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 journalArticle

73 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

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Colistin
Acinetobacter baumannii
Lipid A
Lipopolysaccharides
Galactosamine
Acinetobacter Infections
Antimicrobial Cationic Peptides
Acylation
Wound Infection
Cross Infection
Tandem Mass Spectrometry
Glycosylation
Sepsis
Pneumonia
Phosphates
Phosphorylation
phosphorylethanolamine

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Pelletier, M. R., Casella, L. G., Jones, J. W., Adams, M. D., Zurawski, D. V., Hazlett, K. R. O., ... Ernst, R. K. (2013). Unique structural modifications are present in the lipopolysaccharide from colistin-resistant strains of Acinetobacter baumannii. Antimicrobial agents and chemotherapy, 57(10), 4831-4840. https://doi.org/10.1128/AAC.00865-13
Pelletier, Mark R. ; Casella, Leila G. ; Jones, Jace W. ; Adams, Mark D. ; Zurawski, Daniel V. ; Hazlett, Karsten R.O. ; Doi, Yohei ; Ernst, Robert K. / Unique structural modifications are present in the lipopolysaccharide from colistin-resistant strains of Acinetobacter baumannii. In: Antimicrobial agents and chemotherapy. 2013 ; Vol. 57, No. 10. pp. 4831-4840.
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Unique structural modifications are present in the lipopolysaccharide from colistin-resistant strains of Acinetobacter baumannii. / Pelletier, Mark R.; Casella, Leila G.; Jones, Jace W.; Adams, Mark D.; Zurawski, Daniel V.; Hazlett, Karsten R.O.; Doi, Yohei; Ernst, Robert K.

In: Antimicrobial agents and chemotherapy, Vol. 57, No. 10, 01.10.2013, p. 4831-4840.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Unique structural modifications are present in the lipopolysaccharide from colistin-resistant strains of Acinetobacter baumannii

AU - Pelletier, Mark R.

AU - Casella, Leila G.

AU - Jones, Jace W.

AU - Adams, Mark D.

AU - Zurawski, Daniel V.

AU - Hazlett, Karsten R.O.

AU - Doi, Yohei

AU - Ernst, Robert K.

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N2 - 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.

AB - 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.

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