Physiological Roles of an Acinetobacter -specific σ Factor.

Autor:	Bacon EE; Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.; Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI, USA., Myers KS; Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI, USA.; Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, WI, USA., Iruegas-López R; Institute of Cell Biology and Neuroscience, Goethe University Frankfurt, Germany., Banta AB; Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.; Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI, USA., Place M; Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI, USA., Ebersberger I; Institute of Cell Biology and Neuroscience, Goethe University Frankfurt, Germany.; Senckenberg Biodiversity and Climate Research Centre (S-BIKF), Frankfurt, Germany.; LOEWE Center for Translational Biodiversity Genomics (TBG), Frankfurt, Germany., Peters JM; Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.; Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI, USA.; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.; Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.; Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, WI, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 08. Date of Electronic Publication: 2024 Jul 08.
DOI:	10.1101/2024.07.08.602572
Abstrakt:	The Gram-negative pathogen Acinetobacter baumannii is considered an "urgent threat" to human health due to its propensity to become antibiotic resistant. Understanding the distinct regulatory paradigms used by A. baumannii to mitigate cellular stresses may uncover new therapeutic targets. Many γ-proteobacteria use the extracytoplasmic function (ECF) σ factor, RpoE, to invoke envelope homeostasis networks in response to stress. Acinetobacter species contain the poorly characterized ECF "SigAb;" however, it is unclear if SigAb has the same physiological role as RpoE. Here, we show that SigAb is a metal stress-responsive ECF that appears unique to Acinetobacter species and distinct from RpoE. We combine promoter mutagenesis, motif scanning, and ChIP-seq to define the direct SigAb regulon, which consists of sigAb itself, the stringent response mediator, relA , and the uncharacterized small RNA, " sabS ." However, RNA-seq of strains overexpressing SigAb revealed a large, indirect regulon containing hundreds of genes. Metal resistance genes are key elements of the indirect regulon, as CRISPRi knockdown of sigAb or sabS resulted in increased copper sensitivity and excess copper induced SigAb-dependent transcription. Further, we found that two uncharacterized genes in the sigAb operon, " aabA " and " aabB ", have anti-SigAb activity. Finally, employing a targeted Tn-seq approach that uses CRISPR-associated transposons, we show that sigAb , aabA , and aabB are important for fitness even during optimal growth conditions. Our work reveals new physiological roles for SigAb and SabS, provides a novel approach for assessing gene fitness, and highlights the distinct regulatory architecture of A. baumannii . Competing Interests: Competing Interest None.
Databáze:	MEDLINE
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