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  • Al-Farsi, Hissa M.Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman. (author)

Effects of the Antimicrobial Peptide LL-37 and Innate Effector Mechanisms in Colistin-Resistant Klebsiella pneumoniae With mgrB Insertions

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-11-14
  • FRONTIERS MEDIA SA,2019
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-266309
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-266309URI
  • https://doi.org/10.3389/fmicb.2019.02632DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:142449514URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20200107
  • 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.

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  • Al-Adwani, SalmaKarolinska Institutet (author)
  • Ahmed, SultanKarolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden. (author)
  • Vogt, CarmenKTH,Biomedicinsk fysik och röntgenfysik,Albanova VinnExcellence Center for Protein Technology, ProNova(Swepub:kth)u1iann4b (author)
  • Ambikan, Anoop T.Karolinska Institutet (author)
  • Leber, AnnaKarolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden. (author)
  • Al-Jardani, AminaMinist Hlth, Cent Publ Hlth Labs, Muscat, Oman. (author)
  • Al-Azri, SalehMinist Hlth, Cent Publ Hlth Labs, Muscat, Oman. (author)
  • Al-Muharmi, ZakariyaSultan Qaboos Univ, Coll Med & Hlth Sci, Dept Microbiol & Immunol, Muscat, Oman. (author)
  • Toprak, Muhammet,1973-KTH,Biomedicinsk fysik och röntgenfysik,Albanova VinnExcellence Center for Protein Technology, ProNova(Swepub:kth)u1u3m5a2 (author)
  • Giske, Christian G.Karolinska Institutet (author)
  • Bergman, PeterKarolinska Institutet (author)
  • Karolinska InstitutetKarolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman. (creator_code:org_t)

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  • In:Frontiers in Microbiology: FRONTIERS MEDIA SA101664-302X

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