A global virulence regulator in Acinetobacter baumannii and its control of the phenylacetic acid catabolic pathway

Cerqueira, Gustavo M., Kostoulias, Xenia, Khoo, Chen, Aibinu, Ibukun, Qu, Yue, Traven, Ana, and Peleg, Anton Y. (2014) A global virulence regulator in Acinetobacter baumannii and its control of the phenylacetic acid catabolic pathway. Journal of Infectious Diseases, 210 (1). pp. 46-55.

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Background: Acinetobacter baumannii is one of the most notorious hospital-acquired pathogens, and novel treatment strategies are desperately required. Two-component regulatory systems represent potential therapeutic targets as they mediate microorganism adaptation to changing environments, often control virulence, and are specific to bacteria. Here we describe the first global virulence regulator in A. baumannii.

Methods and Results: Using transcriptional profiling and functional assays of a deletion mutant in the A. baumannii sensor kinase gene, A1S_0574 (termed as gacS), we show that this sensor kinase regulates key virulence characteristics, including pili synthesis, biofilms, and motility, resulting in virulence attenuation in a mammalian septicemia model. Notably, we also identified that GacS regulates an operon novel to A. baumannii (paa operon), which is responsible for the metabolism of aromatic compounds. Deletion of paaE (A1S_1340) confirmed the role of this operon in A. baumannii virulence. Finally, we identified the cognate response regulator (A1S_0236) for GacS and confirmed their interaction. A1S_0236 was shown to regulate 75% of the GacS transcriptome and the same virulence phenotypes. Overexpression of A1S_0236 restored virulence in the gacS mutant.

Conclusions: Our study characterizes a global virulence regulator, which may provide an alternate therapeutic target, in one of the most troublesome hospital-acquired pathogens.

Item ID: 37409
Item Type: Article (Research - C1)
ISSN: 1537-6613
Keywords: A. baumannii; 2-component system; sensor kinase; response regulator; GacS; GacA; virulence; transcriptome; paa; phenylacetate
Funders: Australian National Health and Medical Research Council (NHMRC), Australian Research Council (ARC)
Projects and Grants: NHMRC ( APP1010114, APP1047916)
Date Deposited: 19 Feb 2015 05:20
FoR Codes: 06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060503 Microbial Genetics @ 50%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060502 Infectious Agents @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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