Vaccination with a live-attenuated small-colony variant improves the humoral and cell-mediated responses against Staphylococcus aureus
Autoři:
Julie Côté-Gravel aff001; Eric Brouillette aff001; François Malouin aff001
Působiště autorů:
Centre d’étude et de Valorisation de la Diversité Microbienne (CEVDM), Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, Canada
aff001
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0227109
Souhrn
Staphylococcus aureus is known to produce persistent and chronic infections in both humans and animals. It is recognized that small-colony variants (SCVs), which produce higher levels of biofilm and that are capable of intracellular persistence, contribute to the chronicity or recurrence of infections and that this phenotype is inherent to the pathogenesis process. Prevention of S. aureus infections through vaccination has not yet met with considerable success. Some of the current vaccine formulations for S. aureus bovine mastitis consist of inactivated S. aureus bacteria, sometimes combined to E. coli J5. As such, the stimulation of cell-mediated immunity by these vaccines might not be optimal. With this in mind, we recently engineered a genetically stable double mutant SCV (ΔvraGΔhemB), which was highly attenuated in a mastitis model of infection. The present work describes the immune responses elicited in mice by various experimental vaccine compositions including the live-attenuated SCV double mutant and its inactivated form, combined or not with inactivated E. coli J5. The live-attenuated SCV was found to provoke a strong and balanced humoral response in immunized mice, as well as strong proliferation of ex-vivo stimulated splenocytes isolated from these animals. These splenocytes were also found to release high concentration of IL-17 and IFN-γ when compared to every other vaccination formulation. Inversely, the inactivated whole-cell vaccine, alone or in combination with the E. coli J5 bacterin, elicited lower antibody titers and failed to induce Th1 or Th17 cell-mediated responses in the splenocyte proliferation assay. Our results suggest that live-attenuated SCVs can trigger host immunity differently than inactivated bacteria and could represent a suitable vector for inducing strong humoral and cell-mediated immune responses, which are crucial for protection. This could represent an important improvement over existing vaccine formulations for preventing S. aureus bovine mastitis and other infections caused by this pathogen.
Klíčová slova:
Immune response – Vaccination and immunization – Staphylococcus aureus – Vaccines – Antibodies – Spleen – Bovine mastitis – Humoral immune response
Zdroje
1. Foster TJ. Immune evasion by staphylococci. Nat Rev Microbiol. 2005;3: 948–958. doi: 10.1038/nrmicro1289 16322743
2. Goldmann O, Medina E. Staphylococcus aureus strategies to evade the host acquired immune response. Int J Med Microbiol. 2018;308: 625–630. doi: 10.1016/j.ijmm.2017.09.013 28939437
3. Fowler V, Proctor R. Where does a Staphylococcus aureus vaccine stand? Clin Microbiol Infect. 2014;20 Suppl 5: 66–75. doi: 10.1111/1469-0691.12570 24476315
4. Reyher KK, Dufour S, Barkema HW, Des Côteaux L, Devries TJ, Dohoo IR, et al. The National Cohort of Dairy Farms—a data collection platform for mastitis research in Canada. J Dairy Sci. 2011;94: 1616–1626. doi: 10.3168/jds.2010-3180 21338829
