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Published on: December 23, 2022
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.
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.
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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