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Effects of the Anti...
Effects of the Antimicrobial Peptide LL-37 and Innate Effector Mechanisms in Colistin-Resistant Klebsiella pneumoniae With mgrB Insertions
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- Al-Farsi, Hissa M. (author)
- Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman.
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- Al-Adwani, Salma (author)
- Karolinska Institutet
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- Ahmed, Sultan (author)
- Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.
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- Vogt, Carmen (author)
- KTH,Biomedicinsk fysik och röntgenfysik,Albanova VinnExcellence Center for Protein Technology, ProNova
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- Ambikan, Anoop T. (author)
- Karolinska Institutet
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- Leber, Anna (author)
- Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.
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- Al-Jardani, Amina (author)
- Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman.
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- Al-Azri, Saleh (author)
- Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman.
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- Al-Muharmi, Zakariya (author)
- Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Microbiol & Immunol, Muscat, Oman.
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- Toprak, Muhammet, 1973- (author)
- KTH,Biomedicinsk fysik och röntgenfysik,Albanova VinnExcellence Center for Protein Technology, ProNova
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- Giske, Christian G. (author)
- Karolinska Institutet
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- Bergman, Peter (author)
- Karolinska Institutet
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Karolinska Institutet Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden;Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman. (creator_code:org_t)
- 2019-11-14
- 2019
- English.
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In: Frontiers in Microbiology. - : FRONTIERS MEDIA SA. - 1664-302X. ; 10
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- cross-resistance
- colistin
- LL-37
- innate immunity
- zeta potential
- whole blood killing assay
- serum killing assay
- zebrafish
Publication and Content Type
- ref (subject category)
- art (subject category)
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Al-Farsi, Hissa ...
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Al-Adwani, Salma
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Ahmed, Sultan
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Vogt, Carmen
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Ambikan, Anoop T ...
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Leber, Anna
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Al-Jardani, Amin ...
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Al-Azri, Saleh
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Al-Muharmi, Zaka ...
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Toprak, Muhammet ...
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Giske, Christian ...
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Bergman, Peter
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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Frontiers in Mic ...
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Royal Institute of Technology
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Karolinska Institutet