Antibiotic resistance profiles of seven genomospecies of Corynebacterium jeikeium analyzed by whole genome sequencing.

Corynebacterium jeikeium is an opportunistic human pathogen with high genomic diversity. In the past, multi-drug resistance has been considered a hallmark of C. jeikeium. However, some strains of C. jeikeium are fully susceptible and thus, their reclassification would avoid the empirical therapy with glycopeptides. One hundred eighty-six clinical isolates and four reference isolates identified as C. jeikeium between 1994-1999 and 2012-2019, respectively, were analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and 16S ribosomal RNA (16S rRNA) gene sequence analysis. A total of 153 confirmed C. jeikeium isolates was further analyzed by whole genome sequencing (WGS) and by disk diffusion antimicrobial susceptibility testing (AST). WGS and subsequent core genome single nucleotide polymorphism-based phylogenetic analysis segregated the isolates into seven phylogenetic clusters. The average nucleotide identity between the clusters was <95%, qualifying them as separate C. jeikeium genomospecies. Overall, AST profiles of all 153 isolates were heterogeneous for six of the 16 antibiotics tested. Notably, genomospecies 6 and 7 displayed mainly comparably small inhibition zones. For the other 10 antibiotics, all genomospecies displayed either small or large inhibition zones, respectively. Our study of C. jeikeium clinical isolates revealed a relatively complex phylogenetic structure. As soon as clear phenotypic traits can be attributed to the seven genomospecies by routine diagnostic tests, genomospecies encompassing mainly antibiotic-susceptible strains should be reclassified to fine-tune potential treatment strategies.IMPORTANCECorynebacterium jeikeium isolates typically display multi-drug resistance (MDR), frequently triggering empirical therapies with glycopeptides. However, some strains are susceptible to a broad range of antibiotics. In our study, analysis of a large collection of C. jeikeium by whole genome sequencing (WGS) and antibiotic resistance testing revealed genomic diversity, and some correlations between MDR phenotypes and specific genomospecies. While WGS is not yet a routine method, identification of MDR genomospecies may confirm the need for glycopeptide therapy. Identification of a less-resistant genomospecies would have even a higher clinical impact, as unnecessary therapies with glycopeptides are avoided, thereby reducing the selection for vancomycin-resistant enterococci. In the future, databases of diagnostic tools, e.g., MALDI-TOF, may be expanded to allow for the differentiation of genomospecies. Furthermore, rational taxonomic reclassification of some C. jeikeium genomospecies would help clinicians to fine-tune potential treatment strategies.