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Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline

Colistin and tigecycline are the last options against carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). Intersecting resistance determinants have been detected between these antibiotics; however, there is only limited evidence of such association. Here, we describe a colistin-resis...

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Autores principales: Zhang, Yawei, Wang, Xiaojuan, Wang, Shifu, Sun, Shijun, Li, Henan, Chen, Hongbin, Wang, Qi, Wang, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672221/
https://www.ncbi.nlm.nih.gov/pubmed/34925264
http://dx.doi.org/10.3389/fmicb.2021.756580
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author Zhang, Yawei
Wang, Xiaojuan
Wang, Shifu
Sun, Shijun
Li, Henan
Chen, Hongbin
Wang, Qi
Wang, Hui
author_facet Zhang, Yawei
Wang, Xiaojuan
Wang, Shifu
Sun, Shijun
Li, Henan
Chen, Hongbin
Wang, Qi
Wang, Hui
author_sort Zhang, Yawei
collection PubMed
description Colistin and tigecycline are the last options against carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). Intersecting resistance determinants have been detected between these antibiotics; however, there is only limited evidence of such association. Here, we describe a colistin-resistant CR-hvKP isolated from a patient with severe neonatal bacteremia treated with tigecycline as opposed to colistin before isolation of this strain, providing a clinical clue to colistin resistance under tigecycline pressure. Furthermore, an ST11-K64 KPC-2–producing, colistin-susceptible CR-hvKP strain was subjected to experimental evolution toward colistin resistance under tigecycline and colistin pressure to verify this phenomenon in vitro. The biological impact of acquiring colistin resistance on fitness and virulence was also studied. As expected, the parental strain rapidly developed colistin resistance under both tigecycline and colistin selection. However, different from the colistin resistance mechanism in the clinical strain that was due to an ISKpn26 insertion in the mgrB gene, the mutants in this study developed colistin resistance through a ∼4.4 or ∼4.6 kb deletion including the mgrB locus as well as the kdgR, yobH, yebO, yobF, cspC, ftsI, and rlmA genes. Although the virulence of the colistin-resistant mutants, as determined in the Galleria mellonella model, decreased compared with that of the parent strain, it was still higher than that of NTUH-K2044. This suggests a slight virulence cost when CR-hvKP develops colistin resistance under tigecycline or colistin pressure. Together, our results provide clinical and experimental evidence for the association between colistin resistance and tigecycline pressure in CR-hvKP, highlighting a critical issue in the clinical setting.
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spelling pubmed-86722212021-12-16 Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline Zhang, Yawei Wang, Xiaojuan Wang, Shifu Sun, Shijun Li, Henan Chen, Hongbin Wang, Qi Wang, Hui Front Microbiol Microbiology Colistin and tigecycline are the last options against carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). Intersecting resistance determinants have been detected between these antibiotics; however, there is only limited evidence of such association. Here, we describe a colistin-resistant CR-hvKP isolated from a patient with severe neonatal bacteremia treated with tigecycline as opposed to colistin before isolation of this strain, providing a clinical clue to colistin resistance under tigecycline pressure. Furthermore, an ST11-K64 KPC-2–producing, colistin-susceptible CR-hvKP strain was subjected to experimental evolution toward colistin resistance under tigecycline and colistin pressure to verify this phenomenon in vitro. The biological impact of acquiring colistin resistance on fitness and virulence was also studied. As expected, the parental strain rapidly developed colistin resistance under both tigecycline and colistin selection. However, different from the colistin resistance mechanism in the clinical strain that was due to an ISKpn26 insertion in the mgrB gene, the mutants in this study developed colistin resistance through a ∼4.4 or ∼4.6 kb deletion including the mgrB locus as well as the kdgR, yobH, yebO, yobF, cspC, ftsI, and rlmA genes. Although the virulence of the colistin-resistant mutants, as determined in the Galleria mellonella model, decreased compared with that of the parent strain, it was still higher than that of NTUH-K2044. This suggests a slight virulence cost when CR-hvKP develops colistin resistance under tigecycline or colistin pressure. Together, our results provide clinical and experimental evidence for the association between colistin resistance and tigecycline pressure in CR-hvKP, highlighting a critical issue in the clinical setting. Frontiers Media S.A. 2021-12-01 /pmc/articles/PMC8672221/ /pubmed/34925264 http://dx.doi.org/10.3389/fmicb.2021.756580 Text en Copyright © 2021 Zhang, Wang, Wang, Sun, Li, Chen, Wang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Zhang, Yawei
Wang, Xiaojuan
Wang, Shifu
Sun, Shijun
Li, Henan
Chen, Hongbin
Wang, Qi
Wang, Hui
Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline
title Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline
title_full Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline
title_fullStr Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline
title_full_unstemmed Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline
title_short Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline
title_sort emergence of colistin resistance in carbapenem-resistant hypervirulent klebsiella pneumoniae under the pressure of tigecycline
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672221/
https://www.ncbi.nlm.nih.gov/pubmed/34925264
http://dx.doi.org/10.3389/fmicb.2021.756580
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