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

Luis M Guachalla1, Katharina Ramoni1, Cecilia Varga1

  • 1Arsanis Biosciences, Vienna, Austria.

Insights

Plasmid-encoded colistin resistance is rising in extraintestinal pathogenic Escherichia coli. However, the monoclonal antibody ASN-4 remains effective against ST131 strains, offering a potential treatment for drug-resistant infections.

Area of Science:

  • Microbiology
  • Immunology
  • Drug Resistance

Background:

  • Plasmid-mediated colistin resistance is an increasing threat, particularly in extraintestinal pathogenic Escherichia coli (ExPEC) strains like the ST131-H30 clone.
  • The mcr-1 gene confers resistance to polymyxins, including colistin, by modifying the lipopolysaccharide (LPS) structure.

Purpose of the Study:

  • To determine if mcr-1-mediated LPS modification affects the activity of the monoclonal antibody ASN-4.
  • To evaluate ASN-4 as a potential therapeutic agent against colistin-resistant ST131 isolates.

Main Methods:

  • Investigated the interaction between the monoclonal antibody ASN-4 and LPS from mcr-1-positive ExPEC strains.
  • Assessed the bactericidal and endotoxin-neutralizing activities of ASN-4 against these resistant isolates.

Main Results:

  • The mcr-1 modification of LPS did not abolish the binding or activity of the monoclonal antibody ASN-4.
  • ASN-4 retained significant bactericidal and endotoxin-neutralizing capabilities against colistin-resistant ST131 isolates.

Conclusions:

  • The monoclonal antibody ASN-4 represents a promising therapeutic strategy against emerging colistin-resistant ExPEC strains, including the ST131-H30 clone.
  • ASN-4 offers a viable treatment option where colistin resistance is present, highlighting its potential in combating antimicrobial resistance.

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