Mycobacterium tuberculosis modulates its cell surface via an oligopeptide permease (Opp) transport system.
Bacterial species utilize a vast repertoire of surface structures to interact with their surroundings and employ a number of strategies to reconfigure the cellular envelope according to specific stimuli. Gram-positive bacteria, exemplified by Streptomyces and Bacillus species, control production of some exposed molecules by importing oligopeptide signals via permeases (Opp). Such oligopeptides modulate intracellular signaling pathways. In this work, we functionally characterized an Opp of the human pathogen Mycobacterium tuberculosis (Mtb) and propose its reannotation. Using genome-wide transcriptional profiling, we found that Opp was required to modulate (fold-change ranging from -3.5 to 2.0) the expression of several genes, most of them encoding surface-exposed molecules. These included the virulence-associated lipids mycolic acids and phthiocerol dimycocerosates (PDIMs) as well as PE-family proteins. By thin-layer chromatography and MALDI-TOF-MS we confirmed changes in the lipid profile, including an altered accumulation of triacylglycerides and an affected ratio of mycolic acids to PDIMs. An Opp loss of function mutant showed no in vitro growth defect, but had diminished burden during chronic infection and produced a slightly delayed time to death of animals when compared to WT Mtb infection.
Flores-Valdez
Mario Alberto
MA
Centro de Investigación y Asistencia en Tecnología y diseño del Estado de Jalisco A.C., Normalistas 800, Colinas de la Normal, 44270 Guadalajara, Jalisco, México. floresv@ciatej.net.mx
Morris
Rowan P
RP
Laval
Françoise
F
Daffé
Mamadou
M
Schoolnik
Gary K
GK
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D014280:Triglycerides; C037230:oligopeptide permease, Bacteria