ArticleScientific reports2026
Genetic interference of distinctive Mycobacterium tuberculosis peptidoglycan modifications enhances β-lactam susceptibility and reveals expression-sensitive host immune dynamics.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The high mortality associated with tuberculosis (TB), alongside the lack of efficient therapeutics against emerging multidrug-resistant Mycobacterium tuberculosis (Mtb) strains, emphasizes the need for novel antitubercular targets. Mycobacterial peptidoglycan (PG), displaying characteristic modifications comprising the amidation of D-iso-glutamate (D-iGlu) and the N-glycolylation of muramic acid, is therefore a promising therapeutic target. The genes encoding the enzymes mediating these modifications (murT/gatD and namH) were silenced in Mtb using CRISPR interference (CRISPRi) to investigate their impact on β-lactam susceptibility and host immune responses. First, qRT-PCR confirmed successful target mRNA knockdown and phenotyping assays corroborated the essentiality of D-iGlu amidation for mycobacterial growth, in contrast to muramic acid N-glycolylation. The susceptibility assays demonstrated that both PG modifications promote β-lactam resistance. Indeed, we observed reductions in the minimum fractional inhibitory concentration index (FICI
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