{"id":197313,"date":"2021-03-09T00:37:48","date_gmt":"2021-03-08T21:37:48","guid":{"rendered":"https:\/\/en.buradabiliyorum.com\/research-pinpoints-unique-drug-target-in-antibiotic-resistant-bacteria\/"},"modified":"2021-03-09T00:37:48","modified_gmt":"2021-03-08T21:37:48","slug":"research-pinpoints-unique-drug-target-in-antibiotic-resistant-bacteria","status":"publish","type":"post","link":"https:\/\/buradabiliyorum.com\/en\/research-pinpoints-unique-drug-target-in-antibiotic-resistant-bacteria\/","title":{"rendered":"#Research pinpoints unique drug target in antibiotic resistant bacteria"},"content":{"rendered":"

“#Research pinpoints unique drug target in antibiotic resistant bacteria<\/strong>”<\/p>\n

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\"Research
\n New ideas urgently needed for antibiotic development. Credit: Shutterstock
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Researchers have identified a critical mechanism that allows deadly bacteria to gain resistance to antibiotics.<\/p>\n


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The findings offer a potential new drug target in the search for effective new antibiotics as we face the growing threat of antimicrobial resistance (AMR) and infections caused by bacterial pathogens.<\/p>\n

The study investigated quinolone antibiotics which are used to treat a range of bacterial infections, including TB (tuberculosis). Quinolones work by inhibiting bacterial enzymes, gyrase and topoisomerase IV, thereby preventing DNA replication and RNA synthesis essential to growth.<\/p>\n

They are highly-successful antimicrobial agents widely used in current medicine, however bacterial resistance to them and other treatments is a serious problem.<\/p>\n

Previous studies had identified one resistance mechanism caused by the production of pentapeptide repeat proteins (PRPs), a family of molecules that also act as DNA gyrase inhibitors.<\/p>\n

One of these, called MfpA, confers quinolone resistance to Mycobacterium tuberculosis, the causative agent of TB.<\/p>\n

In this study John Innes Centre researchers in the group of Professor Tony Maxwell set out to discover how PRPs such as MfpA, work at the molecular level.<\/p>\n

They purified MfpA from Mycobacterium smegmatis, a close relative of M. tuberculosis, and showed that it can inhibit the supercoiling reaction of DNA gyrase, the target of quinolones in TB causing mycobacteria.<\/p>\n

Further investigations showed that MfpA can prevent poisoning of gyrase by quinolones, thus protecting the bacterial host cell from the antibiotic.<\/p>\n

Using X-ray crystallography, the researchers showed that MfpA binds to the ATPase domain of gyrase, and that this explains its ability to both inhibit the supercoiling reaction and prevent quinolone poisoning.<\/p>\n

“We did not expect the exact mechanism of MfpA to be the prevention of DNA binding to the gyrase ATPase domain; this is a unique mode of action,” said Professor Tony Maxwell, corresponding author of the study.<\/p>\n

“We believe this understanding will help drive new ideas for antibiotic development among academics and researchers in the pharma industry,” he added.<\/p>\n

Further investigative work will involve molecular modelling based on the MfpA-gyrase structure to design small molecules that could mimic this interaction and offer more insights into how it works.<\/p>\n

The study “Pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic” app<\/a>ears in PNAS<\/i>.<\/p>\n\n

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Scientists explore the action mechanism of a new antibiotic\n <\/p><\/div>\n

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\n More information:<\/strong>
\n Lipeng Feng el al., “The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic,” PNAS<\/i> (2021). www.pnas.org\/cgi\/doi\/10.1073\/pnas.2016705118<\/a><\/p><\/div>\n
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Citation<\/strong>:
\n Research pinpoints unique drug target in antibiotic resistant bacteria (2021, March 8)
\n retrieved 8 March 2021
\n from https:\/\/phys.org\/news<\/a>\/2021-03-unique-drug-antibiotic-resistant-bacteria.html<\/p>\n

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\n part may be reproduced without the written permission. The content is provided for information purposes only.<\/p><\/div>\n<\/p><\/div>\n