title: A global virulence regulator in Acinetobacter baumannii and its control of the phenylacetic acid catabolic pathway.
abstract: 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.
  
  
  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.
authors.forename: Gustavo M
authors.initials: GM
authors.lastname: Cerqueira
authors.forename: Xenia
authors.initials: X
authors.lastname: Kostoulias
authors.forename: Chen
authors.initials: C
authors.lastname: Khoo
authors.forename: Ibukun
authors.initials: I
authors.lastname: Aibinu
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.forename: Ana
authors.initials: A
authors.lastname: Traven
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Peleg
mesh_terms: D040981:Acinetobacter baumannii / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D018441:Biofilms / Q000254:growth & development; D005260:Female; D010861:Fimbriae, Bacterial / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D008124:Locomotion; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008807:Mice, Inbred BALB C; D010648:Phenylacetates / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000382:microbiology / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D010648:Phenylacetates; D014157:Transcription Factors; D037521:Virulence Factors; D011494:Protein Kinases; C025136:phenylacetic acid