Strain-Specific Differences in the Genetic Control of Two Closely Related Mycobacteria

English version České info

The host response to mycobacterial infection depends on host and pathogen genetic factors. Recent studies in human populations suggest a strain specific genetic control of tuberculosis. To test for mycobacterial-strain specific genetic control of susceptibility to infection under highly controlled experimental conditions, we performed a comparative genetic analysis using the A/J- and C57BL/6J-derived recombinant congenic (RC) mouse panel infected with the Russia and Pasteur strains of Mycobacterium bovis Bacille Calmette Guérin (BCG). Bacillary counts in the lung and spleen at weeks 1 and 6 post infection were used as a measure of susceptibility. By performing genome-wide linkage analyses of loci that impact on tissue-specific bacillary burden, we were able to show the importance of correcting for strain background effects in the RC panel. When linkage analysis was adjusted on strain background, we detected a single locus on chromosome 11 that impacted on pulmonary counts of BCG Russia but not Pasteur. The same locus also controlled the splenic counts of BCG Russia but not Pasteur. By contrast, a locus on chromosome 1 which was indistinguishable from Nramp1 impacted on splenic bacillary counts of both BCG Russia and Pasteur. Additionally, dependent upon BCG strain, tissue and time post infection, we detected 9 distinct loci associated with bacillary counts. Hence, the ensemble of genetic loci impacting on BCG infection revealed a highly dynamic picture of genetic control that reflected both the course of infection and the infecting strain. This high degree of adaptation of host genetics to strain-specific pathogenesis is expected to provide a suitable framework for the selection of specific host-mycobacteria combinations during co-evolution of mycobacteria with humans.

Vyšlo v časopise: Strain-Specific Differences in the Genetic Control of Two Closely Related Mycobacteria. PLoS Pathog 6(10): e32767. doi:10.1371/journal.ppat.1001169
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001169

Souhrn

Zdroje

1. NgVH

CoxJS

SousaAO

MacMickingJD

McKinneyJD

2004 Role of KatG catalase-peroxidase in mycobacterial pathogenesis: countering the phagocyte oxidative burst. Mol Microbiol 52 1291 1302

2. DarwinKH

EhrtS

Gutierrez-RamosJC

WeichN

NathanCF

2003 The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 302 1963 1966

3. TobinDM

VaryJCJr

RayJP

WalshGS

DunstanSJ

2010 The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell 140 717 730

4. DivangahiM

ChenM

GanH

DesjardinsD

HickmanTT

2009 Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair. Nat Immunol 10 899 906

5. GanH

LeeJ

RenF

ChenM

KornfeldH

2008 Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence. Nat Immunol 9 1189 1197

6. ChenM

DivangahiM

GanH

ShinDS

HongS

2008 Lipid mediators in innate immunity against tuberculosis: opposing roles of PGE2 and LXA4 in the induction of macrophage death. J Exp Med 205 2791 2801

7. BehrM

SchurrE

GrosP

2010 TB: screening for responses to a vile visitor. Cell 140 615 618

8. GagneuxS

SmallPM

2007 Global phylogeography of Mycobacterium tuberculosis and implications for tuberculosis product development. Lancet Infect Dis 7 328 337

9. NicolMP

WilkinsonRJ

2008 The clinical consequences of strain diversity in Mycobacterium tuberculosis. Trans R Soc Trop Med Hyg 102 955 965

10. GagneuxS

DeRiemerK

VanT

Kato-MaedaM

de JongBC

2006 Variable host-pathogen compatibility in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 103 2869 2873

11. ReedMB

PichlerVK

McIntoshF

MattiaA

FallowA

2009 Major Mycobacterium tuberculosis lineages associate with patient country of origin. J Clin Microbiol 47 1119 1128

12. CawsM

ThwaitesG

DunstanS

HawnTR

LanNT

2008 The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis. PLoS Pathog 4 e1000034

13. HerbF

ThyeT

NiemannS

BrowneEN

ChinbuahMA

2008 ALOX5 variants associated with susceptibility to human pulmonary tuberculosis. Hum Mol Genet 17 1052 1060

14. IntemannCD

ThyeT

NiemannS

BrowneEN

Amanua ChinbuahM

2009 Autophagy gene variant IRGM -261T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains. PLoS Pathog 5 e1000577

15. BehrMA

SmallPM

1999 A historical and molecular phylogeny of BCG strains. Vaccine 17 915 922

16. CalmetteA

GuérinC

BretonM

1907 Contribution à l'étude de la tuberculose expérimentale du cobaye. Ann Inst Pasteur 401 416

17. OettingerT

JorgensenM

LadefogedA

HaslovK

AndersenP

1999 Development of the Mycobacterium bovis BCG vaccine: review of the historical and biochemical evidence for a genealogical tree. Tuber Lung Dis 79 243 250

18. LewisKN

LiaoR

GuinnKM

HickeyMJ

SmithS

2003 Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guerin attenuation. J Infect Dis 187 117 123

