Inflammasome activation dictates the efficacy of antimycobacterial activity of frontline TB drugs

Inflammasome activation dictates the efficacy of antimycobacterial activity of frontline TB drugs | bioRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-M677548'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Inflammasome activation dictates the efficacy of antimycobacterial activity of frontline TB drugs View ORCID Profile Vivek K Rao , View ORCID Profile Anjali Singh , View ORCID Profile Kanika Bisht , Nidhi Yadav , View ORCID Profile Ranjan Nanda doi: https://doi.org/10.1101/2025.04.02.646750 Vivek K Rao 1 CSIR- Institute of Genomics and Integrative Biology; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Vivek K Rao For correspondence: vivek.rao{at}igib.res.in Anjali Singh 2 CSIR- IGIB; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Anjali Singh Kanika Bisht 3 CSIR-IGIB; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kanika Bisht Nidhi Yadav 4 ICGEB, New Delhi Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ranjan Nanda 4 ICGEB, New Delhi Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ranjan Nanda Abstract Info/History Metrics Preview PDF Abstract Recent developments in TB treatment have identified an enormous potential of host targeting entities (host directed therapies-HDT) in achieving better and faster control of infection. We have previously demonstrated the synergistic effect of sertraline with frontline TB drugs in clearing infection in murine tissues. We surmised that understanding the mechanism of sertraline mediated enhancement of antibiotic efficacy would help identify novel pathways of pathogen control. Here, we have used sertraline as a probe to identify host signaling pathways that are important for bacterial control. We identify a role for sertraline mediated modulation of macrophage mitochondrial physiology in this process. We show that the resultant ROS generated in cells acts as the secondary signal for host cell inflammasome activation catalyzing the greater release of IL1beta; and significant efflux of K+ from the SRT treated macrophages. We thus highlight an important relationship between mitochondrial physiology in regulating the activation of the inflammasome to achieve better control of Mtb by infected macrophages. Competing Interest Statement The authors have declared no competing interest. Footnotes A more crisp version of the manuscript has been uploaded Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . View the discussion thread. Back to top Previous Next Posted April 21, 2025. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Share Inflammasome activation dictates the efficacy of antimycobacterial activity of frontline TB drugs Vivek K Rao , Anjali Singh , Kanika Bisht , Nidhi Yadav , Ranjan Nanda bioRxiv 2025.04.02.646750; doi: https://doi.org/10.1101/2025.04.02.646750 Share This Article: Copy Citation Tools Inflammasome activation dictates the efficacy of antimycobacterial activity of frontline TB drugs Vivek K Rao , Anjali Singh , Kanika Bisht , Nidhi Yadav , Ranjan Nanda bioRxiv 2025.04.02.646750; doi: https://doi.org/10.1101/2025.04.02.646750 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Microbiology Subject Areas All Articles Animal Behavior and Cognition (7643) Biochemistry (17717) Bioengineering (13910) Bioinformatics (42015) Biophysics (21477) Cancer Biology (18626) Cell Biology (25536) Clinical Trials (138) Developmental Biology (13392) Ecology (19935) Epidemiology (2067) Evolutionary Biology (24356) Genetics (15617) Genomics (22530) Immunology (17755) Microbiology (40437) Molecular Biology (17200) Neuroscience (88703) Paleontology (667) Pathology (2840) Pharmacology and Toxicology (4832) Physiology (7657) Plant Biology (15171) Scientific Communication and Education (2046) Synthetic Biology (4304) Systems Biology (9828) Zoology (2272)