5. Ster C, Lebeau V, Leclerc J, Fugère A, Veh KA, Roy JP, et al. In vitro antibiotic susceptibility and biofilm production of Staphylococcus aureus isolates recovered from bovine intramammary infections that persisted or not following extended therapies with cephapirin, pirlimycin or ceftiofur. Vet Res. 2017;48(1) 56. doi: 10.1186/s13567-017-0463-0 28934980
6. Jamali H, Barkema HW, Jacques M, Lavallée-Bourget E-M, Malouin F, Saini V, et al. Invited review: Incidence, risk factors, and effects of clinical mastitis recurrence in dairy cows. J Dairy Sci. 2018;101: 4729–4746. doi: 10.3168/jds.2017-13730 29525302
7. Aghamohammadi M, Haine D, Kelton DF, Barkema HW, Hogeveen H, Keefe GP, et al. Herd-Level Mastitis-Associated Costs on Canadian Dairy Farms. Front Vet Sci. 2018;5: 100. doi: 10.3389/fvets.2018.00100 29868620
8. Côté-gravel J, Malouin F. Symposium review: Features of Staphylococcus aureus mastitis pathogenesis that guide vaccine development strategies. J Dairy Sci. 2019;102: 4727–4740. doi: 10.3168/jds.2018-15272 30580940
9. Middleton JR, Ma J, Rinehart CL, Taylor VN, Luby CD, Steevens BJ. Efficacy of different Lysigin formulations in the prevention of Staphylococcus aureus intramammary infection in dairy heifers. J Dairy Res. 2006;73: 10–19. doi: 10.1017/S0022029905001354 16433956
10. Prenafeta A, March R, Foix A, Casals I, Costa L. Study of the humoral immunological response after vaccination with a Staphylococcus aureus biofilm-embedded bacterin in dairy cows: possible role of the exopolysaccharide specific antibody production in the protection from Staphylococcus aureus induced mastitis. Vet Immunol Immunopathol. 2010;134: 208–217. doi: 10.1016/j.vetimm.2009.09.020 19836084
11. Piepers S, Prenafeta A, Verbeke J, De Visscher A, March R, De Vliegher S. Immune response after an experimental intramammary challenge with killed Staphylococcus aureus in cows and heifers vaccinated and not vaccinated with Startvac, a polyvalent mastitis vaccine. J Dairy Sci. 2017;100: 769–782. doi: 10.3168/jds.2016-11269 27816241
12. Middleton JR, Luby CD, Adams DS. Efficacy of vaccination against staphylococcal mastitis: a review and new data. Vet Microbiol. 2009;134: 192–198. doi: 10.1016/j.vetmic.2008.09.053 19010613
13. Spellberg B, Daum R. Development of a vaccine against Staphylococcus aureus. Semin Immunopathol. 2012;34: 335–348. doi: 10.1007/s00281-011-0293-5 22080194
14. Kahl BC. Small colony variants (SCVs) of Staphylococcus aureus—a bacterial survival strategy. Infect Genet Evol. 2014;21: 515–522. doi: 10.1016/j.meegid.2013.05.016 23722021
15. Proctor RA, von Eiff C, Kahl BC, Becker K, McNamara P, Herrmann M, et al. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol. 2006;4: 295–305. doi: 10.1038/nrmicro1384 16541137
16. Mitchell G, Séguin DL, Asselin A, Déziel E, Cantin AM, Frost EH, et al. Staphylococcus aureus sigma B-dependent emergence of small-colony variants and biofilm production following exposure to Pseudomonas aeruginosa 4-hydroxy-2-heptylquinoline-N-oxide. BMC Microbiol. 2010;10: 33. doi: 10.1186/1471-2180-10-33 20113519
17. Singh R, Ray P, Das A, Sharma M. Enhanced production of exopolysaccharide matrix and biofilm by a menadione-auxotrophic Staphylococcus aureus small-colony variant. J Med Microbiol. 2010;59: 521–527. doi: 10.1099/jmm.0.017046-0 20110391
18. Kalinka J, Hachmeister M, Geraci J, Sordelli D, Hansen U, Niemann S, et al. Staphylococcus aureus isolates from chronic osteomyelitis are characterized by high host cell invasion and intracellular adaptation, but still induce inflammation. Int J Med Microbiol. 2014;304(8): 1038–1049. doi: 10.1016/j.ijmm.2014.07.013 25129555
