A polyamine acetyltransferase regulates the motility and biofilm formation of Acinetobacter baumannii

Abstract

Acinetobacter baumannii is a nosocomial pathogen highly resistant to environmental changes and antimicrobial treatments. Regulation of cellular motility and biofilm formation is important for its virulence, although it is poorly described at the molecular level. It has been previously reported that Acinetobacter genus specifically produces a small positively charged metabolite, polyamine 1,3-diaminopropane, that has been associated with cell motility and virulence. Here we show that A. baumannii encodes novel acetyltransferase, Dpa, that acetylates 1,3-diaminopropane, directly affecting the bacterium motility. Expression of dpa increases in bacteria that form pellicle and adhere to eukaryotic cells as compared to planktonic bacterial cells, suggesting that cell motility is linked to the pool of non-modified 1,3-diaminopropane. Indeed, deletion of dpa hinders biofilm formation and increases twitching motion confirming the impact of balancing the levels of 1,3-diaminopropane on cell motility. The crystal structure of Dpa reveals topological and functional differences from other bacterial polyamine acetyltransferases, adopting a β-swapped quaternary arrangement similar to that of eukaryotic polyamine acetyltransferases with a central size exclusion channel that sieves through the cellular polyamine pool. The structure of catalytically impaired DpaY128F in complex with the reaction product shows that binding and orientation of the polyamine substrates are conserved between different polyamine-acetyltransferases.

Antibiofilm and Antivirulence Properties of 6-Polyaminosteroid Derivatives against Antibiotic-Resistant Bacteria

“…A similar effect of the polyamine lateral chain on A. baumannii biofilms is less likely. For this species, which only produces 1,3 diaminopropane but no polyamine with longer carbon chain, it was previously shown that the addition of diverse exogenous polyamines like spermine, spermidine, cadaverine, or putrescine did not impact biofilm development [35]. However, the amphiphilicity of the molecule associated with the positive charge of amines in precise spacing may act as a biofilm disruptor, as it was previously shown [30].…”

Characterization of an Arginine Decarboxylase from Streptococcus pneumoniae by Ultrahigh-Performance Liquid Chromatography–Tandem Mass Spectrometry

“…Fonsibacter ubiquis have been shown recently to evolve into ADC [51,52], which could additionally explain our discovery of two different ADCs in pneumococcus. Information on polyamine acetyltransferases that regulate motility and biofilm formation [53], and deacetylases that utilize acetylated polyamine substrates, is also poorly described [6]. Enzymes of the pyridoxaldependent decarboxylase family, which catalyze the synthesis of polyamines, are expected to potentially utilize a variety of substrates amino acids.…”

Identification and targeting of microbial putrescine acetylation in bloodstream infections

“…aeruginosa PA1472, candidate homologs in A. baumannii and S. pneumoniae cluster separately, but map to the microbial side of the phylogenetic tree, distinct from eukaryotic homologs. Interestingly, a distinct polyamine acetyltransferase more similar to the mammalian SAT1 enzyme and not included in our phylogenetic analysis, was recently described in A. baumannii, with a narrow substrate scope predominantly limited to short chain 1,3-diaminopropane 94 . The A. baumannii candidate enzyme included in our phylogenetic analysis was not studied and its role in polyamine metabolism is unknown.…”