Unique structural modifications are present in the lipopolysaccharide from colistin-resistant strains of Acinetobacter baumannii

Mark R. Pelletier, Leila G. Casella, Jace W. Jones, Mark D. Adams, Daniel V. Zurawski, Karsten R.O. Hazlett, Yohei Doi, Robert K. Ernst

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4831-4840
Number of pages10
JournalAntimicrobial agents and chemotherapy
Volume57
Issue number10
DOIs
Publication statusPublished - 01-10-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Unique structural modifications are present in the lipopolysaccharide from colistin-resistant strains of Acinetobacter baumannii'. Together they form a unique fingerprint.

Cite this