19. Löffler B, Tuchscherr L, Niemann S, Peters G. Staphylococcus aureus persistence in non-professional phagocytes. Int J Med Microbiol. 2014;304: 170–176. doi: 10.1016/j.ijmm.2013.11.011 24365645
20. Atalla H, Gyles C, Mallard B. Persistence of a Staphylococcus aureus small colony variants (S. aureus SCV) within bovine mammary epithelial cells. Vet Microbiol. 2010;143: 319–328. doi: 10.1016/j.vetmic.2009.11.030 20022186
21. Atalla H, Gyles C, Jacob CL, Moisan H, Malouin F, Mallard B. Characterization of a Staphylococcus aureus small colony variant (SCV) associated with persistent bovine mastitis. Foodborne pathogens and disease. 2008;5: 785–799. doi: 10.1089/fpd.2008.0110 19014276
22. Roy J-P, Keefe G. Systematic review: what is the best antibiotic treatment for Staphylococcus aureus intramammary infection of lactating cows in North America? Vet Clin Food Anim. 2012;28: 39–50. doi: 10.1016/j.cvfa.2011.12.004 22374116
23. Von Eiff C, Heilmann C, Proctor RA, Woltz C, Peters G, Go F. A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly. J Bacteriol. 1997;179(15): 4706–4712. doi: 10.1128/jb.179.15.4706-4712.1997 9244256
24. Côté-Gravel J, Brouillette E, Obradović N, Ster C, Talbot BG, Malouin F. Characterization of a vraG mutant in a genetically stable Staphylococcus aureus small-colony variant and preliminary assessment for use as a live-attenuated vaccine against intrammamary infections. PLoS One. 2016;11: e0166621. doi: 10.1371/journal.pone.0166621 27855187
25. Allard M, Ster C, Jacob CL, Scholl D, Diarra MS, Lacasse P, et al. The expression of a putative exotoxin and an ABC transporter during bovine intramammary infection contributes to the virulence of Staphylococcus aureus. Vet Microbiol. 2013;162: 761–770. doi: 10.1016/j.vetmic.2012.09.029 23116586
26. Barbet G, Sander LE, Geswell M, Leonardi I, Cerutti A, Iliev I. Sensing Microbial Viability through Bacterial RNA Augments T Follicular Helper Cell and Antibody Responses. Immunity. 2018;48: 584–598. doi: 10.1016/j.immuni.2018.02.015 29548673
27. Mutharia LM, Crockford G, Bogard WC, Hancock REW. Monoclonal Antibodies Specific for Escherichia coli J5 Lipopolysaccharide: Cross-reaction with Other Gram-Negative Bacterial Species. Infect Immun. 1984;45: 631–636. 6381310
28. Asli A, Brouillette E, Krause KM, Nichols WW, Malouin F. Distinctive Binding of Avibactam to Penicillin-Binding Proteins of Gram-Negative and Gram-Positive Bacteria. Antimicrob Agents Chemother. 2016;60: 752–756. doi: 10.1128/AAC.02102-15 26574008
29. Maassen CBM, Boersma WJA, Van Holten-Neelen C, Claassen E, Laman JD. Growth phase of orally administered Lactobacillus strains differentially affects IgG1/IgG2a ratio for soluble antigens: implications for vaccine development. Vaccine. 2003;21: 2751–2757. doi: 10.1016/s0264-410x(03)00220-2 12798614
30. Zhang F, Ledue O, Jun M, Goulart C, Malley R, Lu Y-J. Protection against Staphylococcus aureus Colonization and Infection by B-and T-Cell-Mediated Mechanisms. MBio. 2018;9: e01949–18. doi: 10.1128/mBio.01949-18 30327437
31. Rainard P, Foucras G, Fitzgerald JR, Watts JL, Koop G, Middleton JR. Knowledge gaps and research priorities in Staphylococcus aureus mastitis control. Transbound Emerg Dis. 2017;65: 149–165. doi: 10.1111/tbed.12698 28984427
32. Montgomery CP, Daniels M, Zhao F, Alegre M-L, Chong AS, Daum RS. Protective immunity against recurrent Staphylococcus aureus skin infection requires antibody and interleukin-17A. Infect Immun. 2014;82: 2125–2134. doi: 10.1128/IAI.01491-14 24614654
