Protective effects of membrane vesicles against stress and antimicrobial agents Open Access

Abstract

Outer-membrane vesicles (OMVs) produced by deliver bacterial components to host cells, provide a mechanism for stabilization of secreted components and may allow the bacteria to exert ‘long-range’ effects in the gastric niche, promoting persistence. In addition to their well-characterized host cell interactions, membrane vesicles improve stress survival in other bacterial species, and are constitutively produced by both pathogenic and non-pathogenic bacteria. We aimed to determine whether OMVs could improve survival of a range of stressors. The effects of purified OMVs on the resistance of to a range of environmental and antimicrobial stresses were determined using growth curves and survival assays. Addition of purified OMVs to cultures provided dose-dependent protection against hydrogen peroxide-mediated killing. Supplementation with OMVs also partially protected against the bactericidal effects of the antibiotics clarithromycin and levofloxacin, but not against amoxicillin nor metronidazole. Addition of purified OMVs allowed to grow in the presence of inhibitory concentrations of the antimicrobial peptide LL-37. In the presence of 50 µg OMVs ml, significantly enhanced growth was observed at higher LL-37 concentrations compared with lower LL-37 concentrations, suggesting that OMV–LL-37 interactions might facilitate release of growth-promoting nutrients. Taken together, these data indicate that production of membrane vesicles could help to survive exposure to antibiotics and host antimicrobial defences during infection.

Funding
This study was supported by the:
  • Government of the State of Kuwait
    • Principle Award Recipient: Lolwah Mohammad Alsharaf
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.000934
2020-05-28
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/micro/166/8/751.html?itemId=/content/journal/micro/10.1099/mic.0.000934&mimeType=html&fmt=ahah

