"On demand" redox buffering by H2S contributes to antibiotic resistance revealed by a bacteria-specific H2S donor
Understanding the mechanisms of antimicrobial resistance (AMR) will help launch a counter-offensive against human pathogens that threaten our ability to effectively treat common infections. Herein, we report bis(4-nitrobenzyl)sulfanes, which are activated by a bacterial enzyme to produce hydrogen su...
Gespeichert in:
| Veröffentlicht in: | Chemical science (Cambridge) 2017-07, Vol.8 (7), p.4967-4972 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4972 |
|---|---|
| container_issue | 7 |
| container_start_page | 4967 |
| container_title | Chemical science (Cambridge) |
| container_volume | 8 |
| creator | Shukla, Prashant Khodade, Vinayak S SharathChandra, Mallojjala Chauhan, Preeti Mishra, Saurabh Siddaramappa, Shivakumara Pradeep, Bulagonda Eswarappa Singh, Amit Chakrapani, Harinath |
| description | Understanding the mechanisms of antimicrobial resistance (AMR) will help launch a counter-offensive against human pathogens that threaten our ability to effectively treat common infections. Herein, we report bis(4-nitrobenzyl)sulfanes, which are activated by a bacterial enzyme to produce hydrogen sulfide (H2S) gas. We found that H2S helps maintain redox homeostasis and protects bacteria against antibiotic-triggered oxidative stress "on demand", through activation of alternate respiratory oxidases and cellular antioxidants. We discovered, a hitherto unknown role for this gas, that chemical inhibition of H2S biosynthesis reversed antibiotic resistance in multidrug-resistant (MDR) uropathogenic Escherichia coli strains of clinical origin, whereas exposure to the H2S donor restored drug tolerance. Together, our study provides a greater insight into the dynamic defence mechanisms of this gas, modes of antibiotic action as well as resistance while progressing towards new pharmacological targets to address AMR. |
| doi_str_mv | 10.1039/c7sc00873b |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1945221407</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1945221407</sourcerecordid><originalsourceid>FETCH-LOGICAL-j411t-ba13f0d944d32c5c136ad76195225ad905e72575fd0b7f2c50f13a62a51625453</originalsourceid><addsrcrecordid>eNqNkctKBDEQRYMoKjobvyC4ctOaZ6ezEUR8geBCXTeVR2ukJxk7aXH-3gyK4M7a1IW691BFIXREySklXJ9ZlS0hneJmC-0zImjTSq63fzUje2iR8xupxTmVTO2iPdZpqQUj--j9-CFi55cQ3TGevEuf2MzD4KcQX7BZ41v2iG2KZQpmLj7jkjDEEkxIJdgayCEXiNZX-eFh9G4TAmzAlsqAJq-8DUO1bkAuxTQdop0BxuwXP_0APV9fPV3eNvcPN3eXF_fNm6C0NAYoH4jTQjjOrLSUt-BUS7VkTILTRHrFpJKDI0YN1UEGyqFlIGnLpJD8AJ1_c1ezWXpnfT0Cxn41hSVM6z5B6P9OYnjtX9JHL1uiOtlWwMkPYErvs8-lX4Zs_ThC9GnOPdWi7kIFUf-wMtl1jLT0H1aqdf2gUPwLngOR5g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1919953947</pqid></control><display><type>article</type><title>"On demand" redox buffering by H2S contributes to antibiotic resistance revealed by a bacteria-specific H2S donor</title><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>PubMed Central</source><creator>Shukla, Prashant ; Khodade, Vinayak S ; SharathChandra, Mallojjala ; Chauhan, Preeti ; Mishra, Saurabh ; Siddaramappa, Shivakumara ; Pradeep, Bulagonda Eswarappa ; Singh, Amit ; Chakrapani, Harinath</creator><creatorcontrib>Shukla, Prashant ; Khodade, Vinayak S ; SharathChandra, Mallojjala ; Chauhan, Preeti ; Mishra, Saurabh ; Siddaramappa, Shivakumara ; Pradeep, Bulagonda Eswarappa ; Singh, Amit ; Chakrapani, Harinath</creatorcontrib><description>Understanding the mechanisms of antimicrobial resistance (AMR) will help launch a counter-offensive against human pathogens that threaten our ability to effectively treat common infections. Herein, we report bis(4-nitrobenzyl)sulfanes, which are activated by a bacterial enzyme to produce hydrogen sulfide (H2S) gas. We found that H2S helps maintain redox homeostasis and protects bacteria against antibiotic-triggered oxidative stress "on demand", through activation of alternate respiratory oxidases and cellular antioxidants. We discovered, a hitherto unknown role for this gas, that chemical inhibition of H2S biosynthesis reversed antibiotic resistance in multidrug-resistant (MDR) uropathogenic Escherichia coli strains of clinical origin, whereas exposure to the H2S donor restored drug tolerance. Together, our study provides a greater insight into the dynamic defence mechanisms of this gas, modes of antibiotic action as well as resistance while progressing towards new pharmacological targets to address AMR.