title: TypA is involved in virulence, antimicrobial resistance and biofilm formation in Pseudomonas aeruginosa.
abstract: BACKGROUND
  Pseudomonas aeruginosa is an important opportunistic human pathogen and is extremely difficult to treat due to its high intrinsic and adaptive antibiotic resistance, ability to form biofilms in chronic infections and broad arsenal of virulence factors, which are finely regulated. TypA is a GTPase that has recently been identified to modulate virulence in enteric Gram-negative pathogens.
  
  
  RESULTS
  Here, we demonstrate that mutation of typA in P. aeruginosa resulted in reduced virulence in phagocytic amoebae and human macrophage models of infection. In addition, the typA mutant was attenuated in rapid cell attachment to surfaces and biofilm formation, and exhibited reduced antibiotic resistance to ß-lactam, tetracycline and antimicrobial peptide antibiotics. Quantitative RT-PCR revealed the down-regulation, in a typA mutant, of important virulence-related genes such as those involved in regulation and assembly of the Type III secretion system, consistent with the observed phenotypes and role in virulence of P. aeruginosa.
  
  
  CONCLUSIONS
  These data suggest that TypA is a newly identified modulator of pathogenesis in P. aeruginosa and is involved in multiple virulence-related characteristics.
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces, PO Box 3640, Karlsruhe, 76021, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Neidig
authors.forename: Amy T Y
authors.initials: AT
authors.lastname: Yeung
authors.forename: Thibaut
authors.initials: T
authors.lastname: Rosay
authors.forename: Beatrix
authors.initials: B
authors.lastname: Tettmann
authors.forename: Nikola
authors.initials: N
authors.lastname: Strempel
authors.forename: Martina
authors.initials: M
authors.lastname: Rueger
authors.forename: Olivier
authors.initials: O
authors.lastname: Lesouhaitier
authors.forename: Joerg
authors.initials: J
authors.lastname: Overhage
mesh_terms: D000656:Amoeba / Q000382:microbiology; D001422:Bacterial Adhesion; D018441:Biofilms / Q000254:growth & development*; D002478:Cells, Cultured; D024881:Drug Resistance, Bacterial; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D037521:Virulence Factors; D020558:GTP Phosphohydrolases