title: Substrate specificity and function of acetylpolyamine amidohydrolases from Pseudomonas aeruginosa.
abstract: BACKGROUND
  Pseudomonas aeruginosa, a Gram-negative, aerobic coccobacillus bacterium is an opportunistic human pathogen and worldwide the fourth most common cause of hospital-acquired infections which are often high mortality such as ventilator-associated pneumoniae. The polyamine metabolism of P. aeruginosa and particularly the deacetylation of acetylpolyamines has been little studied up to now. Results with other bacterial pathogens e.g., Y. pestis suggest that polyamines may be involved in the formation of biofilms or confer resistance against certain antibiotics.
  
  
  RESULTS
  To elucidate the role of acetylpolyamines and their enzymatic deacetylation in more detail, all three putative acetylpolyamine amidohydrolases (APAHs) from P. aeruginosa have been expressed in enzymatic active form. The APAHs PA0321 and PA1409 are shown to be true polyamine deacetylases, whereas PA3774 is not able to deacetylate acetylated polyamines. Every APAH can hydrolyze trifluoroacetylated lysine-derivatives, but only PA1409 and much more efficiently PA3774 can also process the plain acetylated lysine substrate. P. aeruginosa is able to utilize acetylcadaverine and acetylputrescine as a carbon source under glucose starvation. If either the PA0321 or the PA1409 but not the PA3774 gene is disrupted, the growth of P. aeruginosa is reduced and delayed. In addition, we were able to show that the APAH inhibitors SAHA and SATFMK induce biofilm formation in both PA14 and PAO1 wildtype strains.
  
  
  CONCLUSIONS
  P. aeruginosa has two functional APAHs, PA0321 and PA1409 which enable the utilization of acetylpolyamines for the metabolism of P. aeruginosa. In contrast, the physiological role of the predicted APAH, PA3774, remains to be elucidated. Its ability to deacetylate synthetic acetylated lysine substrates points to a protein deacetylation functionality with yet unknown substrates.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Haardtring 100, 64295, Darmstadt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Krämer
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces, 76021, Karlsruhe, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Herzer
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces, 76021, Karlsruhe, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Overhage
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Haardtring 100, 64295, Darmstadt, Germany. franz-josef.meyer-almes@h-da.de.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Meyer-Almes
mesh_terms: D000595:Amino Acid Sequence; D000619:Aminohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D016415:Sequence Alignment; D013379:Substrate Specificity; D000581:Amidohydrolases
chemical_list: D000619:Aminohydrolases; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; C058087:acetylpolyamine amidohydrolase; D000581:Amidohydrolases; C433811:HDAC6 protein, human