Co-occurrence of mcr-1 and mcr-8 genes in a multidrug-resistant Klebsiella pneumoniae from a 2015 clinical isolate.

Sharif Hala; C P Antony; Afaque Ahmad Imtiyaz Momin; M Alshehri; Fathia Ben Rached; G Al-Ahmadi; S Zakri; M Baadhaim; A Alsaedi; O A Al Thaqafi; Stefan T. Arold; A Al-Amri; Arnab Pain

doi:10.1016/j.ijantimicag.2021.106303

Co-occurrence of mcr-1 and mcr-8 genes in a multidrug-resistant Klebsiella pneumoniae from a 2015 clinical isolate.

Sharif Hala, C P Antony, Afaque Ahmad Imtiyaz Momin, M Alshehri, Fathia Ben Rached, G Al-Ahmadi, S Zakri, M Baadhaim, A Alsaedi, O A Al Thaqafi, Stefan T. Arold, A Al-Amri, Arnab Pain

Research output: Contribution to journal › Article › peer-review

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Abstract

Polymyxin E (colistin) is among the last-resort antibiotics used to treat carbapenem-resistant Enterobacteriaceae-related infections [1]. Colistin had been discontinued for human use since it was found to be associated with nephrotoxicity and neurotoxicity, however, since the 1990s, clinicians were required to reconsider the clinical value of a modified version as a last resort antibiotic. Currently, single plasmid-mediated mobile colistin resistance (mcr) gene is recognized as a global threat, but multiple mcr gene combinations in the same pathogen are rarely identified [2]. Membrane binding domains in MCR proteins are necessary for membrane charge modifications involved in the colistin resistance mechanism [3]. Wang et al. discussed the first mcr-8 containing isolate of Klebsiella pneumoniae (KP) with a high minimum inhibitory concentration (MIC) to colistin in a Chinese hospital in 2016, which was prior to the discovery of the mcr-8 gene in 2017 from a pig farm in China related to colistin usage in animals [3]. Typically, mcr-variants are investigated through molecular identification tools or next-generation sequencing (NGS), which is not routinely implemented in clinical molecular biology laboratories. Such studies identified a close evolutionary relationship between mcr and phosphoethanolamine transferase (eptA) of Neisseria that is known to induce colistin resistance [3]. Multiple variants of mcr genes including co-occurrences in the same bacterial strain in the clinic has been identified through epidemiological surveillance of disease-causing pathogens. Continuous monitoring and identification of clinical cases that harbor unique mcr-variants is essential for understanding and monitoring colistin resistant bacteria. In this study, we identified a unique combination of colistin-resistance genes in a multidrug-resistant (MDR) KP clinical isolate and explored the role of the variant mcr genes in colistin resistance.

Original language	English (US)
Pages (from-to)	106303
Journal	International Journal of Antimicrobial Agents
DOIs	https://doi.org/10.1016/j.ijantimicag.2021.106303
State	Published - Feb 16 2021

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10.1016/j.ijantimicag.2021.106303

https://repository.kaust.edu.sa/bitstream/10754/667533/1/E-SSM-Sinica.pdf

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Hala, S., Antony, C. P., Momin, A. A. I., Alshehri, M., Ben Rached, F., Al-Ahmadi, G., Zakri, S., Baadhaim, M., Alsaedi, A., Thaqafi, O. A. A., Arold, S. T., Al-Amri, A., & Pain, A. (2021). Co-occurrence of mcr-1 and mcr-8 genes in a multidrug-resistant Klebsiella pneumoniae from a 2015 clinical isolate. International Journal of Antimicrobial Agents, 106303. https://doi.org/10.1016/j.ijantimicag.2021.106303

@article{c2acaefc78444919b676bb348653e498,

title = "Co-occurrence of mcr-1 and mcr-8 genes in a multidrug-resistant Klebsiella pneumoniae from a 2015 clinical isolate.",

