aeruginosa is a successful and common pathogen. The genome sequence of this microorganism revealed that more than 500 genes, representing nearly 10% of the genome, have a putative role in regulation . In addition to conventional regulators involved in transcription of particular genes, e.g. sigma factors, repressors, activators or two-component response regulators, P. aeruginosa possesses several additional proteins that modulate translation, protein histone deacetylase activity biosynthesis and degradation, etc. Here we have defined the role of the GTPase TypA in the lifestyle of P. aeruginosa. TypA, also named BipA, belongs
to a superfamily of ribosome-binding GTPases within the TRAFAC class (translation factors) of GTPases [12–14]. GTPases are widely distributed molecular switches found across all bacterial species, and generally cycle between a GDP-bound “off” state and a GTP-bound “on” state [14, 15]. Collectively
they are involved in the regulation of multiple cellular processes and can C188-9 play important roles in translation, ribosome biogenesis and assembly, tRNA modification, protein translocation, cell polarity, cell division and signaling events [14, 16]. Since GTPases are widely conserved in prokaryotes and play an essential role in many important bacterial processes, they are an attractive target for novel antibiotic development . TypA is highly conserved in bacteria and shares sequence homologies to other GTPases like elongation factor G. It is found in many pathogens of significant public health importance including Vibrio cholera, Yersinia
Urocanase pestis and Mycobacterium tuberculosis. Although its precise function is still QVDOph poorly understood, TypA has been suggested to be involved in the regulation of virulence and stress responses in pathogenic Escherichia coli[18, 19] and Salmonella enterica Serovar Typhimurium , and stress responses in non-pathogenic Sinorhizobium meliloti and Bacillus subtilis. Open reading frame PA5117 is annotated as the GTPase TypA, exhibits 75% sequence homology to TypA/BipA from E. coli, and plays a role in swarming motility and biofilm formation in P. aeruginosa PAO1 . However, the role of TypA in pathogenesis of P. aeruginosa is still unknown. Here we constructed a knock-out mutant of typA in P. aeruginosa PA14 and demonstrated the involvement of TypA in the pathogenesis of P. aeruginosa using different in vitro and in vivo infection model systems. Consistent with these data, we showed using gene expression analysis that several virulence-associated genes were down-regulated in a TypA mutant during host-pathogen interaction. We also found that TypA plays a role in antibiotic resistance to a variety of different antibiotics and initial attachment leading to subsequent biofilm formation in P. aeruginosa PA14. Results TypA is involved in P.