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Exploitation of Reporter Strains to Probe the Impact of Vaccination at Sites of Infection


Mycobacterium tuberculosis (Mtb) remains a serious challenge to global health, a situation that is exacerbated by emerging drug resistance, the paucity of new antibiotics, and the absence of an effective vaccine. Whilst there is no doubt that an anti-tuberculosis vaccine would have an extraordinary impact on the control of this disease, it is not clear if such a goal is achievable. One major deficiency in our knowledge is an appreciation of how the same protective immune response that limits bacterial growth is also responsible for driving adaptation of Mtb towards successful maintenance of long-term infection. We have used our panel of reporter Mtb strains that fluoresce under different environmental stresses for experimental infections of naïve and vaccinated, wild type and immune-deficient, mouse strains. In addition, we utilized a novel replication reporter strain to visualize the distribution of replicating versus non-replicating bacteria within infected lung tissue. The data provide novel insights into how the host immune response impacts bacterial fitness, physiology, and growth rates during the course of infection in naïve and vaccinated mice.


Vyšlo v časopise: Exploitation of Reporter Strains to Probe the Impact of Vaccination at Sites of Infection. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004394
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004394

Souhrn

Mycobacterium tuberculosis (Mtb) remains a serious challenge to global health, a situation that is exacerbated by emerging drug resistance, the paucity of new antibiotics, and the absence of an effective vaccine. Whilst there is no doubt that an anti-tuberculosis vaccine would have an extraordinary impact on the control of this disease, it is not clear if such a goal is achievable. One major deficiency in our knowledge is an appreciation of how the same protective immune response that limits bacterial growth is also responsible for driving adaptation of Mtb towards successful maintenance of long-term infection. We have used our panel of reporter Mtb strains that fluoresce under different environmental stresses for experimental infections of naïve and vaccinated, wild type and immune-deficient, mouse strains. In addition, we utilized a novel replication reporter strain to visualize the distribution of replicating versus non-replicating bacteria within infected lung tissue. The data provide novel insights into how the host immune response impacts bacterial fitness, physiology, and growth rates during the course of infection in naïve and vaccinated mice.


Zdroje

1. da CostaAC, NogueiraSV, KipnisA, Junqueira-KipnisAP (2014) Recombinant BCG: Innovations on an Old Vaccine. Scope of BCG Strains and Strategies to Improve Long-Lasting Memory. Front Immunol 5: 152.

2. SableSB, CheruvuM, NandakumarS, SharmaS, BandyopadhyayK, et al. (2011) Cellular immune responses to nine Mycobacterium tuberculosis vaccine candidates following intranasal vaccination. PLoS ONE 6: e22718.

3. BertholetS, IretonGC, OrdwayDJ, WindishHP, PineSO, et al. (2010) A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis. Sci Transl Med 2: 53ra74.

4. AagaardC, HoangT, DietrichJ, CardonaPJ, IzzoA, et al. (2011) A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med 17: 189–194.

5. OrmeIM (2013) Vaccine development for tuberculosis: current progress. Drugs 73: 1015–1024.

6. KaufmannSH (2013) Tuberculosis vaccines: time to think about the next generation. Semin Immunol 25: 172–181.

7. TamerisMD, HatherillM, LandryBS, ScribaTJ, SnowdenMA, et al. (2013) Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet 381: 1021–1028.

8. NorthRJ, JungYJ (2004) Immunity to tuberculosis. Annu Rev Immunol 22: 599–623.

9. RussellDG (2007) Who puts the tubercle in tuberculosis? Nat Rev Microbiol 5: 39–47.

10. RussellDG, BarryCE3rd, FlynnJL (2010) Tuberculosis: what we don't know can, and does, hurt us. Science 328: 852–856.

11. GideonHP, FlynnJL (2011) Latent tuberculosis: what the host “sees”? Immunol Res 50: 202–212.

12. GlaziouP, FalzonD, FloydK, RaviglioneM (2013) Global epidemiology of tuberculosis. Semin Respir Crit Care Med 34: 3–16.

13. FlynnJL, ChanJ (2005) What's good for the host is good for the bug. Trends Microbiol 13: 98–102.

14. RussellDG (2013) The evolutionary pressures that have molded Mycobacterium tuberculosis into an infectious adjuvant. Curr Opin Microbiol 16: 78–84.

15. LinPL, FordCB, ColemanMT, MyersAJ, GawandeR, et al. (2013) Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing. Nat Med 20: 75–79.

