Genomics Insight into cfr-Mediated Linezolid-Resistant LA-MRSA in Italian Pig Holdings

Area of Science:

• Microbiology
• Genomics
• Antimicrobial Resistance

Background:

• The cfr gene confers resistance to multiple antibiotic classes, including phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A.
• cfr genes have been identified in staphylococci, notably methicillin-resistant Staphylococcus aureus (MRSA).
• Livestock-associated MRSA (LA-MRSA) poses a significant public health concern due to its zoonotic potential.

Purpose of the Study:

• To perform in-depth genomic characterization of cfr-positive, multidrug-resistant (MDR) livestock-associated (LA) MRSA clonal complexes (CCs) from Italian pig holdings.
• To investigate the genetic context and location of the cfr gene in these isolates.
• To determine the historical presence of cfr in Italian LA-MRSA strains.

Main Methods:

• Retrospective analysis of three cfr-positive LA-MRSA isolates from Italian pig holdings (2008-2011).
• Combined Illumina and Oxford Nanopore Technologies (ONT) whole genome sequencing (WGS) for genomic characterization.
• Phenotypic testing for linezolid resistance.

Main Results:

• Identified different cfr variants across the three isolates, with only one exhibiting linezolid resistance.
• In one isolate (2008 CC1), the cfr gene was found on a novel plasmid within a Tn558-like transposon.
• In another isolate (2010 CC398), the cfr gene was chromosomally located.
• This study backdates the presence of cfr in Italian LA-MRSA to at least 2008.

Conclusions:

• The findings highlight the genetic diversity of cfr in LA-MRSA and its mobile genetic elements.
• Continuous genomic surveillance of cfr-positive zoonotic LA-MRSA is crucial for public health.
• The early detection of cfr in Italian pigs underscores the importance of monitoring antimicrobial resistance in livestock.