A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 176

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML

File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Inhibition of MptpB phosphatase from Mycobacterium tuberculosis impairs mycobacterial survival in macrophages. | LitMetric

AI Article Synopsis

  • The study focuses on identifying selective inhibitors for the MptpB protein in Mycobacterium tuberculosis, which helps the bacteria survive inside host macrophages.
  • Researchers tested various compounds to see which ones effectively inhibited MptpB and evaluated their impact on infected macrophages.
  • They discovered a new class of isoxazole-based compounds that significantly reduce mycobacterial growth without killing the bacteria, indicating a potential new treatment strategy for tuberculosis that leverages MptpB inhibition.

Article Abstract

Objectives: The secreted Mycobacterium tuberculosis protein tyrosine phosphatase (MptpB) is a virulence factor for M. tuberculosis and contributes to its survival within host macrophages. The aim of this study was to identify potent selective inhibitors of MptpB and to determine the efficacy of these compounds in mycobacterium-infected macrophages.

Methods: The inhibitory effect of a small library of compounds on MptpB was first examined in vitro. The efficacy of these compounds was further examined in mycobacterium-infected macrophages.

Results: We have identified a new family of double-site isoxazole-based compounds that are potent selective inhibitors of MptpB. Importantly, the inhibitors substantially reduce mycobacterial survival in infected macrophages. In contrast with current anti-tubercular drugs, these MptpB inhibitors do not have bactericidal action but rather, severely impair mycobacterial growth within macrophages. Docking analysis suggests a double-site binding mechanism of inhibition with the isoxazole head in the active site and a salicylate group in a secondary binding pocket that is a unique structural feature of MptpB.

Conclusions: These results provide the first evidence that inhibition of phosphatases can be exploited against mycobacterial infections. The cell activity of the inhibitors together with the lack of MptpB human orthologues suggests a strong potential for these compounds to be developed as drug candidates against tuberculosis and promises a new therapeutic strategy to tackle clearance and reduce the persistence of M. tuberculosis infection.

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkp031DOI Listing

Publication Analysis

Top Keywords

mycobacterium tuberculosis
8
mycobacterial survival
8
potent selective
8
selective inhibitors
8
inhibitors mptpb
8
efficacy compounds
8
mptpb
6
tuberculosis
5
inhibitors
5
compounds
5

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!