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Effects of the Antimicrobial Peptide LL-37 and Innate Effector Mechanisms in Colistin-Resistant Klebsiella pneumoniae With mgrB Insertions
Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman..
Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Sultan Qaboos Univ, Coll Agr & Marine Sci, Dept Anim & Vet Sci, Muscat, Oman..
Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden..
KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.ORCID-id: 0000-0003-3095-0608
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2019 (Engelska)Ingår i: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, artikel-id 2632Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background Colistin is a polypeptide antibiotic drug that targets lipopolysaccharides in the outer membrane of Gram-negative bacteria. Inactivation of the mgrB-gene is a common mechanism behind colistin-resistance in Klebsiella pneumoniae (Kpn). Since colistin is a cyclic polypeptide, it may exhibit cross-resistance with the antimicrobial peptide LL-37, and with other innate effector mechanisms, but previous results are inconclusive. Objective To study potential cross-resistance between colistin and LL-37, as well as with other innate effector mechanisms, and to compare virulence of colistin-resistant and susceptible Kpn strains. Materials/Methods Carbapenemase-producing Kpn from Oman (n = 17) were subjected to antimicrobial susceptibility testing and whole genome sequencing. Susceptibility to colistin and LL-37 was studied. The surface charge was determined by zeta-potential measurements and the morphology of treated bacteria was analyzed with electron microscopy. Bacterial survival was assessed in human whole blood and serum, as well as in a zebrafish infection-model. Results Genome-analysis revealed insertion-sequences in the mgrB gene, as a cause of colistin resistance in 8/17 isolates. Colistin-resistant (Col-R) isolates were found to be more resistant to LL-37 compared to colistin-susceptible (Col-S) isolates, but only at concentrations >= 50 mu g/ml. There was no significant difference in surface charge between the isolates. The morphological changes were similar in both Col-R and Col-S isolates after exposure to LL-37. Finally, no survival difference between the Col-R and Col-S isolates was observed in whole blood or serum, or in zebrafish embryos. Conclusion Cross-resistance between colistin and LL-37 was observed at elevated concentrations of LL-37. However, Col-R and Col-S isolates exhibited similar survival in serum and whole blood, and in a zebrafish infection-model, suggesting that cross-resistance most likely play a limited role during physiological conditions. However, it cannot be ruled out that the observed cross-resistance could be relevant in conditions where LL-37 levels reach high concentrations, such as during infection or inflammation.

Ort, förlag, år, upplaga, sidor
FRONTIERS MEDIA SA , 2019. Vol. 10, artikel-id 2632
Nyckelord [en]
cross-resistance, colistin, LL-37, innate immunity, zeta potential, whole blood killing assay, serum killing assay, zebrafish
Nationell ämneskategori
Klinisk medicin
Identifikatorer
URN: urn:nbn:se:kth:diva-266309DOI: 10.3389/fmicb.2019.02632ISI: 000501260900001PubMedID: 31803163Scopus ID: 2-s2.0-85076028573OAI: oai:DiVA.org:kth-266309DiVA, id: diva2:1383039
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QC 20200107

Tillgänglig från: 2020-01-07 Skapad: 2020-01-07 Senast uppdaterad: 2020-01-09Bibliografiskt granskad

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Vogt, CarmenToprak, Muhammet

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Biomedicinsk fysik och röntgenfysikAlbanova VinnExcellence Center for Protein Technology, ProNova
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