000147794 001__ 147794
000147794 005__ 20251113074339.0
000147794 0247_ $$2doi$$a10.1093/jambio/lxae286
000147794 0248_ $$2sideral$$a141335
000147794 037__ $$aART-2024-141335
000147794 041__ $$aeng
000147794 100__ $$aDe Boeck, Nathan
000147794 245__ $$aA single upstream mutation of <i>whiB7</i> underlies amikacin and clarithromycin resistance in <i>Mycobacterium abscessus</i>
000147794 260__ $$c2024
000147794 5060_ $$aAccess copy available to the general public$$fUnrestricted
000147794 5203_ $$aAims: We aimed to investigate the molecular mechanisms underlying the survival of Mycobacterium abscessus when faced with antibiotic combination therapy. By conducting evolution experiments and whole-genome sequencing (WGS), we sought to identify genetic variants associated with stress response mechanisms, with a particular focus on drug survival and resistance. Methods and results: We conducted evolution experiments on M. abscessus, exposing the bacteria to a combination therapy of amikacin and rifabutin. Genetic mutations associated with increased antibiotic survival and altered susceptibility were subsequently identified by WGS. We focused on mutations that contribute to stress response mechanisms and tolerance. Of particular interest was a novel frameshift mutation in MAB_3509c, a gene of unknown function within the upstream open reading frame of whiB7. A MAB_3509c knockout mutant was constructed, and expression of downstream drug resistance genes was assessed by RT-qPCR. Mutation of MAB_3509c results in increased RNA levels of whiB7 and downstream stress response genes such as eis2, which is responsible for aminoglycoside resistance. Conclusion: Our findings demonstrate the importance of whiB7 in the adaptive stress response in M. abscessus. Moreover, our results highlight the complexity of M. abscessus adapting to drug stress and underscore the need for further research.
000147794 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/AEI/PRE2020-096507$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-104690RB-I00
000147794 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000147794 590__ $$a3.2$$b2024
000147794 592__ $$a0.779$$b2024
000147794 591__ $$aMICROBIOLOGY$$b76 / 163 = 0.466$$c2024$$dQ2$$eT2
000147794 593__ $$aApplied Microbiology and Biotechnology$$c2024$$dQ2
000147794 591__ $$aBIOTECHNOLOGY & APPLIED MICROBIOLOGY$$b75 / 177 = 0.424$$c2024$$dQ2$$eT2
000147794 593__ $$aMedicine (miscellaneous)$$c2024$$dQ2
000147794 593__ $$aBiotechnology$$c2024$$dQ2
000147794 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000147794 700__ $$aVillellas, Cristina$$uUniversidad de Zaragoza
000147794 700__ $$aCrespo-Yuste, Estefanía$$uUniversidad de Zaragoza
000147794 700__ $$0(orcid)0000-0001-8841-6593$$aGonzalo-Asensio, Jesús$$uUniversidad de Zaragoza
000147794 700__ $$aBuckley, Peter T
000147794 700__ $$aThys, Kim
000147794 700__ $$aVuong, Cuong
000147794 700__ $$aLounis, Nacer
000147794 700__ $$aVerstraeten, Natalie
000147794 700__ $$aMichiels, Jan
000147794 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000147794 773__ $$g135, 11 (2024), lxae286 [13 pp.]$$pJ. appl. microbiol.$$tJournal of Applied Microbiology$$x1364-5072
000147794 8564_ $$s811923$$uhttps://zaguan.unizar.es/record/147794/files/texto_completo.pdf$$yPostprint$$zinfo:eu-repo/date/embargoEnd/2025-11-13
000147794 8564_ $$s2290609$$uhttps://zaguan.unizar.es/record/147794/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint$$zinfo:eu-repo/date/embargoEnd/2025-11-13
000147794 909CO $$ooai:zaguan.unizar.es:147794$$particulos$$pdriver
000147794 951__ $$a2025-09-22-14:51:48
000147794 980__ $$aARTICLE