Lactobacillus crispatus ức chế sự phát triển của Gardnerella vaginalis và Neisseria gonorrhoeae trên mô hình niêm mạc âm đạo heo

BMC Microbiology - Tập 15 - Trang 1-12 - 2015
Laura M. Breshears1, Vonetta L. Edwards2, Jacques Ravel2, Marnie L. Peterson1
1Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, USA
2Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, USA

Tóm tắt

Hệ vi sinh âm đạo có thể ảnh hưởng đến mức độ nhạy cảm của phụ nữ đối với viêm âm đạo do vi khuẩn (BV) và các bệnh lây truyền qua đường tình dục (STI). BV được đặc trưng bởi sự giảm bớt Lactobacillus spp., sự phát triển quá mức của vi khuẩn kỵ khí (thường do Gardnerella vaginalis chiếm ưu thế) và pH > 4.5. BV liên quan đến nguy cơ tăng cao khi mắc các STI như chlamydia và đau mắt hột. Mặc dù đã xác định được các mối liên hệ này, nhưng các cơ chế phân tử điều khiển nguy cơ nhiễm trùng vẫn chưa được biết đến. Một mô hình niêm mạc âm đạo heo ex vivo (PVM) đã được phát triển để khám phá vai trò cơ chế của Lactobacillus spp. trong việc ảnh hưởng đến sự thuộc địa của G. vaginalis và Neisseria gonorrhoeae. Dữ liệu được trình bày ở đây cho thấy tất cả các sinh vật được thử nghiệm đều có thể thuộc địa hóa và phát triển trên PVM ở mức độ mật độ lâm sàng có liên quan. Thêm vào đó, G. vaginalis và N. gonorrhoeae hình thành màng sinh học trên PVM. Đã quan sát thấy rằng axit lactic, axit acetic và axit hydrochloric ức chế sự phát triển của G. vaginalis trên PVM theo cách phụ thuộc vào pH. N. gonorrhoeae phát triển tốt nhất trong sự hiện diện của axit lactic ở pH 5.5, nhưng không phát triển tốt ở pH này khi có axit acetic. Cuối cùng, một chủng Lactobacillus crispatus lâm sàng (24-9-7) sản xuất axit lactic và ức chế sự phát triển của cả G. vaginalis và N. gonorrhoeae trên PVM. Dữ liệu này tiết lộ sự khác biệt trong ảnh hưởng của pH, các axit khác nhau và L. crispatus đối với sự phát triển của G. vaginalis và N. gonorrhoeae trên bề mặt niêm mạc âm đạo sống. PVM là một mô hình hữu ích để nghiên cứu sự tương tác giữa vi khuẩn âm đạo cộng sinh với các mầm bệnh và các cơ chế hình thành màng sinh học trên niêm mạc âm đạo.

Từ khóa

#Lactobacillus crispatus #Gardnerella vaginalis #Neisseria gonorrhoeae #mô hình niêm mạc âm đạo heo #viêm âm đạo do vi khuẩn #bệnh lây truyền qua đường tình dục

Tài liệu tham khảo

Barrett S, Taylor C. A review on pelvic inflammatory disease. Int J STD AIDS. 2005;16:715–20. Schwebke JR. Bacterial vaginosis: are we coming full circle? J Infect Dis. 2009;200:1633–5. Swidsinski A, Doerffel Y, Loening-Baucke V, Swidsinski S, Verstraelen H, Vaneechoutte M, et al. Gardnerella biofilm involves females and males and is transmitted sexually. Gynecol Obstet Inves. 2010;70:256–63. Hillier SL, Krohn MA, Cassen E, Easterling TR, Rabe LK, Eschenbach DA. The role of bacterial vaginosis and vaginal bacteria in amniotic fluid infection in women in preterm labor with intact fetal membranes. Clin Infect Dis. 1995;20 Suppl 2:S276–8. Hitti J, Hillier SL, Agnew KJ, Krohn MA, Reisner DP, Eschenbach DA. Vaginal indicators of amniotic fluid infection in preterm labor. Obstet Gynecol. 2001;97:211–9. Sewankambo N, Gray RH, Wawer MJ, Paxton L, McNairn D, Wabwire-Mangen F, et al. HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis. Lancet. 