</description><identifier>ISSN: 2041-6520</identifier><identifier>EISSN: 2041-6539</identifier><identifier>DOI: 10.1039/c7sc00873b</identifier><identifier>PMID: 28959420</identifier><language>eng</language><publisher>Royal Society of Chemistry</publisher><subject>Activation ; Antibiotics ; Bacteria ; Chemistry ; Demand ; Drugs ; Enzymes ; Escherichia coli ; Launches ; Psychological effects</subject><ispartof>Chemical science (Cambridge), 2017-07, Vol.8 (7), p.4967-4972</ispartof><rights>This journal is © The Royal Society of Chemistry 2017 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607856/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607856/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Shukla, Prashant</creatorcontrib><creatorcontrib>Khodade, Vinayak S</creatorcontrib><creatorcontrib>SharathChandra, Mallojjala</creatorcontrib><creatorcontrib>Chauhan, Preeti</creatorcontrib><creatorcontrib>Mishra, Saurabh</creatorcontrib><creatorcontrib>Siddaramappa, Shivakumara</creatorcontrib><creatorcontrib>Pradeep, Bulagonda Eswarappa</creatorcontrib><creatorcontrib>Singh, Amit</creatorcontrib><creatorcontrib>Chakrapani, Harinath</creatorcontrib><title>"On demand" redox buffering by H2S contributes to antibiotic resistance revealed by a bacteria-specific H2S donor</title><title>Chemical science (Cambridge)</title><description>Understanding the mechanisms of antimicrobial resistance (AMR) will help launch a counter-offensive against human pathogens that threaten our ability to effectively treat common infections. Herein, we report bis(4-nitrobenzyl)sulfanes, which are activated by a bacterial enzyme to produce hydrogen sulfide (H2S) gas. We found that H2S helps maintain redox homeostasis and protects bacteria against antibiotic-triggered oxidative stress "on demand", through activation of alternate respiratory oxidases and cellular antioxidants. We discovered, a hitherto unknown role for this gas, that chemical inhibition of H2S biosynthesis reversed antibiotic resistance in multidrug-resistant (MDR) uropathogenic Escherichia coli strains of clinical origin, whereas exposure to the H2S donor restored drug tolerance. Together, our study provides a greater insight into the dynamic defence mechanisms of this gas, modes of antibiotic action as well as resistance while progressing towards new pharmacological targets to address AMR.</description><subject>Activation</subject><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Chemistry</subject><subject>Demand</subject><subject>Drugs</subject><subject>Enzymes</subject><subject>Escherichia coli</subject><subject>Launches</subject><subject>Psychological effects</subject><issn>2041-6520</issn><issn>2041-6539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqNkctKBDEQRYMoKjobvyC4ctOaZ6ezEUR8geBCXTeVR2ukJxk7aXH-3gyK4M7a1IW691BFIXREySklXJ9ZlS0hneJmC-0zImjTSq63fzUje2iR8xupxTmVTO2iPdZpqQUj--j9-CFi55cQ3TGevEuf2MzD4KcQX7BZ41v2iG2KZQpmLj7jkjDEEkxIJdgayCEXiNZX-eFh9G4TAmzAlsqAJq-8DUO1bkAuxTQdop0BxuwXP_0APV9fPV3eNvcPN3eXF_fNm6C0NAYoH4jTQjjOrLSUt-BUS7VkTILTRHrFpJKDI0YN1UEGyqFlIGnLpJD8AJ1_c1ezWXpnfT0Cxn41hSVM6z5B6P9OYnjtX9JHL1uiOtlWwMkPYErvs8-lX4Zs_ThC9GnOPdWi7kIFUf-wMtl1jLT0H1aqdf2gUPwLngOR5g</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Shukla, Prashant</creator><creator>Khodade, Vinayak S</creator><creator>SharathChandra, Mallojjala</creator><creator>Chauhan, Preeti</creator><creator>Mishra, Saurabh</creator><creator>Siddaramappa, Shivakumara</creator><creator>Pradeep, Bulagonda Eswarappa</creator><creator>Singh, Amit</creator><creator>Chakrapani, Harinath</creator><general>Royal Society of Chemistry</general><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>8BQ</scope><scope>JG9</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170701</creationdate><title>"On demand" redox buffering by H2S contributes to antibiotic resistance revealed by a bacteria-specific H2S donor</title><author>Shukla, Prashant ; Khodade, Vinayak S ; SharathChandra, Mallojjala ; Chauhan, Preeti ; Mishra, Saurabh ; Siddaramappa, Shivakumara ; Pradeep, Bulagonda Eswarappa ; Singh, Amit ; Chakrapani, Harinath</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j411t-ba13f0d944d32c5c136ad76195225ad905e72575fd0b7f2c50f13a62a51625453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Activation</topic><topic>Antibiotics</topic><topic>Bacteria</topic><topic>Chemistry</topic><topic>Demand</topic><topic>Drugs</topic><topic>Enzymes</topic><topic>Escherichia coli</topic><topic>Launches</topic><topic>Psychological effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shukla, Prashant</creatorcontrib><creatorcontrib>Khodade, Vinayak S</creatorcontrib><creatorcontrib>SharathChandra, Mallojjala</creatorcontrib><creatorcontrib>Chauhan, Preeti</creatorcontrib><creatorcontrib>Mishra, Saurabh</creatorcontrib><creatorcontrib>Siddaramappa, Shivakumara</creatorcontrib><creatorcontrib>Pradeep, Bulagonda Eswarappa</creatorcontrib><creatorcontrib>Singh, Amit</creatorcontrib><creatorcontrib>Chakrapani, Harinath</creatorcontrib><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemical science (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shukla, Prashant</au><au>Khodade, Vinayak S</au><au>SharathChandra, Mallojjala</au><au>Chauhan, Preeti</au><au>Mishra, Saurabh</au><au>Siddaramappa, Shivakumara</au><au>Pradeep, Bulagonda Eswarappa</au><au>Singh, Amit</au><au>Chakrapani, Harinath</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>"On demand" redox buffering by H2S contributes to antibiotic resistance revealed by a bacteria-specific H2S donor</atitle><jtitle>Chemical science (Cambridge)</jtitle><date>2017-07-01</date><risdate>2017</risdate><volume>8</volume><issue>7</issue><spage>4967</spage><epage>4972</epage><pages>4967-4972</pages><issn>2041-6520</issn><eissn>2041-6539</eissn><abstract>Understanding the mechanisms of antimicrobial resistance (AMR) will help launch a counter-offensive against human pathogens that threaten our ability to effectively treat common infections. Herein, we report bis(4-nitrobenzyl)sulfanes, which are activated by a bacterial enzyme to produce hydrogen sulfide (H2S) gas. We found that H2S helps maintain redox homeostasis and protects bacteria against antibiotic-triggered oxidative stress "on demand", through activation of alternate respiratory oxidases and cellular antioxidants. We discovered, a hitherto unknown role for this gas, that chemical inhibition of H2S biosynthesis reversed antibiotic resistance in multidrug-resistant (MDR) uropathogenic Escherichia coli strains of clinical origin, whereas exposure to the H2S donor restored drug tolerance. Together, our study provides a greater insight into the dynamic defence mechanisms of this gas, modes of antibiotic action as well as resistance while progressing towards new pharmacological targets to address AMR.</abstract><pub>Royal Society of Chemistry</pub><pmid>28959420</pmid><doi>10.1039/c7sc00873b</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-6520 |
| ispartof | Chemical science (Cambridge), 2017-07, Vol.8 (7), p.4967-4972 |
| issn | 2041-6520 2041-6539 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1945221407 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central |
| subjects | Activation Antibiotics Bacteria Chemistry Demand Drugs Enzymes Escherichia coli Launches Psychological effects |
| title | "On demand" redox buffering by H2S contributes to antibiotic resistance revealed by a bacteria-specific H2S donor |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T05%3A48%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=%22On%20demand%22%20redox%20buffering%20by%20H2S%20contributes%20to%20antibiotic%20resistance%20revealed%20by%20a%20bacteria-specific%20H2S%20donor&rft.jtitle=Chemical%20science%20(Cambridge)&rft.au=Shukla,%20Prashant&rft.date=2017-07-01&rft.volume=8&rft.issue=7&rft.spage=4967&rft.epage=4972&rft.pages=4967-4972&rft.issn=2041-6520&rft.eissn=2041-6539&rft_id=info:doi/10.1039/c7sc00873b&rft_dat=%3Cproquest_pubme%3E1945221407%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1919953947&rft_id=info:pmid/28959420&rfr_iscdi=true |