Colistin Resistance in Gram-Negative Bacteria: Mechanisms, Transmission, and Novel Intervention Strategies

Shah Zeb; Arzoo Nazir; Muhammad Fazal Hameed; Sadia Ikram; Syed Zeeshan Haider Naqvi; Muhammad Shoaib; Patrick Butaye; Zhiqiang Wang; Ruichao Li; Xiaoyu Lu

doi:10.3390/microorganisms14010173

Colistin Resistance in Gram-Negative Bacteria: Mechanisms, Transmission, and Novel Intervention Strategies

Shah Zeb
, Arzoo Nazir
, Muhammad Fazal Hameed
, Sadia Ikram
, Syed Zeeshan Haider Naqvi
, Muhammad Shoaib^*
, Patrick Butaye
, Zhiqiang Wang
, Ruichao Li
, Xiaoyu Lu^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

8 Citations (Scopus)

9 Downloads (CityUHK Scholars)

Abstract

Multidrug resistance (MDR) in Gram-negative bacteria is a global issue and needs to be addressed urgently. MDR can emerge through genetic mutations and horizontal gene transfer and deteriorate under antibiotic selective pressure. The emergence of resistance to last-resort antibiotics, which are used to treat MDR bacteria, is of particular concern. Colistin has been recognized as a last-line antibiotic for the treatment of MDR Gram-negative bacterial infections caused by Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Recently, the increasing reports of colistin resistance pose a significant threat to public health, caused by both acquired and intrinsic mechanisms. The review aimed to elucidate the trends in colistin resistance, the use of colistin in human and veterinary medicine, underlying resistance mechanisms and transmission pathways, and potential mitigation of this emerging threat through novel intervention strategies. Colistin resistance is mediated by plasmid-encoded phosphoethanolamine transferases (mcr-1 to mcr-10) and chromosomal lipid A remodeling pathways. In Escherichia coli, resistance involves mcr-1–10, acrB efflux mutations, pmrA/pmrB, arnBCADTEF, and mgrB inactivation. Klebsiella pneumoniae exhibits mcr-1, mcr-8, mcr-9, mgrB disruption and phoP/phoQ–pmrAB activation. Acinetobacter baumannii harbors mcr-1–4, while Salmonella enterica and Enterobacter spp. carry mcr variants with arnBCADTEF induction. Therapeutic options include adjunct strategies such as antimicrobial peptides, nanomaterials, therapeutic adjuvants, CRISPR-Cas9-based gene editing, probiotics, vaccines, and immune modulators to restore susceptibility. This review identified that specific and wide actions are required to handle the growing colistin resistance, including genomic surveillance, tracing novel resistance mechanisms, and the application of alternative management strategies. The One Health approach is considered a key strategy to address this growing issue.

© 2026 by the authors.

Original language	English
Article number	173
Number of pages	28
Journal	Microorganisms
Volume	14
Issue number	1
Online published	13 Jan 2026
DOIs	https://doi.org/10.3390/microorganisms14010173
Publication status	Published - Jan 2026

Funding

This work was supported by the National Key Research and Development Program of China (2024YFC3406300), the National Key Laboratory of Veterinary Public Health and Safety Open Project Fund (2024SKLVPHS04), the Fundamental Research Funds of Taizhou University (TZXYQD2024A034), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

colistin resistance
Gram-negative bacteria
intervention strategies
mcr genes
One Health approach

Publisher's Copyright Statement

This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

Access Output

10.3390/microorganisms14010173

428661879.pdfFinal Published version, 2.19 MBLicence: CC BY

Other Access Options

Check CityUHK Library

Permanent Link

Right click to copy link

Cite this

@article{4d8bcce374d64cb0b7f58b184925ed1b,

title = "Colistin Resistance in Gram-Negative Bacteria: Mechanisms, Transmission, and Novel Intervention Strategies",

abstract = "Multidrug resistance (MDR) in Gram-negative bacteria is a global issue and needs to be addressed urgently. MDR can emerge through genetic mutations and horizontal gene transfer and deteriorate under antibiotic selective pressure. The emergence of resistance to last-resort antibiotics, which are used to treat MDR bacteria, is of particular concern. Colistin has been recognized as a last-line antibiotic for the treatment of MDR Gram-negative bacterial infections caused by Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Recently, the increasing reports of colistin resistance pose a significant threat to public health, caused by both acquired and intrinsic mechanisms. The review aimed to elucidate the trends in colistin resistance, the use of colistin in human and veterinary medicine, underlying resistance mechanisms and transmission pathways, and potential mitigation of this emerging threat through novel intervention strategies. Colistin resistance is mediated by plasmid-encoded phosphoethanolamine transferases (mcr-1 to mcr-10) and chromosomal lipid A remodeling pathways. In Escherichia coli, resistance involves mcr-1–10, acrB efflux mutations, pmrA/pmrB, arnBCADTEF, and mgrB inactivation. Klebsiella pneumoniae exhibits mcr-1, mcr-8, mcr-9, mgrB disruption and phoP/phoQ–pmrAB activation. Acinetobacter baumannii harbors mcr-1–4, while Salmonella enterica and Enterobacter spp. carry mcr variants with arnBCADTEF induction. Therapeutic options include adjunct strategies such as antimicrobial peptides, nanomaterials, therapeutic adjuvants, CRISPR-Cas9-based gene editing, probiotics, vaccines, and immune modulators to restore susceptibility. This review identified that specific and wide actions are required to handle the growing colistin resistance, including genomic surveillance, tracing novel resistance mechanisms, and the application of alternative management strategies. The One Health approach is considered a key strategy to address this growing issue. {\textcopyright} 2026 by the authors.",

