7 documents found, page 1 of 1

Effects of CwlM, a peptidoglycan synthesis regulator, on beta-lactam tolerance ...

Background: The emergence and spread of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (Mtb) urge the development of novel drugs and efficient therapeutic programs. A recent study aiming to uncover differential beta-lactam susceptibility phenotypes in clinical strains of Mtb found that the M237V substitution in cwlM (Rv3915) was associated with increased susceptibility to amoxicillin. Consideri...

Ethambutol and meropenem/clavulanate synergy promotes enhanced extracellular an...

Increasing evidence supports the repositioning of beta-lactams for tuberculosis (TB) therapy, but further research on their interaction with conventional anti-TB agents is still warranted. Moreover, the complex cell envelope of Mycobacterium tuberculosis (Mtb) may pose an additional obstacle to beta-lactam diffusion. In this context, we aimed to identify synergies between beta-lactams and anti-TB drugs ethambut...

Deciphering unexploited features of drug-repurposing beta-lactams against tuber...

Tuberculosis (TB) still figures as one of the leading death causes by a single infectious agent worldwide. The natural capacity of Mycobacterium tuberculosis (Mtb) to evade and subvert host immune responses, coupled with the increasing threat of drug-resistant TB (DR-TB), contribute to the difficult containment of this infection. Alternative treatment options for DR-TB are desperately required, either by identi...

CRISPRi-mediated characterization of novel anti-tuberculosis targets: mycobacte...

The lack of effective therapeutics against emerging multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) prompts the identification of novel anti-tuberculosis targets. The essential nature of the peptidoglycan (PG) layer of the mycobacterial cell wall, which features several distinctive modifications, such as the N-glycolylation of muramic acid and the amidation of D-iso-glutamate, makes it a target...

Uncovering Beta-Lactam Susceptibility Patterns in Clinical Isolates of Mycobact...

The increasing threat of drug resistance and a stagnated pipeline of novel therapeutics endanger the eradication of tuberculosis. Beta-lactams constitute promising additions to the current therapeutic arsenal and two carbapenems are included in group C of medicines recommended by the WHO for use in longer multidrug-resistant tuberculosis regimens. However, the determinants underlining diverse Mycobacterium tube...

Identification of drivers of mycobacterial resistance to peptidoglycan synthesi...

Beta-lactams have been excluded from tuberculosis therapy due to the intrinsic resistance of Mycobacterium tuberculosis (Mtb) to this antibiotic class, usually attributed to a potent beta-lactamase, BlaC, and to an unusually complex cell wall. In this pathogen, the peptidoglycan is cross-linked by penicillin-binding proteins (PBPs) and L,D-transpeptidases, the latter resistant to inhibition by most beta-lactams...

WGS-based dual strategy for the identification of key targets to enhance beta-l...