RESUMO
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 multidrug-resistant (MDR) invasive phenotype in clinical isolates. This study performed a comprehensive pan-genomic 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 3816 gene families, including 15 antimicrobial resistance (AMR) genes and 32 putative virulence factors. The core and accessory genomes included 1297 and 1307 genes, respectively. The identified 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.
Assuntos
Antibacterianos , Corynebacterium , Humanos , Fenótipo , Fatores de Virulência/genética , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade MicrobianaRESUMO
Corynebacterium diphtheriae still represents a global medical challenge, particularly due to the significant number of individuals susceptible to diphtheria and the emergence of non-toxigenic strains as the causative agents of invasive infections. In this study, we characterized the clinical and microbiological features of what we believe to be the first case of C. diphtheriae infection of a percutaneous nephrostomy catheter insertion site in an elderly patient with a fatal bladder cancer. Moreover, we demonstrated the potential role of adherence, biofilm formation and fibrin deposition traits in C. diphtheriae from the catheter-related infection. Non-toxigenic C. diphtheriae isolated from the purulent discharge (named strain BR-CAT5003748) was identified by the API Coryne system (code 1 010 324) and a multiplex PCR for detection of dtxR and tox genes. Strain BR-CAT5003748 showed resistance to oxacillin, ceftazidime and ciprofloxacin. In experiments performed in vitro, the catheter isolate was classified as moderately hydrophobic and as moderately adherent to polystyrene surfaces. Glass provided a more effective surface for biofilm formation than polystyrene. Micro-organisms adhered to (>1.5 x 10(6) c.f.u.) and multiplied on surfaces of polyurethane catheters. Microcolony formation (a hallmark of biofilm formation) and amorphous accretions were observed by scanning electron microscopy on both external and luminal catheter surfaces. Micro-organisms yielded simultaneous expression of localized adherence-like and aggregative-like (LAL/AAL) adherence patterns to HEp-2 cells. Interestingly, the coagulase tube test resulted in the formation of a thin layer of fibrin embedded in rabbit plasma by the non-toxigenic BR-CAT5003748 strain. In conclusion, C. diphtheriae should be recognized as a potential cause of catheter-related infections in at-risk populations such as elderly and cancer patients. LAL/AAL strains may be associated with virulence traits that enable C. diphtheriae to effectively produce biofilms on catheter surfaces. Biofilm formation and fibrin deposition could have contributed to the persistence of C. diphtheriae at the infected insertion site and the obstruction of the nephrostomy catheter.