19. PymAS

BrodinP

BroschR

HuerreM

ColeST

2002 Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. Mol Microbiol 46 709 717

20. MostowyS

TsolakiAG

SmallPM

BehrMA

2003 The in vitro evolution of BCG vaccines. Vaccine 21 4270 4274

21. KellerPM

BottgerEC

SanderP

2008 Tuberculosis vaccine strain Mycobacterium bovis BCG Russia is a natural recA mutant. BMC Microbiol 8 120

22. BroschR

GordonSV

GarnierT

EiglmeierK

FriguiW

2007 Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci U S A 104 5596 5601

23. BehrMA

SchroederBG

BrinkmanJN

SlaydenRA

BarryCE

3rd

2000 A point mutation in the mma3 gene is responsible for impaired methoxymycolic acid production in Mycobacterium bovis BCG strains obtained after 1927. J Bacteriol 182 3394 3399

24. MahairasGG

SaboPJ

HickeyMJ

SinghDC

StoverCK

1996 Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J Bacteriol 178 1274 1282

25. SalamonH

Kato-MaedaM

SmallPM

DrenkowJ

GingerasTR

2000 Detection of deleted genomic DNA using a semiautomated computational analysis of GeneChip data. Genome Res 10 2044 2054

26. CharletD

MostowyS

AlexanderD

SitL

WikerHG

2005 Reduced expression of antigenic proteins MPB70 and MPB83 in Mycobacterium bovis BCG strains due to a start codon mutation in sigK. Mol Microbiol 56 1302 1313

27. SpreadburyCL

PallenMJ

OvertonT

BehrMA

MostowyS

2005 Point mutations in the DNA- and cNMP-binding domains of the homologue of the cAMP receptor protein (CRP) in Mycobacterium bovis BCG: implications for the inactivation of a global regulator and strain attenuation. Microbiology 151 547 556

28. BlackGF

WeirRE

FloydS

BlissL

WarndorffDK

2002 BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies. Lancet 359 1393 1401

29. LalorMK

Ben-SmithA

Gorak-StolinskaP

WeirRE

FloydS

2009 Population Differences in Immune Responses to Bacille Calmette-Guerin Vaccination in Infancy. J Infect Dis 199 795 800

30. WuB

HuangC

GarciaL

Ponce de LeonA

OsornioJS

2007 Unique gene expression profiles in infants vaccinated with different strains of Mycobacterium bovis bacille Calmette-Guerin. Infect Immun 75 3658 3664

31. LiuJ

TranV

LeungAS

AlexanderDC

ZhuB

2009 BCG vaccines: their mechanisms of attenuation and impact on safety and protective efficacy. Hum Vaccin 5 70 78

32. TrunzBB

FineP

DyeC

2006 Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet 367 1173 1180

33. DemantP

HartAA

1986 Recombinant congenic strains—a new tool for analyzing genetic traits determined by more than one gene. Immunogenetics 24 416 422

34. FortinA

DiezE

RochefortD

LarocheL

MaloD

2001 Recombinant congenic strains derived from A/J and C57BL/6J: a tool for genetic dissection of complex traits. Genomics 74 21 35

35. GrosP

SkameneE

ForgetA

1981 Genetic control of natural resistance to Mycobacterium bovis (BCG) in mice. J Immunol 127 2417 2421

36. BelleyA

AlexanderD

Di PietrantonioT

GirardM

JonesJ

2004 Impact of methoxymycolic acid production by Mycobacterium bovis BCG vaccines. Infect Immun 72 2803 2809

37. Mouse Genome Database (MGD) at the Mouse Genome Informatics website TJL, Bar Harbor, Maine

38. VidalSM

MaloD

VoganK

SkameneE

GrosP

1993 Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 73 469 485

39. MullerovaJ

HozakP

2004 Use of recombinant congenic strains in mapping disease-modifying genes. News Physiol Sci 19 105 109

40. Min-OoG

FortinA

TamMF

NantelA

StevensonMM

2003 Pyruvate kinase deficiency in mice protects against malaria. Nat Genet 35 357 362

41. RoyMF

RiendeauN

BedardC

HelieP

Min-OoG

2007 Pyruvate kinase deficiency confers susceptibility to Salmonella typhimurium infection in mice. J Exp Med 204 2949 2961

42. CamaterosP

MarinoR

FortinA

MartinJG

SkameneE

2010 Identification of novel chromosomal regions associated with airway hyperresponsiveness in recombinant congenic strains of mice. Mamm Genome 21 28 38

43. SchurrE

KramnikI

2008 Genetic control of host susceptibility to tuberculosis.

KaufmannS

BrittenW

Handbook of Tuberculosis Weinheim, Germany Wiley-VCH 305 346

44. GreenwoodCM

FujiwaraTM

BoothroydLJ

MillerMA

FrappierD

2000 Linkage of tuberculosis to chromosome 2q35 loci, including NRAMP1, in a large aboriginal Canadian family. Am J Hum Genet 67 405 416