Down-regulation of <i>N</i>
-acetylglucosamine-1-phosphate transferase (WecA) enhanced the sensitivity of <i>Mycobacterium smegmatis</i>
 against rifampin

Xu, Liming; Lei, Qian; Kang, Jian; ShA, Shukurov; Xin, Yi; Lu, Shuo; Ma, Yufang

doi:10.1111/jam.13228

Cited by 3 publications

(3 citation statements)

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“…The enzyme N -acetylglucosamine-1-phosphate transferase, GlcNAc-1-P transferase (WecA), catalyses the first step of this linker biosynthesis. For this reason, WecA inhibitors, such as CPZEN-45 ( Figure 2 C), a caprazamycin derivative, prevent the growth of Mtb [ 53 , 54 ].…”

Section: Emerging Mtb Drug Targetsmentioning

confidence: 99%

Target Identification in Anti-Tuberculosis Drug Discovery

Capela

Félix

Clariano

et al. 2023

IJMS

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Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis (TB), a disease that, although preventable and curable, remains a global epidemic due to the emergence of resistance and a latent form responsible for a long period of treatment. Drug discovery in TB is a challenging task due to the heterogeneity of the disease, the emergence of resistance, and uncomplete knowledge of the pathophysiology of the disease. The limited permeability of the cell wall and the presence of multiple efflux pumps remain a major barrier to achieve effective intracellular drug accumulation. While the complete genome sequence of Mtb has been determined and several potential protein targets have been validated, the lack of adequate models for in vitro and in vivo studies is a limiting factor in TB drug discovery programs. In current therapeutic regimens, less than 0.5% of bacterial proteins are targeted during the biosynthesis of the cell wall and the energetic metabolism of two of the most important processes exploited for TB chemotherapeutics. This review provides an overview on the current challenges in TB drug discovery and emerging Mtb druggable proteins, and explains how chemical probes for protein profiling enabled the identification of new targets and biomarkers, paving the way to disruptive therapeutic regimens and diagnostic tools.

show abstract

Section: Emerging Mtb Drug Targetsmentioning

confidence: 99%

Target Identification in Anti-Tuberculosis Drug Discovery

Capela

Félix

Clariano

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…The enzyme N-acetylglucosamine-1phosphate transferase, GlcNAc-1-P transferase (WecA) catalyses the first step of this linker biosynthesis. For this reason, WecA inhibitors such CPZEN-45 (Figure 2C), a caprazamycin derivative, prevents the growth of Mtb [53,54].…”

Section: Cell Wallmentioning

confidence: 99%

Target Identification in Anti-tuberculosis Drug Discovery

Capela¹,

Félix²,

Clariano³

et al. 2023

Preprint

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Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis (TB), a disease that alt-hough preventable and curable, remains a global epidemic due to the emergence of resistance and a latent form responsible for a long period of treatment. Drug discovery in TB is a challenging task due to the heterogeneity of the disease, the emergence of resistance and an uncomplete knowledge of the pathophysiology of the disease. The limited permeability of the cell wall and the presence of multiple efflux pumps remain a major barrier to achieve effective intracellular drug accumulation. While the complete genome sequence of Mtb has been determined and several potential protein targets have been validated, the lack of adequate models for in vitro and in vivo studies is a limit-ing factor in TB drug discovery programs. In current therapeutic regimens, less than 0.5% of bac-terial proteins are targeted being the biosynthesis of the cell wall and the energetic metabolism two of the most important processes exploited for TB chemotherapeutics. This review provides an overview on the current challenges in TB drug discovery and emerging Mtb druggable proteins, and how chemical probes for protein profiling enabled the identification of new targets and bi-omarkers, paving the way to disruptive therapeutic regimens and diagnostic tools.

show abstract

“…Recently, Xu et al. 78 have found that downregulation of WecA can enhance the sensitivity of MTB to first-line rifampin. Thus, with the development of inhibitors of WecA, a new combination treatment for TB may be established.…”

Section: Tuberculosis Cell Wall: Drug Targets and Therapeuti...mentioning

confidence: 99%