References

  1. Peek RM, Fiske C, Wilson KT. Role of innate immunity in Helicobacter pylori-induced gastric malignancy. Physiol Rev 2010; 90:831–858 [View Article][PubMed]
    [Google Scholar]
  2. Atherton JC, Blaser MJ. Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J Clin Invest 2009; 119:2475–2487 [View Article][PubMed]
    [Google Scholar]
  3. Atherton JC. The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases. Annu Rev Pathol 2006; 1:63–96 [View Article][PubMed]
    [Google Scholar]
  4. Thung I, Aramin H, Vavinskaya V, Gupta S, Park JY et al. Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther 2016; 43:514–533 [View Article][PubMed]
    [Google Scholar]
  5. Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ et al. Management of Helicobacter pylori infection-the Maastricht V/Florence consensus report. Gut 2017; 66:6–30 [View Article][PubMed]
    [Google Scholar]
  6. Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization regions. Gastroenterology 2018; 155:1372–1382 [View Article][PubMed]
    [Google Scholar]
  7. Miendje Deyi VY, Lare MS, Burette A, Ntounda R, Elkilic O et al. Update of primary Helicobacter pylori resistance to antimicrobials in Brussels, Belgium. Diagn Microbiol Infect Dis 2019; 95:114875 [View Article][PubMed]
    [Google Scholar]
  8. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018; 18:318–327 [View Article][PubMed]
    [Google Scholar]
  9. Keenan J, Day T, Neal S, Cook B, Perez-Perez G et al. A role for the bacterial outer membrane in the pathogenesis of Helicobacter pylori infection. FEMS Microbiol Lett 2000; 182:259–264 [View Article][PubMed]
    [Google Scholar]
  10. Fiocca R, Necchi V, Sommi P, Ricci V, Telford J et al. Release of Helicobacter pylori vacuolating cytotoxin by both a specific secretion pathway and budding of outer membrane vesicles. Uptake of released toxin and vesicles by gastric epithelium. J Pathol 1999; 188:220–226 [View Article][PubMed]
    [Google Scholar]
  11. Schwechheimer C, Kuehn MJ. Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat Rev Microbiol 2015; 13:605–619 [View Article][PubMed]
    [Google Scholar]
  12. Mullaney E, Brown PA, Smith SM, Botting CH, Yamaoka YY et al. Proteomic and functional characterization of the outer membrane vesicles from the gastric pathogen Helicobacter pylori . Proteomics Clin Appl 2009; 3:785–796 [View Article][PubMed]
    [Google Scholar]
  13. Olofsson A, Vallström A, Petzold K, Tegtmeyer N, Schleucher J et al. Biochemical and functional characterization of Helicobacter pylori vesicles. Mol Microbiol 2010; 77:1539–1555 [View Article][PubMed]
    [Google Scholar]
  14. Olofsson A, Nygård Skalman L, Obi I, Lundmark R, Arnqvist A. Uptake of Helicobacter pylori vesicles is facilitated by clathrin-dependent and clathrin-independent endocytic pathways. mBio 2014; 5:e00979-14 [View Article][PubMed]
    [Google Scholar]
  15. Turner L, Bitto NJ, Steer DL, Lo C, D'Costa K et al. Helicobacter pylori outer membrane vesicle size determines their mechanisms of host cell entry and protein content. Front Immunol 2018; 9:1466 [View Article][PubMed]
    [Google Scholar]
  16. MacDonald IA, Kuehn MJ. Offense and defense: microbial membrane vesicles play both ways. Res Microbiol 2012; 163:607–618 [View Article][PubMed]
    [Google Scholar]
  17. MacDonald IA, Kuehn MJ. Stress-induced outer membrane vesicle production by Pseudomonas aeruginosa . J Bacteriol 2013; 195:2971–2981 [View Article][PubMed]
    [Google Scholar]
  18. Schwechheimer C, Kuehn MJ. Synthetic effect between envelope stress and lack of outer membrane vesicle production in Escherichia coli . J Bacteriol 2013; 195:4161–4173 [View Article][PubMed]
    [Google Scholar]
  19. McBroom AJ, Kuehn MJ. Release of outer membrane vesicles by Gram‐negative bacteria is a novel envelope stress response. Mol Microbiol 2007; 63:545–558 [View Article][PubMed]
    [Google Scholar]
  20. Kulkarni HM, Nagaraj R, Jagannadham MV. Protective role of E. coli outer membrane vesicles against antibiotics. Microbiol Res 2015; 181:1–7 [View Article][PubMed]
    [Google Scholar]
  21. Manning AJ, Kuehn MJ. Contribution of bacterial outer membrane vesicles to innate bacterial defense. BMC Microbiol 2011; 11:258 [View Article][PubMed]
    [Google Scholar]
  22. Kulkarni HM, Swamy CVB, Jagannadham MV. Molecular characterization and functional analysis of outer membrane vesicles from the Antarctic bacterium Pseudomonas syringae suggest a possible response to environmental conditions. J Proteome Res 2014; 13:1345–1358 [View Article][PubMed]
    [Google Scholar]
  23. Lekmeechai S, Su Y-C, Brant M, Alvarado-Kristensson M, Vallström A et al. Helicobacter pylori outer membrane vesicles protect the pathogen from reactive oxygen species of the respiratory burst. Front Microbiol 2018; 9:1837 [View Article][PubMed]
    [Google Scholar]
  24. Hase K, Murakami M, Iimura M, Cole SP, Horibe Y et al. Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori . Gastroenterology 2003; 125:1613–1625 [View Article][PubMed]
    [Google Scholar]
  25. Winter J, Letley D, Rhead J, Atherton J, Robinson K. Helicobacter pylori membrane vesicles stimulate innate pro- and anti-inflammatory responses and induce apoptosis in Jurkat T cells. Infect Immun 2014; 82:1372–1381 [View Article][PubMed]
    [Google Scholar]
  26. Duperthuy M, Sjöström AE, Sabharwal D, Damghani F, Uhlin BE et al. Role of the Vibrio cholerae matrix protein BAP1 in cross-resistance to antimicrobial peptides. PLoS Pathog 2013; 9:e1003620 [View Article][PubMed]
    [Google Scholar]
  27. Lee J, Lee E-Y, Kim S-H, Kim D-K, Park K-S et al. Staphylococcus aureus extracellular vesicles carry biologically active β-lactamase. Antimicrob Agents Chemother 2013; 57:2589–2595 [View Article][PubMed]
    [Google Scholar]
  28. Liao Y-T, Kuo S-C, Chiang M-H, Lee Y-T, Sung W-C et al. Acinetobacter baumannii extracellular OXA-58 is primarily and selectively released via outer membrane vesicles after Sec-dependent periplasmic translocation. Antimicrob Agents Chemother 2015; 59:7346–7354 [View Article][PubMed]
    [Google Scholar]
  29. Co E-MA, Schiller NL. Resistance mechanisms in an in vitro-selected amoxicillin-resistant strain of Helicobacter pylori . Antimicrob Agents Chemother 2006; 50:4174–4176 [View Article][PubMed]
    [Google Scholar]
  30. Xuan S-H, Wu L-P, Zhou Y-G, Xiao M-B. Detection of clarithromycin-resistant Helicobacter pylori in clinical specimens by molecular methods: a review. J Glob Antimicrob Resist 2016; 4:35–41 [View Article][PubMed]
    [Google Scholar]
  31. Doucet-Populaire F, Capobianco JO, Zakula D, Jarlier V, Goldman RC. Molecular basis of clarithromycin activity against Mycobacterium avium and Mycobacterium smegmatis . J Antimicrob Chemother 1998; 41:179–187 [View Article][PubMed]
    [Google Scholar]
  32. Delcour AH. Outer membrane permeability and antibiotic resistance. Biochim Biophys Acta 2009; 1794:808–816 [View Article][PubMed]
    [Google Scholar]
  33. Kosol S, Schrank E, Krajačić MB, Wagner GE, Meyer NH et al. Probing the interactions of macrolide antibiotics with membrane-mimetics by NMR spectroscopy. J Med Chem 2012; 55:5632–5636 [View Article][PubMed]
    [Google Scholar]
  34. Chen J, Ye L, Jin L, Xu X, Xu P et al. Application of next-generation sequencing to characterize novel mutations in clarithromycin-susceptible Helicobacter pylori strains with A2143G of 23S rRNA gene. Ann Clin Microbiol Antimicrob 2018; 17:10 [View Article][PubMed]
    [Google Scholar]
  35. Smiley R, Bailey J, Sethuraman M, Posecion N, Showkat Ali M. Comparative proteomics analysis of sarcosine insoluble outer membrane proteins from clarithromycin resistant and sensitive strains of Helicobacter pylori . J Microbiol 2013; 51:612–618 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.000934
Loading
/content/journal/micro/10.1099/mic.0.000934
Loading

Data & Media loading...

Most cited Most Cited RSS feed