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

Luis M Guachalla,Gábor Nagy,Ágnes Sonnevend,Katharina Ramoni,Tibor Pál,Cecilia Varga,Valéria Szijártó,Eszter Nagy,Akela Ghazawi,Michele Mutti

doi:10.1128/aac.00046-18

Abstract

ABSTRACTPlasmid-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.

Highlights

Plasmid-encoded colistin resistance is emerging among extraintestinal pathogenic Escherichia coli strains, including those of the epidemic clone sequence type 131 (ST131)-H30
We have previously reported humanized monoclonal antibodies [7] targeting the lipopolysaccharide O25b antigen associated with the ST131-H30 clone [8], the most prevalent extraintestinal pathogenic E. coli (ExPEC) lineage, responsible for a wide range of infections
We demonstrated that these monoclonal antibodies (MAbs) have complementdependent bactericidal, opsonophagocytic, and endotoxin-neutralizing activities that contribute to protection in murine models [9]

Summary

Introduction

Plasmid-encoded colistin resistance is emerging among extraintestinal pathogenic Escherichia coli strains, including those of the epidemic clone sequence type 131 (ST131)-H30. We demonstrated that these monoclonal antibodies (MAbs) have complementdependent bactericidal, opsonophagocytic, and endotoxin-neutralizing activities that contribute to protection in murine models [9]. We show that all three mechanisms of action of an O25bspecific MAb, ASN-4, were retained against E. coli ST131-H30 isolates producing Mcr-1.

Results

Conclusion