abstract = "Polymyxin E (colistin) is among the last-resort antibiotics used to treat carbapenem-resistant Enterobacteriaceae-related infections [1]. Colistin had been discontinued for human use since it was found to be associated with nephrotoxicity and neurotoxicity, however, since the 1990s, clinicians were required to reconsider the clinical value of a modified version as a last resort antibiotic. Currently, single plasmid-mediated mobile colistin resistance (mcr) gene is recognized as a global threat, but multiple mcr gene combinations in the same pathogen are rarely identified [2]. Membrane binding domains in MCR proteins are necessary for membrane charge modifications involved in the colistin resistance mechanism [3]. Wang et al. discussed the first mcr-8 containing isolate of Klebsiella pneumoniae (KP) with a high minimum inhibitory concentration (MIC) to colistin in a Chinese hospital in 2016, which was prior to the discovery of the mcr-8 gene in 2017 from a pig farm in China related to colistin usage in animals [3]. Typically, mcr-variants are investigated through molecular identification tools or next-generation sequencing (NGS), which is not routinely implemented in clinical molecular biology laboratories. Such studies identified a close evolutionary relationship between mcr and phosphoethanolamine transferase (eptA) of Neisseria that is known to induce colistin resistance [3]. Multiple variants of mcr genes including co-occurrences in the same bacterial strain in the clinic has been identified through epidemiological surveillance of disease-causing pathogens. Continuous monitoring and identification of clinical cases that harbor unique mcr-variants is essential for understanding and monitoring colistin resistant bacteria. In this study, we identified a unique combination of colistin-resistance genes in a multidrug-resistant (MDR) KP clinical isolate and explored the role of the variant mcr genes in colistin resistance.",

author = "Sharif Hala and Antony, {C P} and Momin, {Afaque Ahmad Imtiyaz} and M Alshehri and {Ben Rached}, Fathia and G Al-Ahmadi and S Zakri and M Baadhaim and A Alsaedi and Thaqafi, {O A Al} and Arold, {Stefan T.} and A Al-Amri and Arnab Pain",

note = "KAUST Repository Item: Exported on 2021-02-23 Acknowledged KAUST grant number(s): BAS/1/1020-01-01, BAS/1/1056-01-01, URF/1/1976-25 Acknowledgements: We wish to thank members of the Infectious Disease Department and the Pathology Laboratory at King Khaled hospital in the Ministry of the National Guards – Health Affairs Western region for their support of our research. We also wish to acknowledge the Bioscience core laboratory at KAUST for their help with the sequencing operations. We thank Malak Haidar from KAUST Pathogen Genomics Laboratory for the technical help. We also acknowledge help from the team of curators at the Institut Pasteur MLST system (Paris, France) for importing novel alleles, profiles, and/or isolates at http://bigsdb.pasteur.fr.",

year = "2021",

month = feb,

day = "16",

doi = "10.1016/j.ijantimicag.2021.106303",

language = "English (US)",

pages = "106303",

journal = "International Journal of Antimicrobial Agents",

issn = "0924-8579",

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Hala, S, Antony, CP, Momin, AAI, Alshehri, M, Ben Rached, F, Al-Ahmadi, G, Zakri, S, Baadhaim, M, Alsaedi, A, Thaqafi, OAA, Arold, ST, Al-Amri, A & Pain, A 2021, 'Co-occurrence of mcr-1 and mcr-8 genes in a multidrug-resistant Klebsiella pneumoniae from a 2015 clinical isolate.', International Journal of Antimicrobial Agents, pp. 106303. https://doi.org/10.1016/j.ijantimicag.2021.106303

TY - JOUR

T1 - Co-occurrence of mcr-1 and mcr-8 genes in a multidrug-resistant Klebsiella pneumoniae from a 2015 clinical isolate.

AU - Hala, Sharif

AU - Antony, C P

AU - Momin, Afaque Ahmad Imtiyaz

AU - Alshehri, M

AU - Ben Rached, Fathia

AU - Al-Ahmadi, G

AU - Zakri, S

AU - Baadhaim, M

AU - Alsaedi, A

AU - Thaqafi, O A Al

AU - Arold, Stefan T.

AU - Al-Amri, A

AU - Pain, Arnab

N1 - KAUST Repository Item: Exported on 2021-02-23 Acknowledged KAUST grant number(s): BAS/1/1020-01-01, BAS/1/1056-01-01, URF/1/1976-25 Acknowledgements: We wish to thank members of the Infectious Disease Department and the Pathology Laboratory at King Khaled hospital in the Ministry of the National Guards – Health Affairs Western region for their support of our research. We also wish to acknowledge the Bioscience core laboratory at KAUST for their help with the sequencing operations. We thank Malak Haidar from KAUST Pathogen Genomics Laboratory for the technical help. We also acknowledge help from the team of curators at the Institut Pasteur MLST system (Paris, France) for importing novel alleles, profiles, and/or isolates at http://bigsdb.pasteur.fr.

