Resistance to pentamidine is mediated by AdeAB, regulated by AdeRS, and influenced by growth conditions in Acinetobacter baumannii ATCC 17978

dc.contributor.author Adams, Felise G
dc.contributor.author Stroeher, Uwe Horst
dc.contributor.author Hassan, Karl Adam
dc.contributor.author Marri, Shashikanth
dc.contributor.author Brown, Melissa Hackett
dc.date.accessioned 2018-10-04T04:27:05Z
dc.date.available 2018-10-04T04:27:05Z
dc.date.issued 2018-05-11
dc.description This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_US
dc.description.abstract In recent years, effective treatment of infections caused by Acinetobacter baumannii has become challenging due to the ability of the bacterium to acquire or up-regulate antimicrobial resistance determinants. Two component signal transduction systems are known to regulate expression of virulence factors including multidrug efflux pumps. Here, we investigated the role of the AdeRS two component signal transduction system in regulating the AdeAB efflux system, determined whether AdeA and/or AdeB can individually confer antimicrobial resistance, and explored the interplay between pentamidine resistance and growth conditions in A. baumannii ATCC 17978. Results identified that deletion of adeRS affected resistance towards chlorhexidine and 4’,6-diamidino-2-phenylindole dihydrochloride, two previously defined AdeABC substrates, and also identified an 8-fold decrease in resistance to pentamidine. Examination of ΔadeA, ΔadeB and ΔadeAB cells augmented results seen for ΔadeRS and identified a set of dicationic AdeAB substrates. RNA-sequencing of ΔadeRS revealed transcription of 290 genes were ≥2-fold altered compared to the wildtype. Pentamidine shock significantly increased adeA expression in the wildtype, but decreased it in ΔadeRS, implying that AdeRS activates adeAB transcription in ATCC 17978. Investigation under multiple growth conditions, including the use of Biolog phenotypic microarrays, revealed resistance to pentamidine in ATCC 17978 and mutants could be altered by bioavailability of iron or utilization of different carbon sources. In conclusion, the results of this study provide evidence that AdeAB in ATCC 17978 can confer intrinsic resistance to a subset of dicationic compounds and in particular, resistance to pentamidine can be significantly altered depending on the growth conditions. en_US
dc.description.sponsorship This work was supported by the Australian National Health and Medical Research Council (Project Grant 1047509) and a Flinders Medical Research Foundation Grant to MHB and UHS. FGA was supported by AJ and IM Naylon and Playford Trust Ph.D. Scholarships. en_US
dc.identifier.citation Adams, F.G., Stroeher, U.H., Hassan, K.A., Marri, S. & Brown, M.H., (2018). Resistance to pentamidine is mediated by AdeAB, regulated by AdeRS, and influenced by growth conditions in Acinetobacter baumannii ATCC 17978. PLoS ONE 13(5): e0197412. en_US
dc.identifier.doi https://doi.org/10.1371/journal.pone.0197412 en_US
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/2328/38359
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.relation.grantnumber NHMRC/1047509 en_US
dc.rights © 2018 Adams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_US
dc.rights.holder © 2018 Adams et al. en_US
dc.rights.license CC-BY
dc.title Resistance to pentamidine is mediated by AdeAB, regulated by AdeRS, and influenced by growth conditions in Acinetobacter baumannii ATCC 17978 en_US
dc.type Article en
local.contributor.authorOrcidLookup Brown, Melissa Hackett: https://orcid.org/0000-0001-6461-7550 en_US
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