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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005284naa a2200577 4500
001oai:DiVA.org:kth-266309
003SwePub
008200107s2019 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:142449514
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-2663092 URI
0247 a https://doi.org/10.3389/fmicb.2019.026322 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1424495142 URI
040 a (SwePub)kthd (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Al-Farsi, Hissa M.u Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman.4 aut
2451 0a Effects of the Antimicrobial Peptide LL-37 and Innate Effector Mechanisms in Colistin-Resistant Klebsiella pneumoniae With mgrB Insertions
264 c 2019-11-14
264 1b FRONTIERS MEDIA SA,c 2019
338 a print2 rdacarrier
500 a QC 20200107
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicin0 (SwePub)3022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicine0 (SwePub)3022 hsv//eng
653 a cross-resistance
653 a colistin
653 a LL-37
653 a innate immunity
653 a zeta potential
653 a whole blood killing assay
653 a serum killing assay
653 a zebrafish
7001 a Al-Adwani, Salmau Karolinska Institutet4 aut
7001 a Ahmed, Sultanu Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.4 aut
7001 a Vogt, Carmenu KTH,Biomedicinsk fysik och röntgenfysik,Albanova VinnExcellence Center for Protein Technology, ProNova4 aut0 (Swepub:kth)u1iann4b
7001 a Ambikan, Anoop T.u Karolinska Institutet4 aut
7001 a Leber, Annau Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.4 aut
7001 a Al-Jardani, Aminau Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman.4 aut
7001 a Al-Azri, Salehu Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman.4 aut
7001 a Al-Muharmi, Zakariyau Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Microbiol & Immunol, Muscat, Oman.4 aut
7001 a Toprak, Muhammet,d 1973-u KTH,Biomedicinsk fysik och röntgenfysik,Albanova VinnExcellence Center for Protein Technology, ProNova4 aut0 (Swepub:kth)u1u3m5a2
7001 a Giske, Christian G.u Karolinska Institutet4 aut
7001 a Bergman, Peteru Karolinska Institutet4 aut
7102 a Karolinska Institutetb Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.;Minist Hlth, Cent Publ Hlth Labs, Muscat, Oman.4 org
7730 t Frontiers in Microbiologyd : FRONTIERS MEDIA SAg 10q 10x 1664-302X
8564 u https://www.frontiersin.org/articles/10.3389/fmicb.2019.02632/pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-266309
8564 8u https://doi.org/10.3389/fmicb.2019.02632
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:142449514

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