33. Ferraro A, Buonocore SM, Auquier P, Nicolas I, Wallemacq H, Boutriau D, et al. Role and plasticity of Th1 and Th17 responses in immunity to Staphylococcus aureus. Hum Vaccin Immunother. 2019. doi: 10.1080/21645515.2019.1613126 31149870
34. Lin IYC, Van TTH, Smooker PM. Live-attenuated bacterial vectors: Tools for vaccine and therapeutic agent delivery. Vaccines. 2015;3(4):940–972. doi: 10.3390/vaccines3040940 26569321
35. Cha E, Bar D, Hertl JA, Tauer LW, Bennett G, González RN, et al. The cost and management of different types of clinical mastitis in dairy cows estimated by dynamic programming. J Dairy Sci. 2011;94: 4476–4487. doi: 10.3168/jds.2010-4123 21854920
36. Bradley AJ, Breen JE, Payne B, White V, Green MJ. An investigation of the efficacy of a polyvalent mastitis vaccine using different vaccination regimens under field conditions in the United Kingdom. J Dairy Sci. 2015;98: 1706–1720. doi: 10.3168/jds.2014-8332 25529419
37. Landin H, Mörk MJ, Larsson M, Waller KP. Vaccination against Staphylococcus aureus mastitis in two Swedish dairy herds. Acta Vet Scand. 2015;57: 81. doi: 10.1186/s13028-015-0171-6 26608421
38. Jensen K, Günther J, Talbot R, Petzl W, Zerbe H, Schuberth HJ, et al. Escherichia coli- and Staphylococcus aureus-induced mastitis differentially modulate transcriptional responses in neighbouring uninfected bovine mammary gland quarters. BMC Genomics. 2013;14: 36. doi: 10.1186/1471-2164-14-36 23324411
39. Younis S, Javed Q, Blumenberg M. Meta-analysis of transcriptional responses to mastitis-causing Escherichia coli. PLoS One. 2016;11(3): e0148562. doi: 10.1371/journal.pone.0148562 26933871
40. Ezzat Alnakip M, Quintela-Baluja M, Böhme K, Fernández-No I, Caamaño-Antelo S, Calo-Mata P, et al. The Immunology of Mammary Gland of Dairy Ruminants between Healthy and Inflammatory Conditions. J Vet Med. 2014;2014: 659801. doi: 10.1155/2014/659801 26464939
41. Günther J, Petzl W, Bauer I, Ponsuksili S, Zerbe H, Schuberth HJ, et al. Differentiating Staphylococcus aureus from Escherichia coli mastitis: S. aureus triggers unbalanced immune-dampening and host cell invasion immediately after udder infection. Sci Rep. 2017;7: 4811. doi: 10.1038/s41598-017-05107-4 28684793
42. Rainard P, Cunha P, Bougarn S, Fromageau A, Rossignol C, Gilbert FB, et al. T helper 17-associated cytokines are produced during antigen-specific inflammation in the mammary gland. PLoS One. 2013;8: e63471. doi: 10.1371/journal.pone.0063471 23696826
43. Misra N, Wines TF, Knopp CL, Hermann R, Bond L, Mitchell B, et al. Immunogenicity of a Staphylococcus aureus-cholera toxin A2/B vaccine for bovine mastitis. Vaccine. 2018;36: 3513–3521. doi: 10.1016/j.vaccine.2018.04.067 29739718
44. Mutwiri G, Gerdts V, van Drunen Littel-van den Hurk S, Auray G, Eng N, Garlapati S, et al. Combination adjuvants: the next generation of adjuvants? Expert Rev Vaccines. 2011;10: 95–107. doi: 10.1586/erv.10.154 21162624
45. Mancini F, Monaci E, Lofano G, Torre A. One Dose of Staphylococcus aureus 4C-Staph Vaccine Formulated with a Novel TLR7- Dependent Adjuvant Rapidly Protects Mice through Antibodies, Effector CD4+ T Cells, and IL-17A. PLoS One. 2016;11: e0147767. doi: 10.1371/journal.pone.0147767 26812180
46. Ugolini M, Gerhard J, Burkert S, Jensen KJ, Georg P, Ebner F, et al. Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses. Nat Immunol. 2018;19: 386–396. doi: 10.1038/s41590-018-0068-4 29556002
