus complex can establish a biofilm infection in the lung, which has implications for treatment. European Resp J 2015; 46:1823
    [Google Scholar]
  22. Rose S, Bermudez LE. Identification of bicarbonate as the trigger and genes involved in the export of eDNA by pathogenic Mycobacterium avium. mBio 2016; 7:e01597
    [Google Scholar]
  23. Obregón-Henao A, Arnett KA, Henao-Tamayo M, Massoudi L, Creissen E et al. Susceptibility of Mycobacterium abscessus to antimycobacterial drugs in preclinical models. Antimicrob Agents Chemother 2015; 59:6904–6912 [View Article] [PubMed]
    [Google Scholar]
  24. Saunders SH, Tse ECM, Yates MD, Otero FJ, Trammell SA et al. Extracellular DNA promotes efficient extracellular electron transfer by pyocyanin in Pseudomonas aeruginosa biofilms. Cell 2020; 182:919–932919 [View Article]
    [Google Scholar]
  25. Rose SJ, Babrak LM, Bermudez LE. Mycobacterium avium possesses extracellular DNA that contributes to biofilm formation, structural integrity, and tolerance to antibiotics. PLoS One 2015; 10:e0128772. [View Article] [PubMed]
    [Google Scholar]
  26. Rose SJ, Bermudez LE. Mycobacterium avium biofilm attenuates mononuclear phagocyte function by triggering hyperstimulation and apoptosis during early infection. Infect Immun 2014; 82:405–412 [View Article] [PubMed]
    [Google Scholar]
  27. Kumar B, Cardona ST. Synthetic cystic fibrosis sputum medium regulates flagellar biosynthesis through the flhF gene in Burkholderia cenocepacia. Front Cell Infect Microbiol 2016; 6:65. [View Article] [PubMed]
    [Google Scholar]
  28. Bechler J, Bermudez LE. Investigating the role of mucin as frontline defense of mucosal surfaces against Mycobacterium avium subsp. hominissuis. Journal of Pathogens 2020; 2020:1–7 [View Article]
    [Google Scholar]
  29. Bryant JM, Grogono DM, Greaves D, Foweraker J, Roddick I et al. Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study. Lancet 2013; 381:1551–1560 [View Article] [PubMed]
    [Google Scholar]
  30. Pelcekova Z, Gilleron M, Angala SK, Belardinelli JM, McNeil M et al. Tailoring modification of cell envelope polysaccharides impacts the intracellular survival of Mycobacterium abscessus. ACS Infect Dis 2020; 6:2235
    [Google Scholar]
  31. Bruscia EM, Bonfield TL. Cystic fibrosis lung immunity: the role of the macrophage. J Innate Immun 2016; 8:550–563 [View Article] [PubMed]
    [Google Scholar]
  32. Silo-Suh L, Suh SJ, Phibbs PV, Ohman DE. Adaptations of Pseudomonas aeruginosa to the cystic fibrosis lung environment can include deregulation of zwf, encoding glucose-6-phosphate dehydrogenase. J Bacteriol 2005; 187:7561–7568 [View Article]
    [Google Scholar]
  33. Miller SI, Mekalanos JJ. Constitutive expression of the phoP regulon attenuates Salmonella virulence and survival within macrophages. J Bacteriol 1990; 172:2485–2490 [View Article]
    [Google Scholar]
  34. Gonzalo-Asensio J, Soto CY, Arbués A, Sancho J, del Carmen Menéndez M et al. The Mycobacterium tuberculosis phoPR operon is positively autoregulated in the virulent strain H37Rv. J Bacteriol 2008; 190:7068–7078 [View Article] [PubMed]
    [Google Scholar]
  35. Davies DG, Geesey GG. Regulation of the alginate biosynthesis gene algC in Pseudomonas aeruginosa during biofilm development in continuous culture. Appl Environ Microbiol 1995; 61:860–867 [View Article] [PubMed]
    [Google Scholar]
  36. Banin E, Brady KM, Greenberg EP. Chelator-induced dispersal and killing of Pseudomonas aeruginosa cells in a biofilm. Appl Environ Microbiol 2006; 72:2064–2069 [View Article] [PubMed]
    [Google Scholar]
  37. Wang T, Flint S, Palmer J. Magnesium and calcium ions: roles in bacterial cell attachment and biofilm structure maturation. Biofouling 2019; 35:959–974959 [View Article] [PubMed]
    [Google Scholar]
  38. Dempwolff F, Möller HM, Graumann PL. Synthetic motility and cell shape defects associated with deletions of flotillin/reggie paralogs in Bacillus subtilis and interplay of these proteins with NfeD proteins. J Bacteriol 2012; 194:4652–4661 [View Article] [PubMed]
    [Google Scholar]
  39. Bear CE. A therapy for most with cystic fibrosis. Cell 2020; 180: [View Article] [PubMed]
    [Google Scholar]
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