Antibiotics | Understanding Colistin Resistance Mechanisms and Clinical Management Strategies

This article systematically reviews the molecular mechanisms of colistin resistance, analyzes the global epidemiological characteristics of the MCR gene family, and proposes novel diagnostic and therapeutic strategies based on genomics and synthetic biology, providing important theoretical foundations for combating drug-resistant bacteria.

 

Literature Overview
This article, titled 'Understanding Recent Developments in Colistin Resistance: Mechanisms, Clinical Implications, and Future Perspectives', was published in the journal Antibiotics. It reviews and summarizes recent advances in colistin resistance research, including the discovery and spread of the MCR resistance gene, the impact of drug-resistant strains on clinical treatment, and the epidemiological characteristics of resistance genes across different countries and regions. The article also discusses potential future therapeutic strategies.

Background Knowledge
Colistin (including colistin B and colistin E/colistin) is a last-line defense against multidrug-resistant Gram-negative bacteria (MDR GNB). Resistance is primarily mediated by chromosome-encoded lipopolysaccharide (LPS) modifications and the MCR gene family transmitted via plasmids. The MCR-1 to MCR-10 genes modify bacterial outer membrane structures by encoding phosphoethanolamine transferase, reducing colistin binding efficiency and leading to treatment failure and increased mortality. Current detection of drug-resistant strains still faces technical challenges, and the development of rapid diagnostic tools is critical for controlling their spread. In addition, global antimicrobial resistance monitoring systems are not yet fully established, particularly in resource-limited settings. Improving the sensitivity and specificity of resistance detection remains a research focus. Advances in genomics, bioinformatics, and CRISPR technology have provided new tools for studying resistance mechanisms, yet translating these technologies into clinically applicable diagnostic tools remains a challenge.

 

 

Research Methods and Experiments
This article systematically reviews the mechanisms of colistin resistance, including lipopolysaccharide modification, the spread of the MCR gene family, and its epidemiological characteristics across different countries and regions. It also evaluates the limitations of current resistance detection methods and explores the potential applications of genomics, proteomics, and rapid detection technologies in resistance research. By compiling resistance data from multiple countries, the study analyzes the geographical distribution of colistin resistance and its association with antimicrobial usage.

Key Conclusions and Perspectives

• The MCR-1 to MCR-10 gene family has spread globally, with particularly high resistance rates observed in China, India, parts of South America, and Africa.
• Modification of lipopolysaccharide structures (e.g., addition of L-Ara4N and pEtN), mediated by chromosome-encoded PmrAB and PhoPQ systems or plasmid-borne MCR genes, represents the primary mechanism of colistin resistance.
• Colistin resistance leads to clinical treatment failure, prolonged hospital stays, and increased mortality, particularly in infections caused by K. pneumoniae and A. baumannii.
• Current resistance detection methods (e.g., MIC testing, PCR, WGS) face challenges such as high cost, low sensitivity, and complex operation in resource-limited areas.
• Whole-genome sequencing (WGS) and bioinformatics analysis play a significant role in uncovering resistance gene variations and novel resistance mechanisms, but are not yet widely implemented in routine clinical diagnostics.
• Combination therapies involving colistin (e.g., with carbapenems, rifampin, or tigecycline) have shown improved clinical cure rates and microbial clearance in some studies, though further clinical validation is required.
• New therapeutic approaches based on CRISPR gene editing, phage therapy, and nanotechnology are being explored to enhance the clinical efficacy of colistin and reduce resistance transmission.

Research Significance and Prospects
This review highlights the urgency of colistin resistance on a global scale and emphasizes the need to strengthen resistance monitoring, optimize antimicrobial stewardship, develop novel rapid diagnostic tools, and explore alternative therapies. Future research should focus on molecular dissection of resistance mechanisms, development of rapid resistance detection methods, and strategies for reversing resistance using synthetic biology and gene editing technologies. Implementation of the global One Health strategy will help integrate human, animal, and environmental resistance data, providing systematic solutions for colistin resistance prevention and control.

 

 

Conclusion
The rapid spread of colistin resistance has become a significant threat to global public health, particularly in the treatment of multidrug-resistant bacterial infections. This article systematically analyzes resistance mechanisms, clinical impacts, and global resistance distribution, highlighting that horizontal transmission of the MCR gene family and chromosomal mutations lead to treatment failure and increased mortality. Future research should integrate genomics, synthetic biology, and CRISPR platforms to develop more efficient diagnostic and therapeutic strategies. Additionally, improvements in global antimicrobial stewardship policies, resistance monitoring systems, and collaboration among clinical, research, and industrial sectors will be crucial for delaying resistance spread and preserving the clinical efficacy of colistin.

 

Shreya Singh, Rajesh Kumar Sahoo, and Mahesh Chandra Sahu. Understanding Recent Developments in Colistin Resistance: Mechanisms, Clinical Implications, and Future Perspectives. Antibiotics.