47. Ueno H, Banchereau J, Vinuesa CG. Pathophysiology of T follicular helper cells in humans and mice. Nat Immunol. 2015;16: 142–152. doi: 10.1038/ni.3054 25594465
48. Galen JE, Curtiss R. The delicate balance in genetically engineering live vaccines. Vaccine. 2014;32: 4376–4385. doi: 10.1016/j.vaccine.2013.12.026 24370705
49. Falord M, Karimova G, Hiron A, Msadek T. GraXSR Interact With The VraFG ABC Transporter to Form a Five-Component System Required for Cationic Antimicrobial Peptide Sensing and Resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 2012;56: 1047–1058. doi: 10.1128/AAC.05054-11 22123691
50. Yang S-J, Bayer AS, Mishra NN, Meehl M, Ledala N, Yeaman MR, et al. The Staphylococcus aureus two-component regulatory system, GraRS, senses and confers resistance to selected cationic antimicrobial peptides. Infect Immun. 2012;80: 74–81. doi: 10.1128/IAI.05669-11 21986630
51. Falord M, Mäder U, Hiron A, Débarbouillé M, Msadek T. Investigation of the Staphylococcus aureus GraSR Regulon Reveals Novel Links to Virulence, Stress Response and Cell Wall Signal Transduction Pathways. PLoS One. 2011;6: e21323. doi: 10.1371/journal.pone.0021323 21765893
52. Tuchscherr L, Löffler B. Staphylococcus aureus dynamically adapts global regulators and virulence factor expression in the course from acute to chronic infection. Curr Genet. 2016;62 15–17. doi: 10.1007/s00294-015-0503-0 26123224
53. Mitchell G, Lamontagne C-A, Brouillette E, Grondin G, Talbot BG, Grandbois M, et al. Staphylococcus aureus SigB activity promotes a strong fibronectin-bacterium interaction which may sustain host tissue colonization by small-colony variants isolated from cystic fibrosis patients. Mol Microbiol. 2008;70: 1540–1555. doi: 10.1111/j.1365-2958.2008.06511.x 19007412
54. Tamber S, Cheung AL. SarZ promotes the expression of virulence factors and represses biofilm formation by modulating SarA and agr in Staphylococcus aureus. Infect Immun. 2009;77: 419–428. doi: 10.1128/IAI.00859-08 18955469
55. Tuchscherr L, Medina E, Hussain M, Völker W, Heitmann V, Niemann S, et al. Staphylococcus aureus phenotype switching: an effective bacterial strategy to escape host immune response and establish a chronic infection. EMBO Mol Med. 2011;3: 129–141. doi: 10.1002/emmm.201000115 21268281
56. Martínez-Pulgarín S, Domínguez-Bernal G, Orden JA, de la Fuente R. Simultaneous lack of catalase and beta-toxin in Staphylococcus aureus leads to increased intracellular survival in macrophages and epithelial cells and to attenuated virulence in murine and ovine models. Microbiology. 2009;155: 1505–1515. doi: 10.1099/mic.0.025544-0 19383704
Článok vyšiel v časopise
PLOS One
2019 Číslo 12
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Těžké menstruační krvácení může značit poruchu krevní srážlivosti. Jaký management vyšetření a léčby je v takovém případě vhodný?
- Fixní kombinace paracetamol/kodein nabízí synergické analgetické účinky
Najčítanejšie v tomto čísle
- Methylsulfonylmethane increases osteogenesis and regulates the mineralization of the matrix by transglutaminase 2 in SHED cells
- Oregano powder reduces Streptococcus and increases SCFA concentration in a mixed bacterial culture assay
- The characteristic of patulous eustachian tube patients diagnosed by the JOS diagnostic criteria
- Parametric CAD modeling for open source scientific hardware: Comparing OpenSCAD and FreeCAD Python scripts