title: Corynebacterium diphtheriae as an emerging pathogen in nephrostomy catheter-related infection: evaluation of traits associated with bacterial virulence.
abstract: 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.
authors.affiliation: Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Débora L R
authors.initials: DLR
authors.lastname: Gomes
authors.affiliation: Hospital Infection Control Committee, National Cancer Institute, INCA, Health Ministry, Rio de Janeiro, RJ, Brazil.|Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos A S
authors.initials: CAS
authors.lastname: Martins
authors.affiliation: Hospital Infection Control Committee, National Cancer Institute, INCA, Health Ministry, Rio de Janeiro, RJ, Brazil.
authors.forename: Lúcia M D
authors.initials: LMD
authors.lastname: Faria
authors.affiliation: Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Louisy S
authors.initials: LS
authors.lastname: Santos
authors.affiliation: Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Cintia S
authors.initials: CS
authors.lastname: Santos
authors.affiliation: Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Priscila S
authors.initials: PS
authors.lastname: Sabbadini
authors.affiliation: Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Mônica C
authors.initials: MC
authors.lastname: Souza
authors.affiliation: Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Gabriela B
authors.initials: GB
authors.lastname: Alves
authors.affiliation: Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Ana C P
authors.initials: ACP
authors.lastname: Rosa
authors.affiliation: Roberto Alcantara Gomes Biology Institute, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Prescilla E
authors.initials: PE
authors.lastname: Nagao
authors.affiliation: Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Pereira
authors.affiliation: Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Raphael
authors.initials: R
authors.lastname: Hirata
authors.affiliation: Laboratory of Diphtheria and Corynebacteria of Medical Relevance, Faculty of Medicine, University of the State of Rio de Janeiro, UERJ, Rio de Janeiro, RJ, Brazil.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Mattos-Guaraldi
mesh_terms: D000368:Aged; D001422:Bacterial Adhesion; D018441:Biofilms / Q000254:growth & development; D055499:Catheter-Related Infections / Q000382:microbiology*; D002408:Catheters, Indwelling / Q000382:microbiology; D002460:Cell Line; D003353:Corynebacterium diphtheriae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D004165:Diphtheria / Q000382:microbiology*; D017809:Fatal Outcome; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D008297:Male; D009403:Nephrostomy, Percutaneous / Q000009:adverse effects*; D011140:Polyurethanes; D001749:Urinary Bladder Neoplasms / Q000628:therapy; D014774:Virulence
chemical_list: D011140:Polyurethanes; D005337:Fibrin