Genetic requirements for the survival of tubercle bacilli in primates.
BACKGROUND
Tuberculosis (TB) leads to the death of 1.7 million people annually. The failure of the bacille Calmette-Guérin vaccine, synergy between AIDS and TB, and the emergence of drug resistance have worsened this situation. It is imperative to delineate the mechanisms employed by Mycobacterium tuberculosis to successfully infect and persist in mammalian lungs.


METHODS
Nonhuman primates (NHPs) are arguably the best animal system to model critical aspects of human TB. We studied genes essential for growth and survival of M. tuberculosis in the lungs of NHPs experimentally exposed to aerosols of an M. tuberculosis transposon mutant library.


RESULTS
Mutants in 108 M. tuberculosis genes (33.13% of all genes tested) were attenuated for in vivo growth. Comparable studies have reported the attenuation of only approximately 6% of mutants in mice. The M. tuberculosis mutants attenuated for in vivo survival in primates were involved in the transport of various biomolecules, including lipid virulence factors; biosynthesis of cell-wall arabinan and peptidoglycan; DNA repair; sterol metabolism; and mammalian cell entry.


CONCLUSIONS
Our study highlights the various virulence mechanisms employed by M. tuberculosis to overcome the hostile environment encountered during infection of primates. Prophylactic approaches aimed against bacterial factors that respond to such in vivo stressors have the potential to prevent infection at an early stage, thus likely reducing the extent of transmission of M. tuberculosis.
Dutta
Noton K
NK
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
Mehra
Smriti
S
Didier
Peter J
PJ
Roy
Chad J
CJ
Doyle
Lara A
LA
Alvarez
Xavier
X
Ratterree
Marion
M
Be
Nicholas A
NA
Lamichhane
Gyanu
G
Jain
Sanjay K
SK
Lacey
Michelle R
MR
Lackner
Andrew A
AA
Kaushal
Deepak
D
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D008253:Macaca mulatta / Q000382:microbiology*; D008297:Male; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity*; D014376:Tuberculosis / Q000382:microbiology* / Q000473:pathology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
D001426:Bacterial Proteins; D037521:Virulence Factors
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