16. ViaLE, SchimelD, WeinerDM, DartoisV, DayaoE, et al. (2012) Infection dynamics and response to chemotherapy in a rabbit model of tuberculosis using [(1)(8)F]2-fluoro-deoxy-D-glucose positron emission tomography and computed tomography. Antimicrob Agents Chemother 56: 4391–4402.

17. TanS, SukumarN, AbramovitchRB, ParishT, RussellDG (2013) Mycobacterium tuberculosis responds to chloride and pH as synergistic cues to the immune status of its host cell. PLoS Pathog 9: e1003282.

18. GillWP, HarikNS, WhiddonMR, LiaoRP, MittlerJE, et al. (2009) A replication clock for Mycobacterium tuberculosis. Nat Med 15: 211–214.

19. RohdeKH, VeigaDF, CaldwellS, BalazsiG, RussellDG (2012) Linking the transcriptional profiles and the physiological states of Mycobacterium tuberculosis during an extended intracellular infection. PLoS Pathog 8: e1002769.

20. FlynnJL, ChanJ (2001) Immunology of tuberculosis. Annu Rev Immunol 19: 93–129.

21. OhnoH, ZhuG, MohanVP, ChuD, KohnoS, et al. (2003) The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis. Cell Microbiol 5: 637–648.

22. VoskuilMI, SchnappingerD, ViscontiKC, HarrellMI, DolganovGM, et al. (2003) Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J Exp Med 198: 705–713.

23. KumarA, ToledoJC, PatelRP, LancasterJRJr, SteynAJ (2007) Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Proc Natl Acad Sci U S A 104: 11568–11573.

24. ParkHD, GuinnKM, HarrellMI, LiaoR, VoskuilMI, et al. (2003) Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis. Mol Microbiol 48: 833–843.

25. MacMickingJD, NorthRJ, LaCourseR, MudgettJS, ShahSK, et al. (1997) Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc Natl Acad Sci U S A 94: 5243–5248.

26. ScangaCA, MohanVP, TanakaK, AllandD, FlynnJL, et al. (2001) The inducible nitric oxide synthase locus confers protection against aerogenic challenge of both clinical and laboratory strains of Mycobacterium tuberculosis in mice. Infect Immun 69: 7711–7717.

27. CooperAM, DaltonDK, StewartTA, GriffinJP, RussellDG, et al. (1993) Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med 178: 2243–2247.

28. FlynnJL, ChanJ, TrieboldKJ, DaltonDK, StewartTA, et al. (1993) An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178: 2249–2254.

29. CowleySC, ElkinsKL (2003) CD4+ T cells mediate IFN-gamma-independent control of Mycobacterium tuberculosis infection both in vitro and in vivo. J Immunol 171: 4689–4699.

30. Reyes-LamotheR, PossozC, DanilovaO, SherrattDJ (2008) Independent positioning and action of Escherichia coli replisomes in live cells. Cell 133: 90–102.

31. BerkmenMB, GrossmanAD (2006) Spatial and temporal organization of the Bacillus subtilis replication cycle. Mol Microbiol 62: 57–71.

32. CostesA, LecointeF, McGovernS, Quevillon-CheruelS, PolardP (2010) The C-terminal domain of the bacterial SSB protein acts as a DNA maintenance hub at active chromosome replication forks. PLoS Genet 6: e1001238.

33. GomezJE, McKinneyJD (2004) M. tuberculosis persistence, latency, and drug tolerance. Tuberculosis (Edinb) 84: 29–44.

34. WayneLG, SohaskeyCD (2001) Nonreplicating persistence of mycobacterium tuberculosis. Annu Rev Microbiol 55: 139–163.

35. KarakousisPC, YoshimatsuT, LamichhaneG, WoolwineSC, NuermbergerEL, et al. (2004) Dormancy phenotype displayed by extracellular Mycobacterium tuberculosis within artificial granulomas in mice. J Exp Med 200: 647–657.

36. TanejaNK, DhingraS, MittalA, NareshM, TyagiJS (2010) Mycobacterium tuberculosis transcriptional adaptation, growth arrest and dormancy phenotype development is triggered by vitamin C. PLoS ONE 5: e10860.

37. CarrollP, SchreuderLJ, Muwanguzi-KarugabaJ, WilesS, RobertsonBD, et al. (2010) Sensitive detection of gene expression in mycobacteria under replicating and non-replicating conditions using optimized far-red reporters. PLoS ONE 5: e9823.

38. AldridgeBB, Fernandez-SuarezM, HellerD, AmbravaneswaranV, IrimiaD, et al. (2012) Asymmetry and aging of mycobacterial cells lead to variable growth and antibiotic susceptibility. Science 335: 100–104.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


2014 Číslo 9
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