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Colistin Resistance Mechanisms in Human and Veterinary Klebsiella pneumoniae Isolates

Affiliation
Institute of Medical Microbiology and Infection Control, Hospital of the Johann Wolfgang von Goethe University, D-60596 Frankfurt am Main, Germany
Tietgen, Manuela;
Affiliation
Institute of Medical Microbiology and Infection Control, Hospital of the Johann Wolfgang von Goethe University, D-60596 Frankfurt am Main, Germany
Sedlaczek, Lisa;
ORCID
0000-0001-8677-9454
Affiliation
Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50935 Cologne, Germany
Higgins, Paul G.;
Affiliation
Federal Office of Consumer Protection and Food Safety, D-10117 Berlin, Germany
Kaspar, Heike;
ORCID
0000-0001-6167-1340
Affiliation
Institute of Hygiene and Infectious Diseases of Animals, Justus Liebig University Giessen, D-35392 Giessen, Germany
Ewers, Christa;
ORCID
0000-0001-6896-5309
Affiliation
Institute of Medical Microbiology and Infection Control, Hospital of the Johann Wolfgang von Goethe University, D-60596 Frankfurt am Main, Germany
Göttig, Stephan

Colistin (polymyxin E) is increasingly used as a last-resort antibiotic for the treatment of severe infections with multidrug-resistant Gram-negative bacteria. In contrast to human medicine, colistin is also used in veterinary medicine for metaphylaxis. Our objective was to decipher common colistin resistance mechanisms in Klebsiella pneumoniae isolates from animals. In total, 276 veterinary K. pneumoniae isolates, derived from companion animals or livestock, and 12 isolates from human patients were included for comparison. Six out of 276 veterinary isolates were colistin resistant (2.2%). Human isolates belonging to high-risk clonal lineages (e.g., ST15, ST101, ST258), displayed multidrug-resistant phenotypes and harboured many resistance genes compared to the veterinary isolates. However, the common colistin resistance mechanism in both human and animal K. pneumoniae isolates were diverse alterations of MgrB, a critical regulator of lipid A modification. Additionally, deleterious variations of lipopolysaccharide (LPS)-associated proteins (e.g., PmrB P95L, PmrE P89L, LpxB A152T) were identified. Phylogenetic analysis and mutation patterns in genes encoding LPS-associated proteins indicated that colistin resistance mechanisms developed independently in human and animal isolates. Since only very few antibiotics remain to treat infections with MDR bacteria, it is important to further analyse resistance mechanisms and the dissemination within different isolates and sources.

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