1997;350:546–50. Watts DH, Krohn MA, Hillier SL, Eschenbach DA. Bacterial vaginosis as a risk factor for post-cesarean endometritis. Obstet Gynecol. 1990;75:52–8. Wiesenfeld HC, Hillier SL, Krohn MA, Amortegui AJ, Heine RP, Landers DV, et al. Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Obstet Gynecol. 2002;100:456–63. Wiesenfeld HC, Hillier SL, Krohn MA, Landers DV, Sweet RL. Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis. 2003;36:663–8. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular Identification of Bacteria Associated with Bacterial Vaginosis. N Engl J Med. 2005;353:1899–911. Hill GB. The microbiology of bacterial vaginosis. Am J Obstet Gynecol. 1993;169:450–4. Spiegel CA. Bacterial vaginosis. Clin Microbiol Rev. 1991;4:485–502. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol. 1991;29:297–301. Kenyon CR, Osbak K. Recent progress in understanding the epidemiology of bacterial vaginosis. Curr Opin Obstet Gyn. 2014;26:448–54. Turovskiy Y, Sutyak Noll K, Chikindas ML. The aetiology of bacterial vaginosis. J Appl Microbiol. 2011;110:1105–28. Antonio MA, Hawes SE, Hillier SL. The identification of vaginal Lactobacillus species and the demographic and microbiologic characteristics of women colonized by these species. J Infect Dis. 1999;180:1950–6. Hillier SL, Krohn MA, Klebanoff SJ, Eschenbach DA. The relationship of hydrogen peroxide-producing lactobacilli to bacterial vaginosis and genital microflora in pregnant women. Obstet Gynecol. 1992;79:369–73. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SSK, McCulle SL, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4680–7. Sobel JD. Is there a protective role for vaginal flora? Curr Infect Dis Rep. 1999;1:379–83. Saigh JH, Sanders C, Sanders WEJ. Inhibition of Neisseria gonorrhoeae by aerobic and facultatively anaerobic components of the endocervical flora: evidence for a protective effect against infection. Infect Immun. 1978;19:704–10. Aroutcheva A, Gariti D, Simon M, Shott S, Faro J, Simoes JA, et al. Defense factors of vaginal Lactobacilli. Am J Obstet Gynecol. 2001;185:375–9. Atassi F, Brassart D, Grob P, Graf F, Servin AL. Lactobacillus strains isolated from the vaginal microbiota of healthy women inhibit Prevotella bivia and Gardnerella vaginalis in coculture and cell culture. FEMS Immunol Med Mic. 2006;48:424–32. Dover SE, Aroutcheva AA, Faro S, Chikindas ML. Natural antimicrobials and their role in vaginal health: a short review. Int J Probiotics Prebiotics. 2008;3:219–30. Eschenbach DA, Davick PR, Williams BL, Klebanoff SJ, Young-Smith K, Critchlow CM, et al. Prevalence of hydrogen peroxide-producing Lactobacillus species in normal women and women with bacterial vaginosis. J Clin Microbiol. 1989;27:251–6. Graver MA, Wade JJ. The role of acidification in the inhibition of Neisseria gonorrhoeae by vaginal lactobacilli during anaerobic growth. Ann Clin Microbiol Antimicrob. 2011;10:8. O’Hanlon DE, Moench TR, Cone RA. In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Infect Dis. 2011;11:200. St Amant DC, Valentin-Bon IE, Jerse AE. Inhibition of Neisseria gonorrhoeae by Lactobacillus species that are commonly isolated from the female genital tract. Infect Immun. 