Linezolid-resistant Enterococcus faecium clinical isolates from Pakistan: a genomic analysis

Area of Science:

• Microbiology
• Genomics
• Infectious Diseases

Background:

• Linezolid-resistant Enterococcus faecium (LRE) is a critical global pathogen.
• Thirteen LRE isolates were identified in Karachi, Pakistan, between November 2021 and April 2023.
• Investigating strain types and resistance mechanisms is crucial for understanding LRE spread.

Purpose of the Study:

• To characterize the strain types of LRE isolates from Pakistan.
• To identify the molecular mechanisms conferring linezolid resistance in these isolates.
• To provide insights into the epidemiology of LRE in the region.

Main Methods:

• Whole genome sequencing (WGS) was employed for comprehensive genomic analysis.
• Multilocus sequence typing (MLST) was used to determine the clonal complex and sequence types.
• ResFinder and LRE-finder tools identified specific linezolid resistance genes and mutations.

Main Results:

• Twelve of the thirteen LRE isolates belonged to clonal complex 17 (CC17), including ST80, ST612, and ST1380.
• Six isolates harbored the optrA gene and G2576T mutations in the 23S rRNA gene.
• Six isolates carried the poxtA and cfr(D) genes, with one isolate exhibiting all three resistance determinants.

Conclusions:

• The study confirms the prevalence of CC17 sequence types, known for their outbreak potential, in Pakistan.
• Novel molecular mechanisms of linezolid resistance, including combinations of optrA, cfr(D), and poxtA, were identified.
• These findings represent the first report of these specific resistance mechanisms in LRE from Pakistan.