Mycobacterium Tuberculosis Modulates Its Cell Surface Via an Oligopeptide Permease (Opp) Transport System
Overview
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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.
Campos D, Canales C, Demarqui F, Fernandes G, Dos Santos C, Prates J Front Microbiol. 2024; 15:1487829.
PMID: 39464394 PMC: 11502347. DOI: 10.3389/fmicb.2024.1487829.
Molecular basis for substrate transport of ABC importer DppABCD.
Hu T, Yang X, Zhu Y, Liu F, Yang X, Xiong Z Sci Adv. 2024; 10(12):eadk8521.
PMID: 38507491 PMC: 10954201. DOI: 10.1126/sciadv.adk8521.
Li Q, Peng Z, Fu X, Wang H, Zhao Z, Pang Y BMC Infect Dis. 2022; 22(1):256.
PMID: 35287590 PMC: 8919692. DOI: 10.1186/s12879-021-06967-y.
Fernando D, Gee C, Griffith E, Meyer C, Wilt L, Tangallapally R Tuberculosis (Edinb). 2021; 132:102157.
PMID: 34894561 PMC: 8818035. DOI: 10.1016/j.tube.2021.102157.
Physicochemical properties and transporters: keys to efficacious antitubercular drugs?.
Fullam E, Young R RSC Med Chem. 2021; 12(1):43-56.
PMID: 34041481 PMC: 8130550. DOI: 10.1039/d0md00265h.