2002;70:7169–71. Zheng HY, Alcorn TM, Cohen MS. Effects of H2O2-producing lactobacilli on Neisseria gonorrhoeae growth and catalase activity. J Infect Dis. 1994;170:1209–15. Barfod KK, Roggenbuck M, Hansen LH, Schjørring S, Larsen ST, Sørensen SJ, et al. The murine lung microbiome in relation to the intestinal and vaginal bacterial communities. BMC Microbiol. 2013;13:303. Gilbert NM, Lewis WG, Lewis AL. Clinical features of bacterial vaginosis in a murine model of vaginal infection with Gardnerella vaginalis. PLoS One. 2013;8:e59539. Hymes SR, Randis TM, Sun TY, Ratner AJ. DNase inhibits Gardnerella vaginalis biofilms in vitro and in vivo. J Infect Dis. 2013;207:1491–7. Jerse AE, Wu H, Packiam M, Vonck RA, Begum AA, Garvin LE. Estradiol-treated female mice as surrogate hosts for Neisseria gonorrhoeae genital tract infections. Front Microb. 2011;2:107. Spencer SE, Valentin-Bon IE, Whaley K, Jerse AE. Inhibition of Neisseria gonorrhoeae genital tract infection by leading-candidate topical microbicides in a mouse model. J Infect Dis. 2004;189:410–9. Squier CA, Mantz MJ, Schlievert PM, Davis CC. Porcine vagina ex vivo as a model for studying permeability and pathogenesis in mucosa. J Pharm Sci. 2008;97:9–21. Anderson MJ, Horn ME, Lin Y-C, Parks PJ, Peterson ML. Efficacy of concurrent application of chlorhexidine gluconate and povidone iodine against six nosocomial pathogens. Am J Infect Control. 2010;38:826–31. Anderson MJ, Lin Y-C, Gillman AN, Parks PJ, Schlievert PM, Peterson ML. Alpha-toxin promotes Staphylococcus aureus mucosal biofilm formation. Front Cell Infect Microb. 2012;2:64. Anderson MJ, Parks PJ, Peterson ML. A mucosal model to study microbial biofilm development and anti-biofilm therapeutics. J Microbiol Meth. 2013;92:201–8. Anderson MJ, Scholz MT, Parks PJ, Peterson ML. Ex vivo porcine vaginal mucosal model of infection for determining effectiveness and toxicity of antiseptics. J Appl Microbiol. 2013;115:679–88. Brosnahan AJ, Schaefers MM, Amundson WH, Mantz MJ, Squier CA, Peterson ML, et al. Novel toxic shock syndrome toxin-1 amino acids required for biological activity. Biochem. 2008;47:12995–3003. Brosnahan AJ, Mantz MJ, Squier CA, Peterson ML, Schlievert PM. Cytolysins augment superantigen penetration of stratified mucosa. J Immunol. 2009;182:2364–73. Davis CC, Kremer MJ, Schlievert PM, Squier CA. Penetration of toxic shock syndrome toxin-1 across porcine vaginal mucosa ex vivo: permeability characteristics, toxin distribution, and tissue damage. Am J Obstet Gynecol. 2003;189:1785–91. Davis CC, Baccam M, Mantz MJ, Osborn TW, Hill DR, Squier CA. Use of porcine vaginal tissue ex-vivo to model environmental effects on vaginal mucosa to toxic shock syndrome toxin-1. Toxicol Appl Pharm. 2014;274:240–8. Lin Y-C, Anderson MJ, Kohler PL, Strandberg KL, Olson ME, Horswill AR, et al. Proinflammatory exoprotein characterization of toxic shock syndrome Staphylococcus aureus. Biochem. 2011;50:7157–67. Peterson ML, Ault K, Kremer MJ, Klingelhutz AJ, Davis CC, Squier CA, et al. The innate immune system is activated by stimulation of vaginal epithelial cells with Staphylococcus aureus and toxic shock syndrome toxin 1. Infect Immun. 2005;73:2164–74. Schaefers MM, Breshears LM, Anderson MJ, Lin Y-C, Grill AE, Panyam J, et al. Epithelial proinflammatory response and curcumin-mediated protection from staphylococcal toxic shock syndrome toxin-1. PLoS One. 2012;7:e32813. Yang Q, Phillips PL, Sampson EM, Progulske-Fox A, Jin S, Antonelli P, et al. Development of a novel ex vivo porcine skin explant model for the assessment of mature bacterial biofilms. Wound Repair Regen. 