Multiple mutations in lipid-A modification pathway & novel fosA variants in colistin-resistant Klebsiella pneumoniae

Area of Science:

• Microbiology
• Genomics
• Antimicrobial Resistance

Background:

• Colistin is a critical antibiotic for treating multidrug-resistant Gram-negative infections.
• Klebsiella pneumoniae is a major opportunistic pathogen frequently associated with healthcare-associated infections.
• Emergence of colistin resistance in K. pneumoniae poses a significant threat to public health.

Purpose of the Study:

• To investigate the molecular mechanisms underlying colistin resistance in a cluster of Klebsiella pneumoniae isolates.
• To identify specific genetic mutations and pathways involved in conferring resistance.
• To determine the absence of mcr genes in the studied isolates.

Main Methods:

• Antimicrobial susceptibility testing using disk diffusion and broth microdilution.
• Whole-genome sequencing (WGS) for comprehensive genetic analysis.
• Bioinformatic analysis of WGS data to identify mutations in resistance-associated genes.

Main Results:

• Eight colistin-resistant K. pneumoniae isolates were identified, belonging to three distinct sequence types (ST11, ST14, ST231).
• Novel and rare mutations were found in the eptA and arnT genes, involved in the lipopolysaccharide modification pathway.
• Substitutions were also observed in mgrB, pmrB, phoP, and phoQ genes, while mcr genes were absent.
• Variants in existing classes of the fosA gene were detected.

Conclusions:

• The colistin resistance in these K. pneumoniae isolates is likely due to a complex interplay of mutations in multiple genes.
• The absence of mcr genes highlights the importance of alternative resistance mechanisms.
• Continuous molecular surveillance is crucial for understanding and combating the spread of colistin resistance.