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 (.1.5¾10 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. INTRODUCTIONInfections due to bacteria that form biofilms are a clinical problem (Donlan, 2001;Rao et al., 2008 Non-diphtherial corynebacteria have been reported to be infecting pathogens or copathogens in at-risk populations such as immunocompromised patients and patients with indwelling medical devices (Cavendish et al., 1994;Esteban et al., 1999;Wang et al., 2001;Dobler & Braveny, 2003;Schiffl et al., 2004;Lee et al., 2005;Teixido et al., 2007;Dalal & Likhi, 2008).Corynebacterium diphtheriae infections represent a global medical challenge, particularly due to the significant rise in the percentage of adults susceptible to diphtheria (MattosGuaraldi et al., 2001) and the emergence of non-toxigenic strains as the causative agents of endocarditis and other systemic infections . This pathogen is also becoming successful i...

Fibrinogen binds to nontoxigenic and toxigenic Corynebacterium diphtheriae strains

“…Bacterial interaction with rabbit plasma -Interaction of microorganisms with fresh and sterile EDTA (ethylenediaminetetraacetic sodium salt)-chelated rabbit plasma (Ebe Farma Biológica e Agropecuária) was evaluated by both slide and tube tests based on procedures previously described for S. aureus (Christensen et al 1983, MacFaddin 2000, Gomes et al 2009). Bacterial morphology was checked by staining positive tests with crystal violet.…”

“…However, the association of nontoxigenic strains with localized disease and with cases of invasive infection has become recognized, particularly with endocarditis (Gubler et al 1998, Galazka 2000, Mattos-Guaraldi et al 2000, Kanungo et al 2002, Gomes et al 2009). Various authors share the opinion that nontoxigenic strains may be responsible for pharyngitis and should be treated (Jephcott et al 1975, Wilson 1995, Rakhmanova et al 1997, Bonnet & Begg 1999.…”

“…Various authors share the opinion that nontoxigenic strains may be responsible for pharyngitis and should be treated (Jephcott et al 1975, Wilson 1995, Rakhmanova et al 1997, Bonnet & Begg 1999. However, it is also emphasized that additional studies are still required to obtain more complete information on the pathogenicity or copathogenicity of nontoxigenic C. diphtheriae associated with cases of infection in the respiratory tract (Reacher et al 2000, Gomes et al 2009.…”

Reannotation of the Corynebacterium diphtheriae NCTC13129 genome as a new approach to studying gene targets connected to virulence and pathogenicity in diphtheria

“…After a huge effort from the health organizations to contain the disease, the immunization coverage has reached approximately 82% of the world population in 2009, decreasing the number of reported cases to 857 in the same year (World Health Organization). However, the identification of nontoxigenic C. diphtheriae strains, ie, strains unable to produce the diphtheria toxin, which have caused invasive diseases, such as endocarditis, 11,12 has to be treated as a new potential problem in public health.Therefore, it has become highly relevant to improve and update the already existing data about this pathogen, with the goal of increasing genetic knowledge linked to its genome and to propose new approaches and precise diagnostics that will prevent or minimize the effects of its resurgence. The reannotated file can be downloaded freely through the authors' server, at: http://lgcm.icb.ufmg.br/pub/C_diphtheriae_reannotation.embl.…”

“…After a huge effort from the health organizations to contain the disease, the immunization coverage has reached approximately 82% of the world population in 2009, decreasing the number of reported cases to 857 in the same year (World Health Organization). However, the identification of nontoxigenic C. diphtheriae strains, ie, strains unable to produce the diphtheria toxin, which have caused invasive diseases, such as endocarditis, 11,12 has to be treated as a new potential problem in public health.…”