2013;21:704–14. Greiner LL, Edwards JL, Shao J, Rabinak C, Entz D, Apicella MA. Biofilm formation by Neisseria gonorrhoeae. Infect Immun. 2005;73:1964–70. Steichen CT, Shao JQ, Ketterer MR, Apicella MA. Gonococcal cervicitis: a role for biofilm in pathogenesis. J Infect Dis. 2008;198:1856–61. Muli FW, Struthers JK. The growth of Gardnerella vaginalis and Lactobacillus acidophilus in Sorbarod biofilms. J Med Microbiol. 1998;47:401–5. Swidsinski A, Mendling W, Loening-Baucke V, Ladhoff A, Swidsinski S, Hale LP, et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol. 2005;106:1013–23. Swidsinski A, Mendling W, Loening-Baucke V, Swidsinski S, Dörffel Y, Scholze J, et al. An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole. Am J Obstet Gynecol. 2008;198:97.e1-97.e6. Swidsinski A, Dörffel Y, Loening-Baucke V, Schilling J, Mendling W. Response of Gardnerella vaginalis biofilm to 5 days of moxifloxacin treatment. FEMS Immunol Med Mic. 2010;61:41–6. Al-Mushrif S, Eley A, Jones BM. Inhibition of chemotaxis by organic acids from anaerobes may prevent a purulent response in bacterial vaginosis. J Med Microbiol. 2000;49:1023–30. Chaudry AN, Travers PJ, Yuenger J, Colletta L, Evans P, Zenilman JM, et al. Analysis of vaginal acetic acid in patients undergoing treatment for bacterial vaginosis. J Clin Microbiol. 2004;42:5170–5. Mirmonsef P, Gilbert D, Zariffard MR, Hamaker BR, Kaur A, Landay AL, et al. The Effects of Commensal Bacteria on Innate Immune Responses in the Female Genital Tract. Am J Reprod Immunol. 2010;65:190–5. Stanek R, Gain RE, Glover DD, Larsen B. High performance ion exclusion chromatographic characterization of the vaginal organic acids in women with bacterial vaginosis. Biomed Chromatogr. 1992;6:231–5. Klebanoff SJ, Hillier SL, Eschenbach DA, Waltersdorph AM. Control of the microbial flora of the vagina by H2O2-generating lactobacilli. J Infect Dis. 1991;164:94–100. Edwards JL, Shao JQ, Ault KA, Apicella MA. Neisseria gonorrhoeae elicits membrane ruffling and cytoskeletal rearrangements upon infection of primary human endocervical and ectocervical cells. Infect Immun. 2000;68:5354–63. Edwards JL, Brown EJ, Ault KA, Apicella MA. The role of complement receptor 3 (CR3) in Neisseria gonorrhoeae infection of human cervical epithelia. Cell Microbiol. 2001;3:611–22. Edwards JL, Butler EK. The pathobiology of Neisseria gonorrhoeae lower female genital tract infection. Front Microb. 2011;2:102. Evans BA. Ultrastructural study of cervical gonorrhea. J Infect Dis. 1977;136:248–55. Aleshkin VA, Voropaeva EA, Shenderov BA. Vaginal microbiota in healthy women and patients with bacterial vaginosis and nonspecific vaginitis. Microb Ecol Health D. 2006;18:71–4. Antonio MAD, Meyn LA, Murray PJ, Busse B, Hillier SL. Vaginal colonization by probiotic Lactobacillus crispatus CTV-05 is decreased by sexual activity and endogenous Lactobacilli. J Infect Dis. 2009;199:1506–13. Sheiness D, Dix K, Watanabe S, Hillier SL. High levels of Gardnerella vaginalis detected with an oligonucleotide probe combined with elevated pH as a diagnostic indicator of bacterial vaginosis. J Clin Microbiol. 