Molecular basis of linezolid resistance in Finegoldia spp. from orthopedic infections

ABSTRACT Finegoldia spp. are Gram-positive anaerobic cocci increasingly recognized as opportunistic pathogens, particularly in bone infections. Linezolid (LZD), an oxazolidinone with activity against anaerobes, is frequently used in orthopedic infections but is subject to various resistance mechanisms. Here, we characterized the molecular basis of LZD resistance in Finegoldia sp. isolates from three separate cases of bone infection. Antimicrobial susceptibility testing (AST) was performed according to Antibiotic Susceptibility Committee of the French Society of Microbiology (CA-SFM) recommendations. Whole-genome sequences were analyzed to challenge mass spectrometry identification (ANIb, is DDH), determine isolate relatedness (SNP analysis), and characterize the genetic support of resistance (ABRicate, AMRFinderPlus). LZD-resistant strains were isolated following LZD treatment in all three patients. In one case, low SNP divergence between susceptible and resistant isolates supported in vivo emergence of resistance. Genomic analyses suggested that the strains probably belong to undescribed Finegoldia species. LZD resistance was mediated by the cfr (C) gene encoding a 23S rRNA methyltransferase, and in two isolates with high-level resistance, was associated with a G71D mutation in the ribosomal protein L4-encoding gene. The cfr (C) gene was located on two distinct integrative and conjugative elements closely related to ones previously described in Clostridioides difficile and Faecalibacterium taiwanense . In anaerobes, LZD resistance remains rarely reported in the literature, except in non- fragilis Bacteroides species. However, LZD resistance in the Finegoldia genus highlighted in this study supports the need for systematic AST of Finegoldia sp. isolates, particularly in polymicrobial infections, when LZD is considered for the treatment. If LZD is ineffective, tedizolid testing may be suggested as a potential therapeutic alternative.