Inactivation of AdeABC and AdeIJK efflux pumps elicits specific nonoverlapping transcriptional and phenotypic responses in Acinetobacter baumannii.,Molecular Microbiology

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Inactivation of AdeABC and AdeIJK efflux pumps elicits specific nonoverlapping transcriptional and phenotypic responses in Acinetobacter baumannii.
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-08-28 , DOI: 10.1111/mmi.14594
Inga V Leus ₁ , Justyna Adamiak ₁ , Anhthu N Trinh ₁ , Richard D Smith ₂ , Lauren Smith ₁ , Sophie Richardson ₁ , Robert K Ernst ₂ , Helen I Zgurskaya ₁

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Multidrug resistant (MDR) strains of Acinetobacter baumannii present a serious clinical challenge. The development of antibiotic resistance in this species is enabled by efflux pumps of the Resistance‐Nodulation‐Division (RND) superfamily of proteins creating an efficient permeability barrier for antibiotics. At least three RND pumps, AdeABC, AdeIJK, and AdeFGH are encoded in the A. baumannii genome and are reported to contribute to antibiotic resistance in clinical isolates. In this study, we analyzed the contributions of AdeABC and AdeIJK in antibiotic resistance and growth physiology of the two MDR strains, AYE and AB5075. We found that not only the two pumps have nonoverlapping substrate specificities, their inactivation leads to specific nonoverlapping changes in gene expression as determined by RNA sequencing and confirmed by gene knockouts and growth phenotypes. Our results suggest that inactivation of AdeIJK elicits broader changes in the abundances of mRNAs and this response is modified in the absence of AdeB. In contrast, inactivation of AdeB leads to a focused cellular response, which is not sensitive to the activity of AdeIJK. We identified additional efflux pumps and transcriptional regulators that contribute to MDR phenotype of clinical A. baumannii isolates.

中文翻译：

AdeABC 和 AdeIJK 外排泵的失活在鲍曼不动杆菌中引起特定的非重叠转录和表型反应。

鲍曼不动杆菌的多药耐药 (MDR) 菌株是一项严峻的临床挑战。该物种抗生素耐药性的发展是由蛋白质的耐药结节分裂 (RND) 超家族的外排泵实现的，它为抗生素创造了一个有效的渗透屏障。A. baumannii中至少编码了三个 RND 泵、AdeABC、AdeIJK 和 AdeFGH基因组，据报道有助于临床分离株的抗生素耐药性。在这项研究中，我们分析了 AdeABC 和 AdeIJK 在两种 MDR 菌株 AYE 和 AB5075 的抗生素抗性和生长生理学中的贡献。我们发现不仅这两个泵具有不重叠的底物特异性，而且它们的失活会导致基因表达的特定非重叠变化，这一点由 RNA 测序确定并由基因敲除和生长表型证实。我们的结果表明，AdeIJK 的失活会引起 mRNA 丰度的更广泛变化，并且这种反应在没有 AdeB 的情况下会发生变化。相反，AdeB 的失活导致集中的细胞反应，这对 AdeIJK 的活性不敏感。A. baumannii分离株。

更新日期：2020-08-28

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