{"id":26064,"date":"2017-05-06T19:41:05","date_gmt":"2017-05-06T19:41:05","guid":{"rendered":"http:\/\/www.bangalorefirst.in\/?p=26064"},"modified":"2017-05-06T19:48:14","modified_gmt":"2017-05-06T19:48:14","slug":"iit-m-makes-white-light-from-pomegranate-turmeric-extracts","status":"publish","type":"post","link":"https:\/\/www.bangalorefirst.in\/?p=26064","title":{"rendered":"Reversing drug resistance made possible"},"content":{"rendered":"

Drug-resistant E. coli become sensitive to antibiotics when H2S synthesis is inhibited<\/h2>\n
\"Make<\/a>
Make them vulnerable: (From left) Dr. Saurabh Mishra, Dr. Amit Singh, Prashant Shukla and Dr Harinath have been able to reverse antibiotic resistance in E. coli.<\/figcaption><\/figure>\n
\n

Indian researchers have unravelled the mechanism by which hydrogen sulphide (H2S) gas produced by bacteria protects them from antibiotics and plays a key role in helping bacteria develop drug resistance. And by blocking\/disabling the enzyme that triggers the biosynthesis of hydrogen sulphide in bacteria, the researchers from Bengaluru\u2019s Indian Institute of Science (IISc) and Indian Institute of Science Education and Research (IISER) Pune, have been able to reverse antibiotic resistance in E. coli<\/em> bacteria; E. coli <\/em>bacteria were isolated from patients suffering from urinary tract infection. The results were published in the journal Chemical Science.<\/em><\/p>\n

Antibiotics kill by increasing the levels of reactive oxygen species (oxidative stress) inside bacterial cells. So any mechanism that detoxifies or counters reactive oxygen species generated by antibiotics will reduce the efficacy of antibiotics. \u201cHydrogen sulphide does this to nullify the effect of antibiotics,\u201d says Dr. Amit Singh from the Department of Microbiology and Cell Biology at IISc and one of the corresponding authors of the paper. \u201cWhen bacteria face reactive oxygen species a protective mechanism in the bacteria kicks in and more hydrogen sulphide is produced.\u201d Hydrogen sulphide successfully counters reactive oxygen species and reduces the efficacy of antibiotics.<\/p>\n

The researchers carried out simple experiments to establish this. They first ascertained that regardless of the mode of action of antibiotics, the drugs uniformly induce reactive oxygen species formation inside E. coli <\/em>bacteria. Then to test if increased levels of hydrogen sulphide gas inside bacteria counter reactive oxygen species produced upon treatment with antibiotics, a small molecule that produces hydrogen sulphide in a controlled manner inside the bacteria was used. \u201cHydrogen sulphide released by the molecule was able to counter reactive oxygen species and reduce the ability of antibiotics to kill bacteria,\u201d says Dr. Singh.<\/p>\n

The small molecule was synthesised by a team led by Prof. Harinath Chakrapani from the Department of Chemistry, IISER, Pune; he is one of the corresponding authors of the paper. \u201cWe designed the small molecule keeping in mind that synthesis should be easy, efficiency in producing hydrogen sulphide should be high and the molecule should release hydrogen sulphide only inside bacteria and not mammalian cells,\u201d says Vinayak S. Khodade from the Department of Chemistry, IISER, Pune and one of the authors of the paper who contributed equally like the first author. The researchers were able to selectively increase hydrogen sulphide levels inside a wide variety of bacteria.<\/p>\n

To reconfirm hydrogen sulphide\u2019s role in countering reactive oxygen species, the team took multidrug-resistant, pathogenic strains of E. coli <\/em>from patients suffering from urinary tract infection and measured the hydrogen sulphide levels in these strains. \u201cWe found the drug-resistant strains were naturally producing more hydrogen sulphide compared with drug-sensitive E. coli,<\/em>\u201d says Prashant Shukla from the Department of Microbiology and Cell Biology at IISc and the first author of the paper. So the team used a chemical compound that inhibits an enzyme responsible for hydrogen sulphide production. \u201cThere was nearly 50% reduction in drug-resistance when hydrogen sulphide production was blocked,\u201d Dr. Singh says.<\/p>\n

\u201cBacteria that are genetically resistant to antibiotics actually become sensitive to antibiotics when hydrogen sulphide synthesis is inhibited,\u201d says Prof. Chakrapani. The multidrug-resistant E. coli <\/em>regained its ability to survive antibiotics when hydrogen sulphide was once again supplied by introducing the small molecule synthesised by Prof. Chakrapani.<\/p>\n

\u201cAs a result of our study, we have a found new mechanism to develop a new class of drug candidates that specifically target multidrug-resistant bacteria,\u201d says Prof. Chakrapani. The researchers already have a few inhibitors that seem capable of blocking hydrogen sulphide production. But efforts are on to develop a library of inhibitors to increase the chances of success.<\/p>\n

How H2S acts<\/h2>\n

The researchers identified that E. coli <\/em>has two modes of respiration involving two different enzymes. The hydrogen sulphide gas produced shuts down E. coli\u2019s aerobic respiration by targeting the main enzyme (cytochrome bo oxidase (CyoA)) responsible for it. E. coli <\/em>then switches over to an alternative mode of respiration by relying on a different enzyme \u2014 cytochrome bd oxidase (Cydb). Besides enabling respiration, the Cydb enzyme detoxifies the reactive oxygen species produced by antibiotics and blunts the action of antibiotics.<\/p>\n

\u201cSo we found that hydrogen sulphide activates the Cydb enzyme, which, in turn, is responsible for increasing resistance towards antibiotics,\u201d says Dr. Singh. \u201cIf we have a drug-like molecule(s) that blocks hydrogen sulphide production and inhibits Cydb enzyme activity then the combination will be highly lethal against multidrug-resistant bacteria.\u201d<\/p>\n

This combination can also be used along with antibiotics to effectively treat difficult-to-cure bacterial infections.<\/p>\n

The link between hydrogen sulphide and Cydb enzyme in the emergence of drug resistance is another key finding of the study.<\/p>\n

source: http:\/\/www.thehindu.com \/ The Hindu \/ Home> Sci-Tech> Science \/ by R. Prasad \/ May 06th, 2017<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Drug-resistant E. coli become sensitive to antibiotics when H2S synthesis is inhibited Indian researchers have unravelled the mechanism by which hydrogen sulphide (H2S) gas produced by bacteria protects them from antibiotics and plays a key role in helping bacteria develop drug resistance. And by blocking\/disabling the enzyme that triggers the biosynthesis of hydrogen sulphide in … Continue reading Reversing drug resistance made possible<\/span> →<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,15,10],"tags":[],"class_list":["post-26064","post","type-post","status-publish","format-standard","hentry","category-education","category-records-all","category-science-technology"],"jetpack_featured_media_url":"","_links":{"self":[{"href":"https:\/\/www.bangalorefirst.in\/index.php?rest_route=\/wp\/v2\/posts\/26064","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.bangalorefirst.in\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bangalorefirst.in\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bangalorefirst.in\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bangalorefirst.in\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=26064"}],"version-history":[{"count":6,"href":"https:\/\/www.bangalorefirst.in\/index.php?rest_route=\/wp\/v2\/posts\/26064\/revisions"}],"predecessor-version":[{"id":26071,"href":"https:\/\/www.bangalorefirst.in\/index.php?rest_route=\/wp\/v2\/posts\/26064\/revisions\/26071"}],"wp:attachment":[{"href":"https:\/\/www.bangalorefirst.in\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=26064"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bangalorefirst.in\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=26064"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bangalorefirst.in\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=26064"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}