Retained Activity of an O25b-Specific Monoclonal Antibody against an Mcr-1-Producing Escherichia coli Sequence Type 131 Strain

Antimicrob Agents Chemother. 2018 Jun 26;62(7):e00046-18. doi: 10.1128/AAC.00046-18. Print 2018 Jul.

Abstract

Plasmid-encoded colistin resistance is emerging among extraintestinal pathogenic Escherichia coli strains, including those of the epidemic clone sequence type 131 (ST131)-H30. Mcr-1 transfers a phosphoethanolamine to the lipid A portion of lipopolysaccharide (LPS), conferring resistance to polymyxins. We investigated whether this modification changed the activity of the monoclonal antibody ASN-4, specific to the O25b side chain of ST131 LPS. We confirmed that, unlike colistin, ASN-4 retained its bactericidal and endotoxin-neutralizing activities and therefore offers a treatment option against extremely drug-resistant ST131 isolates.

Keywords: Escherichia coli ST131; mcr-1; monoclonal antibodies.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antibodies, Monoclonal / pharmacology*
  • Colistin / pharmacology
  • Drug Resistance, Multiple, Bacterial / genetics
  • Endotoxins / metabolism
  • Escherichia coli Infections / drug therapy*
  • Escherichia coli Proteins / metabolism*
  • Extraintestinal Pathogenic Escherichia coli / drug effects*
  • Extraintestinal Pathogenic Escherichia coli / genetics
  • Female
  • Humans
  • Lipopolysaccharides / chemistry
  • Mice
  • Mice, Inbred BALB C

Substances

  • Anti-Bacterial Agents
  • Antibodies, Monoclonal
  • Endotoxins
  • Escherichia coli Proteins
  • Lipopolysaccharides
  • MCR-1 protein, E coli
  • Colistin