keywords = "colistin resistance, Gram-negative bacteria, intervention strategies, mcr genes, One Health approach",

author = "Shah Zeb and Arzoo Nazir and Hameed, \{Muhammad Fazal\} and Sadia Ikram and \{Haider Naqvi\}, \{Syed Zeeshan\} and Muhammad Shoaib and Patrick Butaye and Zhiqiang Wang and Ruichao Li and Xiaoyu Lu",

year = "2026",

month = jan,

doi = "10.3390/microorganisms14010173",

language = "English",

volume = "14",

number = "1",

}

TY - JOUR

T1 - Colistin Resistance in Gram-Negative Bacteria

T2 - Mechanisms, Transmission, and Novel Intervention Strategies

AU - Zeb, Shah

AU - Nazir, Arzoo

AU - Hameed, Muhammad Fazal

AU - Ikram, Sadia

AU - Haider Naqvi, Syed Zeeshan

AU - Shoaib, Muhammad

AU - Butaye, Patrick

AU - Wang, Zhiqiang

AU - Li, Ruichao

AU - Lu, Xiaoyu

PY - 2026/1

Y1 - 2026/1

N2 - Multidrug resistance (MDR) in Gram-negative bacteria is a global issue and needs to be addressed urgently. MDR can emerge through genetic mutations and horizontal gene transfer and deteriorate under antibiotic selective pressure. The emergence of resistance to last-resort antibiotics, which are used to treat MDR bacteria, is of particular concern. Colistin has been recognized as a last-line antibiotic for the treatment of MDR Gram-negative bacterial infections caused by Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Recently, the increasing reports of colistin resistance pose a significant threat to public health, caused by both acquired and intrinsic mechanisms. The review aimed to elucidate the trends in colistin resistance, the use of colistin in human and veterinary medicine, underlying resistance mechanisms and transmission pathways, and potential mitigation of this emerging threat through novel intervention strategies. Colistin resistance is mediated by plasmid-encoded phosphoethanolamine transferases (mcr-1 to mcr-10) and chromosomal lipid A remodeling pathways. In Escherichia coli, resistance involves mcr-1–10, acrB efflux mutations, pmrA/pmrB, arnBCADTEF, and mgrB inactivation. Klebsiella pneumoniae exhibits mcr-1, mcr-8, mcr-9, mgrB disruption and phoP/phoQ–pmrAB activation. Acinetobacter baumannii harbors mcr-1–4, while Salmonella enterica and Enterobacter spp. carry mcr variants with arnBCADTEF induction. Therapeutic options include adjunct strategies such as antimicrobial peptides, nanomaterials, therapeutic adjuvants, CRISPR-Cas9-based gene editing, probiotics, vaccines, and immune modulators to restore susceptibility. This review identified that specific and wide actions are required to handle the growing colistin resistance, including genomic surveillance, tracing novel resistance mechanisms, and the application of alternative management strategies. The One Health approach is considered a key strategy to address this growing issue. © 2026 by the authors.

AB - Multidrug resistance (MDR) in Gram-negative bacteria is a global issue and needs to be addressed urgently. MDR can emerge through genetic mutations and horizontal gene transfer and deteriorate under antibiotic selective pressure. The emergence of resistance to last-resort antibiotics, which are used to treat MDR bacteria, is of particular concern. Colistin has been recognized as a last-line antibiotic for the treatment of MDR Gram-negative bacterial infections caused by Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Recently, the increasing reports of colistin resistance pose a significant threat to public health, caused by both acquired and intrinsic mechanisms. The review aimed to elucidate the trends in colistin resistance, the use of colistin in human and veterinary medicine, underlying resistance mechanisms and transmission pathways, and potential mitigation of this emerging threat through novel intervention strategies. Colistin resistance is mediated by plasmid-encoded phosphoethanolamine transferases (mcr-1 to mcr-10) and chromosomal lipid A remodeling pathways. In Escherichia coli, resistance involves mcr-1–10, acrB efflux mutations, pmrA/pmrB, arnBCADTEF, and mgrB inactivation. Klebsiella pneumoniae exhibits mcr-1, mcr-8, mcr-9, mgrB disruption and phoP/phoQ–pmrAB activation. Acinetobacter baumannii harbors mcr-1–4, while Salmonella enterica and Enterobacter spp. carry mcr variants with arnBCADTEF induction. Therapeutic options include adjunct strategies such as antimicrobial peptides, nanomaterials, therapeutic adjuvants, CRISPR-Cas9-based gene editing, probiotics, vaccines, and immune modulators to restore susceptibility. This review identified that specific and wide actions are required to handle the growing colistin resistance, including genomic surveillance, tracing novel resistance mechanisms, and the application of alternative management strategies. The One Health approach is considered a key strategy to address this growing issue. © 2026 by the authors.

KW - colistin resistance

KW - Gram-negative bacteria

KW - intervention strategies

KW - mcr genes

KW - One Health approach

UR - https://www.scopus.com/pages/publications/105029078351

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-105029078351&origin=recordpage

U2 - 10.3390/microorganisms14010173

DO - 10.3390/microorganisms14010173

M3 - RGC 21 - Publication in refereed journal

SN - 2076-2607

VL - 14

JO - Microorganisms

JF - Microorganisms

IS - 1

M1 - 173

ER -

Colistin Resistance in Gram-Negative Bacteria: Mechanisms, Transmission, and Novel Intervention Strategies

Abstract

Funding

UN SDGs

Research Keywords

Publisher's Copyright Statement

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Cite this