title: Unique structural modifications are present in the lipopolysaccharide from colistin-resistant strains of Acinetobacter baumannii.
abstract: Acinetobacter baumannii is a nosocomial opportunistic pathogen that can cause severe infections, including hospital-acquired pneumonia, wound infections, and sepsis. Multidrug-resistant (MDR) strains are prevalent, further complicating patient treatment. Due to the increase in MDR strains, the cationic antimicrobial peptide colistin has been used to treat A. baumannii infections. Colistin-resistant strains of A. baumannii with alterations to the lipid A component of lipopolysaccharide (LPS) have been reported; specifically, the lipid A structure was shown to be hepta-acylated with a phosphoethanolamine (pEtN) modification present on one of the terminal phosphate residues. Using a tandem mass spectrometry platform, we provide definitive evidence that the lipid A isolated from colistin-resistant A. baumannii MAC204 LPS contains a novel structure corresponding to a diphosphoryl hepta-acylated lipid A structure with both pEtN and galactosamine (GalN) modifications. To correlate our structural studies with clinically relevant samples, we characterized colistin-susceptible and -resistant isolates obtained from patients. These results demonstrated that the clinical colistin-resistant isolate had the same pEtN and GalN modifications as those seen in the laboratory-adapted A. baumannii strain MAC204. In summary, this work has shown complete structure characterization including the accurate assignment of acylation, phosphorylation, and glycosylation of lipid A from A. baumannii, which are important for resistance to colistin.
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, Maryland, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Pelletier
authors.forename: Leila G
authors.initials: LG
authors.lastname: Casella
authors.forename: Jace W
authors.initials: JW
authors.lastname: Jones
authors.forename: Mark D
authors.initials: MD
authors.lastname: Adams
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Zurawski
authors.forename: Karsten R O
authors.initials: KR
authors.lastname: Hazlett
authors.forename: Yohei
authors.initials: Y
authors.lastname: Doi
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ernst
mesh_terms: D040981:Acinetobacter baumannii / Q000737:chemistry* / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002853:Chromatography, Liquid; D003091:Colistin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000737:chemistry*; D013058:Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D003091:Colistin