PY - 2021/2/16

Y1 - 2021/2/16

N2 - Polymyxin E (colistin) is among the last-resort antibiotics used to treat carbapenem-resistant Enterobacteriaceae-related infections [1]. Colistin had been discontinued for human use since it was found to be associated with nephrotoxicity and neurotoxicity, however, since the 1990s, clinicians were required to reconsider the clinical value of a modified version as a last resort antibiotic. Currently, single plasmid-mediated mobile colistin resistance (mcr) gene is recognized as a global threat, but multiple mcr gene combinations in the same pathogen are rarely identified [2]. Membrane binding domains in MCR proteins are necessary for membrane charge modifications involved in the colistin resistance mechanism [3]. Wang et al. discussed the first mcr-8 containing isolate of Klebsiella pneumoniae (KP) with a high minimum inhibitory concentration (MIC) to colistin in a Chinese hospital in 2016, which was prior to the discovery of the mcr-8 gene in 2017 from a pig farm in China related to colistin usage in animals [3]. Typically, mcr-variants are investigated through molecular identification tools or next-generation sequencing (NGS), which is not routinely implemented in clinical molecular biology laboratories. Such studies identified a close evolutionary relationship between mcr and phosphoethanolamine transferase (eptA) of Neisseria that is known to induce colistin resistance [3]. Multiple variants of mcr genes including co-occurrences in the same bacterial strain in the clinic has been identified through epidemiological surveillance of disease-causing pathogens. Continuous monitoring and identification of clinical cases that harbor unique mcr-variants is essential for understanding and monitoring colistin resistant bacteria. In this study, we identified a unique combination of colistin-resistance genes in a multidrug-resistant (MDR) KP clinical isolate and explored the role of the variant mcr genes in colistin resistance.

AB - Polymyxin E (colistin) is among the last-resort antibiotics used to treat carbapenem-resistant Enterobacteriaceae-related infections [1]. Colistin had been discontinued for human use since it was found to be associated with nephrotoxicity and neurotoxicity, however, since the 1990s, clinicians were required to reconsider the clinical value of a modified version as a last resort antibiotic. Currently, single plasmid-mediated mobile colistin resistance (mcr) gene is recognized as a global threat, but multiple mcr gene combinations in the same pathogen are rarely identified [2]. Membrane binding domains in MCR proteins are necessary for membrane charge modifications involved in the colistin resistance mechanism [3]. Wang et al. discussed the first mcr-8 containing isolate of Klebsiella pneumoniae (KP) with a high minimum inhibitory concentration (MIC) to colistin in a Chinese hospital in 2016, which was prior to the discovery of the mcr-8 gene in 2017 from a pig farm in China related to colistin usage in animals [3]. Typically, mcr-variants are investigated through molecular identification tools or next-generation sequencing (NGS), which is not routinely implemented in clinical molecular biology laboratories. Such studies identified a close evolutionary relationship between mcr and phosphoethanolamine transferase (eptA) of Neisseria that is known to induce colistin resistance [3]. Multiple variants of mcr genes including co-occurrences in the same bacterial strain in the clinic has been identified through epidemiological surveillance of disease-causing pathogens. Continuous monitoring and identification of clinical cases that harbor unique mcr-variants is essential for understanding and monitoring colistin resistant bacteria. In this study, we identified a unique combination of colistin-resistance genes in a multidrug-resistant (MDR) KP clinical isolate and explored the role of the variant mcr genes in colistin resistance.

UR - http://hdl.handle.net/10754/667533

UR - https://linkinghub.elsevier.com/retrieve/pii/S0924857921000339

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DO - 10.1016/j.ijantimicag.2021.106303

M3 - Article

C2 - 33592301

SN - 0924-8579

SP - 106303

JO - International Journal of Antimicrobial Agents

JF - International Journal of Antimicrobial Agents

ER -

Co-occurrence of mcr-1 and mcr-8 genes in a multidrug-resistant Klebsiella pneumoniae from a 2015 clinical isolate.

Abstract

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A novel multidrug-resistant Klebsiella pneumoniae strain harboring three co-occurring mcr colistin resistance genes

A novel multidrug resistant Klebsiella pneumoniae strain harboring three co-occurring colistin resistance genes

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Co-occurrence of mcr-1 and mcr-8 genes in a multidrug-resistant Klebsiella pneumoniae from a 2015 clinical isolate.

Abstract

UN SDGs

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A novel multidrug-resistant Klebsiella pneumoniae strain harboring three co-occurring mcr colistin resistance genes

A novel multidrug resistant Klebsiella pneumoniae strain harboring three co-occurring colistin resistance genes

Cite this