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:	Yawei Zhang, Xiaojuan Wang, Shifu Wang, Shijun Sun, Henan Li, Hongbin Chen, Qi Wang, Hui Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	hypervirulent Klebsiella pneumonia colistin resistance experimental evolution virulence fitness Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0d2fd7a59bf74394820480dcd404e202
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spelling	oai:doaj.org-article:0d2fd7a59bf74394820480dcd404e2022021-12-02T00:35:27ZEmergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline1664-302X10.3389/fmicb.2021.756580https://doaj.org/article/0d2fd7a59bf74394820480dcd404e2022021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.756580/fullhttps://doaj.org/toc/1664-302XColistin 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.Yawei ZhangXiaojuan WangShifu WangShijun SunHenan LiHongbin ChenQi WangHui WangFrontiers Media S.A.articlehypervirulent Klebsiella pneumoniacolistin resistanceexperimental evolutionvirulencefitnessMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypervirulent Klebsiella pneumonia colistin resistance experimental evolution virulence fitness Microbiology QR1-502
spellingShingle	hypervirulent Klebsiella pneumonia colistin resistance experimental evolution virulence fitness Microbiology QR1-502 Yawei Zhang Xiaojuan Wang Shifu Wang Shijun Sun Henan Li Hongbin Chen Qi Wang Hui Wang Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline
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.
format	article
author	Yawei Zhang Xiaojuan Wang Shifu Wang Shijun Sun Henan Li Hongbin Chen Qi Wang Hui Wang
author_facet	Yawei Zhang Xiaojuan Wang Shifu Wang Shijun Sun Henan Li Hongbin Chen Qi Wang Hui Wang
author_sort	Yawei Zhang
title	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_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_sort	emergence of colistin resistance in carbapenem-resistant hypervirulent klebsiella pneumoniae under the pressure of tigecycline
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0d2fd7a59bf74394820480dcd404e202
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Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline

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