@article{Omollo2023,
abstract = {Tuberculosis (TB) imposes a major burden on global public health which is exacerbated by the escalating number of multidrug-resistant (MDR)-TB cases. There is consequently an urgent need for new anti-TB drugs and combination regimens. We have investigated the natural product antibiotic fusidic acid (FA) for repurposing against Mycobacterium tuberculosis , the causative agent of TB. Here, we report the results of synergy screens combining FA with a panel of approved anti-TB agents. Checkerboard and time-kill kinetics assays identified seven compounds from different chemical classes that synergized with FA in inhibiting the growth of M. tuberculosis in vitro : rifampicin (RIF), a rifamycin and frontline anti-TB drug; the macrolides, erythromycin (ERY), clarithromycin (CLR), and roxythromycin (ROX); the oxazolidinone, linezolid (LZD); the aminoglycoside, streptomycin (STR); and the aminocyclitol, spectinomycin (SPC). Among these, the strongest synergies were observed where FA was combined with SPC and ERY. Moreover, the FA-RIF combination was cidal, while all other FA combinations were bacteriostatic. These results provide in vitro evidence of the potential utility of FA-containing combinations against M. tuberculosis .},
author = {Omollo, Charles and Moosa, Atica and Chibale, Kelly and Warner, Digby F},
doi = {10.1101/2023.01.19.524834},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Omollo et al. - 2023 - Fusidic acid-based drug combinations exhibit enhanced activity against Mycobacterium tuberculosis.pdf:pdf},
journal = {bioRxiv},
keywords = {OA,fund{\_}not{\_}ack,original},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
month = {jan},
pages = {2023.01.19.524834},
publisher = {Cold Spring Harbor Laboratory},
title = {{Fusidic acid-based drug combinations exhibit enhanced activity against \textit{Mycobacterium tuberculosis}}},
url = {https://www.biorxiv.org/content/10.1101/2023.01.19.524834v1 https://www.biorxiv.org/content/10.1101/2023.01.19.524834v1.abstract},
year = {2023}
}

{"_id":"R6ngvJEdtXr99S7SY","bibbaseid":"omollo-moosa-chibale-warner-fusidicacidbaseddrugcombinationsexhibitenhancedactivityagainstimycobacteriumtuberculosisi-2023","author_short":["Omollo, C.","Moosa, A.","Chibale, K.","Warner, D. F"],"bibdata":{"bibtype":"article","type":"article","abstract":"Tuberculosis (TB) imposes a major burden on global public health which is exacerbated by the escalating number of multidrug-resistant (MDR)-TB cases. There is consequently an urgent need for new anti-TB drugs and combination regimens. We have investigated the natural product antibiotic fusidic acid (FA) for repurposing against Mycobacterium tuberculosis , the causative agent of TB. Here, we report the results of synergy screens combining FA with a panel of approved anti-TB agents. Checkerboard and time-kill kinetics assays identified seven compounds from different chemical classes that synergized with FA in inhibiting the growth of M. tuberculosis in vitro : rifampicin (RIF), a rifamycin and frontline anti-TB drug; the macrolides, erythromycin (ERY), clarithromycin (CLR), and roxythromycin (ROX); the oxazolidinone, linezolid (LZD); the aminoglycoside, streptomycin (STR); and the aminocyclitol, spectinomycin (SPC). Among these, the strongest synergies were observed where FA was combined with SPC and ERY. Moreover, the FA-RIF combination was cidal, while all other FA combinations were bacteriostatic. These results provide in vitro evidence of the potential utility of FA-containing combinations against M. tuberculosis .","author":[{"propositions":[],"lastnames":["Omollo"],"firstnames":["Charles"],"suffixes":[]},{"propositions":[],"lastnames":["Moosa"],"firstnames":["Atica"],"suffixes":[]},{"propositions":[],"lastnames":["Chibale"],"firstnames":["Kelly"],"suffixes":[]},{"propositions":[],"lastnames":["Warner"],"firstnames":["Digby","F"],"suffixes":[]}],"doi":"10.1101/2023.01.19.524834","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Omollo et al. - 2023 - Fusidic acid-based drug combinations exhibit enhanced activity against Mycobacterium tuberculosis.pdf:pdf","journal":"bioRxiv","keywords":"OA,fund_not_ack,original","mendeley-tags":"OA,fund_not_ack,original","month":"jan","pages":"2023.01.19.524834","publisher":"Cold Spring Harbor Laboratory","title":"Fusidic acid-based drug combinations exhibit enhanced activity against <i>Mycobacterium tuberculosis</i>","url":"https://www.biorxiv.org/content/10.1101/2023.01.19.524834v1 https://www.biorxiv.org/content/10.1101/2023.01.19.524834v1.abstract","year":"2023","bibtex":"@article{Omollo2023,\r\nabstract = {Tuberculosis (TB) imposes a major burden on global public health which is exacerbated by the escalating number of multidrug-resistant (MDR)-TB cases. There is consequently an urgent need for new anti-TB drugs and combination regimens. We have investigated the natural product antibiotic fusidic acid (FA) for repurposing against Mycobacterium tuberculosis , the causative agent of TB. Here, we report the results of synergy screens combining FA with a panel of approved anti-TB agents. Checkerboard and time-kill kinetics assays identified seven compounds from different chemical classes that synergized with FA in inhibiting the growth of M. tuberculosis in vitro : rifampicin (RIF), a rifamycin and frontline anti-TB drug; the macrolides, erythromycin (ERY), clarithromycin (CLR), and roxythromycin (ROX); the oxazolidinone, linezolid (LZD); the aminoglycoside, streptomycin (STR); and the aminocyclitol, spectinomycin (SPC). Among these, the strongest synergies were observed where FA was combined with SPC and ERY. Moreover, the FA-RIF combination was cidal, while all other FA combinations were bacteriostatic. These results provide in vitro evidence of the potential utility of FA-containing combinations against M. tuberculosis .},\r\nauthor = {Omollo, Charles and Moosa, Atica and Chibale, Kelly and Warner, Digby F},\r\ndoi = {10.1101/2023.01.19.524834},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Omollo et al. - 2023 - Fusidic acid-based drug combinations exhibit enhanced activity against Mycobacterium tuberculosis.pdf:pdf},\r\njournal = {bioRxiv},\r\nkeywords = {OA,fund{\\_}not{\\_}ack,original},\r\nmendeley-tags = {OA,fund{\\_}not{\\_}ack,original},\r\nmonth = {jan},\r\npages = {2023.01.19.524834},\r\npublisher = {Cold Spring Harbor Laboratory},\r\ntitle = {{Fusidic acid-based drug combinations exhibit enhanced activity against \\textit{Mycobacterium tuberculosis}}},\r\nurl = {https://www.biorxiv.org/content/10.1101/2023.01.19.524834v1 https://www.biorxiv.org/content/10.1101/2023.01.19.524834v1.abstract},\r\nyear = {2023}\r\n}\r\n","author_short":["Omollo, C.","Moosa, A.","Chibale, K.","Warner, D. F"],"key":"Omollo2023","id":"Omollo2023","bibbaseid":"omollo-moosa-chibale-warner-fusidicacidbaseddrugcombinationsexhibitenhancedactivityagainstimycobacteriumtuberculosisi-2023","role":"author","urls":{"Paper":"https://www.biorxiv.org/content/10.1101/2023.01.19.524834v1 https://www.biorxiv.org/content/10.1101/2023.01.19.524834v1.abstract"},"keyword":["OA","fund_not_ack","original"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh"],"keywords":["oa","fund_not_ack","original"],"search_terms":["fusidic","acid","based","drug","combinations","exhibit","enhanced","activity","against","mycobacterium","tuberculosis","omollo","moosa","chibale","warner"],"title":"Fusidic acid-based drug combinations exhibit enhanced activity against <i>Mycobacterium tuberculosis</i>","year":2023}