{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T21:45:55Z","timestamp":1757540755722,"version":"3.37.3"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R56 AI118361","R01 AI063200","K24 065298","K08 AI106420)"],"award-info":[{"award-number":["R56 AI118361","R01 AI063200","K24 065298","K08 AI106420)"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,16]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n We evaluated the relationship between response to efflux pump inhibition in fluoroquinolone-resistant Mycobacterium tuberculosis (Mtb) isolates and differences in gene expression and expression quantitative trait loci (eQTL).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We determined ofloxacin minimum inhibitory concentration (MIC) for ofloxacin-resistant and -susceptible Mtb isolates without and with the efflux pump inhibitor verapamil. We performed RNA sequencing (RNA-seq), whole genome sequencing (WGS), and eQTL analysis, focusing on efflux pump, transport, and secretion-associated genes.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Of 42 ofloxacin-resistant Mtb isolates, 27 had adequate WGS coverage and acceptable RNA-seq quality. Of these 27, 7 had &gt;2-fold reduction in ofloxacin MIC with verapamil; 6 had 2-fold reduction, and 14 had &lt;2-fold reduction. Five genes (including Rv0191) had significantly increased expression in the MIC fold change &gt;2 compared to &lt;2 groups. Among regulated genes, 31 eQTLs (without ofloxacin) and 35 eQTLs (with ofloxacin) had significant allele frequency differences between MIC fold change &gt;2 and &lt;2 groups. Of these, Rv1410c, Rv2459, and Rv3756c (without ofloxacin) and Rv0191 and Rv3756c (with ofloxacin) have previously been associated with antituberculosis drug resistance.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In this first reported eQTL analysis in Mtb, Rv0191 had increased gene expression and significance in eQTL analysis, making it a candidate for functional evaluation of efflux-mediated fluoroquinolone resistance in Mtb.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/infdis\/jiad112","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T16:01:00Z","timestamp":1682006460000},"page":"469-478","source":"Crossref","is-referenced-by-count":4,"title":["Mycobacterium tuberculosis<\/i> Gene Expression Associated With Fluoroquinolone Resistance and Efflux Pump Inhibition"],"prefix":"10.1093","volume":"228","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7631-9796","authenticated-orcid":false,"given":"Yuri F","family":"van der 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