The pan-genome of the emerging multidrug-resistant pathogen Corynebacterium striatum

Abstract

Corynebacterium striatum, a common constituent of the human skin microbiome, is now considered an emerging multidrug-resistant pathogen of immunocompromised and chronically ill patients. However, little is known about the molecular mechanisms in the transition from colonization to the multidrugresistant (MDR) invasive phenotype in clinical isolates. This study performed a comprehensive pangenomic analysis of C. striatum, including isolates from 'normal skin microbiome' and from MDR infections, to gain insights into genetic factors contributing to pathogenicity and multidrug resistance in this species. For this, three novel genome sequences were obtained from clinical isolates of C. striatum of patients from Brazil, and other 24 complete or draft C. striatum genomes were retrieved from GenBank, including the ATCC6940 isolate from the Human Microbiome Project. Analysis of C. striatum strains demonstrated the presence of an open pan-genome (α = 0.852803) containing 3,816 gene families, including 15 antimicrobial resistance (AMR) genes and 32 putative virulence factors. The core and accessory genomes included 1,297 and 1,307 genes, respectively. The identi ed AMR genes are primarily associated with resistance to aminoglycosides and tetracyclines. Of these, 66.6% are present in genomic islands, and four AMR genes, including aac(6')-ib7, are located in a class 1-integron. In conclusion, our data indicated that C. striatum possesses genomic characteristics favorable to the invasive phenotype, with high genomic plasticity, a robust genetic arsenal for iron acquisition, and important virulence determinants and AMR genes present in mobile genetic elements.

The Pan-Genomic Analysis of Corynebacterium striatum Revealed its Genetic Characteristics as an Emerging Multidrug-Resistant Pathogen

“…In this study, we performed a pan-genomic analysis of 314 genomes of C. striatum , revealing an open pan-genome composed of 5692 gene families. This result is consistent with the findings of Jesus et al, 28 but our study used a larger number of strains and identified more gene families. Through KEGG pathway annotation of gene families, we observed that the majority of the genes were associated with transcription and metabolism, while accessory genes and unique genes composed pathways such as Cellular community, Circulatory system, Environmental adaptation, and Immune system.…”

“…However, the positions of less-studied genes, such as APH (6), APH(3'), and ANT(3"), within the C. striatum genome have not been established. In contrast to the study by Jesus et al, 28 our research used a larger dataset, which allowed us to identify additional genes, including the new gene family ANT (3''). This family encodes aminoglycoside O-nucleotide transferases that transfer the AMP group from the ATP substrate to the 3″-hydroxyl group of the compound, resulting in the inactivation of aminoglycoside antibiotics.…”

“…A total of 298 genome sequences and 72 Whole genome sequencing (WGS) data of C. striatum were selected for this study from the National Center for Biotechnology Information (NCBI) database (ftp://ftp.ncbi.nlm.nih.gov), based on studies by other reaches. 13,[28][29][30][31][32][33][34][35][36] The phenotypic information of each strain was obtained by searching the NCBI BioSample database and papers, such as host, geographical locations, isolated tissue, disease, etc. In order to ensure the availability of data, we only retained strains with known geographical locations and isolation tissues, and removed 14 strains with incomplete information.…”

“…27 However, there are few studies on the pan-genomic analysis of C. striatum to investigate its population diversity and evolutionary relationships, as well as the distribution of drug resistance genes and virulence factors within its population. Only one study 28 has analyzed 30 genomes of C. striatum, but the limited number of strains used in that study does not provide a representative sample of the entire population. Therefore, this study obtained whole-genome sequencing data and phenotypic information for all available C. striatum strains from public databases.…”

Species- and strain-level diversity of Corynebacteria isolated from human facial skin

“…The C. pseudokroppenstedtii strain P15-C1 was resistant to multiple antibiotics, including penicillin, clindamycin and ciprofloxacin. Similar multi-resistance phenotypes were previously predicted in specific strains of C. accolens and C. striatum [ 39 – 41 ]. The resistance genes ( erm X, aph (3’), aph (3’’), aph (6) and a gene encoding an MFS efflux pump, predicted to be responsible for chloramphenicol resistance) were clustered in a 17 kb region that seems to be a region of high genome plasticity, since it harbors multiple repeats (five 841 bp repeats) and nine genes encoding mobile elements proteins or derivatives thereof (IS6, IS3 and Tn3 family transposases).…”