1992;30:642–8. Young H, Sarafian SK, Harris AB, McMillan A. Non-cultural detection of Neisseria gonorrhoeae in cervical and vaginal washings. J Med Microbiol. 1983;16:183–91. Alves P, Castro J, Sousa C, Cereija TB, Cerca N. Gardnerella vaginalis outcompetes 29 other bacterial species isolated from patients with bacterial vaginosis, using in an in vitro biofilm formation model. J Infect Dis. 2014;210:593–6. Patterson JL, Stull-Lane A, Girerd PH, Jefferson KK. Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes. Microbiology. 2010;156:392–9. Harwich MD, Alves JM, Buck GA, Strauss JF, Patterson JL, Oki AT, et al. Drawing the line between commensal and pathogenic Gardnerella vaginalis through genome analysis and virulence studies. BMC Genomics. 2010;11:375. Gelber SE, Aguilar JL, Lewis KLT, Ratner AJ. Functional and phylogenetic characterization of Vaginolysin, the human-specific cytolysin from Gardnerella vaginalis. J Bacteriol. 2008;190:3896–903. Rottini G, Dobrina A, Forgiarini O, Nardon E, Amirante GA, Patriarca P. Identification and partial characterization of a cytolytic toxin produced by Gardnerella vaginalis. Infect Immun. 1990;58:3751–8. Hooven TA, Randis TM, Hymes SR, Rampersaud R, Ratner AJ. Retrocyclin inhibits Gardnerella vaginalis biofilm formation and toxin activity. J Antimicrob Chemother. 2012;67:2870–2. Blanchette-Cain K, Hinojosa CA, Akula Suresh Babu R, Lizcano A, Gonzalez-Juarbe N, Munoz-Almagro C, et al. Streptococcus pneumoniae Biofilm Formation Is Strain Dependent, Multifactorial, and Associated with Reduced Invasiveness and Immunoreactivity during Colonization. mBio. 2013;4:e00745-13. Ahmed A, Earl J, Retchless A, Hillier SL, Rabe LK, Cherpes TL, et al. Comparative genomic analyses of 17 clinical isolates of Gardnerella vaginalis provide evidence of multiple genetically isolated clades consistent with subspeciation into genovars. J Bacteriol. 2012;194:3922–37. Spurbeck RR, Arvidson CG. Lactobacilli at the front line of defense against vaginally acquired infections. Future Microbiol. 2011;6:567–82. Witkin SS, Mendes-Soares H, Linhares IM, Jayaram A, Ledger WJ, Forney LJ. Influence of vaginal bacteria and D- and L-lactic acid isomers on vaginal extracellular matrix metalloproteinase inducer: implications for protection against upper genital tract infections. mBio. 2013;4:e00460–13. O’Hanlon DE, Lanier BR, Moench TR, Cone RA. Cervicovaginal fluid and semen block the microbicidal activity of hydrogen peroxide produced by vaginal lactobacilli. BMC Infect Dis. 2010;10:120. Anderson MJ, David ML, Scholz M, Bull SJ, Morse D, Hulse-Stevens M, et al. Efficacy of Skin and Nasal Povidone-Iodine Preparation against Mupirocin-Resistant Methicillin-Resistant Staphylococcus aureus and S. aureus within the Anterior Nares. Antimicrob Agents Chemother. 2015;59:2765–73. Parma M, Stella Vanni V, Bertini M, Candiani M. Probiotics in the prevention of recurrences of bacterial vaginosis. Altern Ther Health M. 2014;20:52–7. Gajer P, Brotman RM, Bai G, Sakamoto J, Schutte UME, Zhong X, et al. Temporal Dynamics of the Human Vaginal Microbiota. Sci Transl Med. 2012;4:132ra52-132ra52. Ravel J, Brotman RM, Gajer P, Ma B, Nandy M, Fadrosh DW, et al. Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis. Microbiome. 2013;1:29.