Molecular basis of the defective heat stress response in Mycobacterium leprae.
Mycobacterium leprae, a major human pathogen, grows poorly at 37 degrees C. The basis for its inability to survive at elevated temperatures was investigated. We determined that M. leprae lacks a protective heat shock response as a result of the lack of transcriptional induction of the alternative sigma factor genes sigE and sigB and the major heat shock operons, HSP70 and HSP60, even though heat shock promoters and regulatory circuits for these genes appear to be intact. M. leprae sigE was found to be capable of complementing the defective heat shock response of mycobacterial sigE knockout mutants only in the presence of a functional mycobacterial sigH, which orchestrates the mycobacterial heat shock response. Since the sigH of M. leprae is a pseudogene, these data support the conclusion that a key aspect of the defective heat shock response in M. leprae is the absence of a functional sigH. In addition, 68% of the genes induced during heat shock in M. tuberculosis were shown to be either absent from the M. leprae genome or were present as pseudogenes. Among these is the hsp/acr2 gene, whose product is essential for M. tuberculosis survival during heat shock. Taken together, these results suggest that the reduced ability of M. leprae to survive at elevated temperatures results from the lack of a functional transcriptional response to heat shock and the absence of a full repertoire of heat stress response genes, including sigH.
Williams
Diana L
DL
Molecular Biology Research Dept., Laboratory Research Branch, Division of the National Hansen's Disease Programs at LSU-SVM, Baton Rouge, LA 70803, USA. dwill21@lsu.edu
Pittman
Tana L
TL
Deshotel
Mike
M
Oby-Robinson
Sandra
S
Smith
Issar
I
Husson
Robert
R
D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics*; D018834:Chaperonin 60 / Q000096:biosynthesis; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D018882:Heat Stress Disorders; D006358:Hot Temperature; D009166:Mycobacterium leprae / Q000235:genetics / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000502:physiology; D011544:Pseudogenes; D012808:Sigma Factor / Q000096:biosynthesis / Q000235:genetics*; D038201:alpha-Crystallins / Q000235:genetics / Q000502:physiology
D001426:Bacterial Proteins; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; C079011:SigB protein, Bacteria; C120328:SigH protein, bacteria; D012808:Sigma Factor; D038201:alpha-Crystallins; C500452:alpha-crystallin 2, Mycobacterium tuberculosis; C111259:sigE protein, Bacteria