Corynebacterium diphtheriae is one of the most prominent human pathogens and the causative agent of the communicable disease diphtheria. The genomes of 12 strains isolated from patients with classical diphtheria, endocarditis, and pneumonia were completely sequenced and annotated. Including the genome of C. diphtheriae NCTC 13129, we herewith present a comprehensive comparative analysis of 13 strains and the first characterization of the pangenome of the species C. diphtheriae . Comparative genomics showed extensive synteny and revealed a core genome consisting of 1,632 conserved genes. The pangenome currently comprises 4,786 protein-coding regions and increases at an average of 65 unique genes per newly sequenced strain. Analysis of prophages carrying the diphtheria toxin gene tox revealed that the toxoid vaccine producer C. diphtheriae Park-Williams no. 8 has been lysogenized by two copies of the ω tox + phage, whereas C. diphtheriae 31A harbors a hitherto-unknown tox + corynephage. DNA binding sites of the tox -controlling regulator DtxR were detected by genome-wide motif searches. Comparative content analysis showed that the DtxR regulons exhibit marked differences due to gene gain, gene loss, partial gene deletion, and DtxR binding site depletion. Most predicted pathogenicity islands of C. diphtheriae revealed characteristics of horizontal gene transfer. The majority of these islands encode subunits of adhesive pili, which can play important roles in adhesion of C. diphtheriae to different host tissues. All sequenced isolates contain at least two pilus gene clusters. It appears that variation in the distributed genome is a common strategy of C. diphtheriae to establish differences in host-pathogen interactions.

SUMMARYPhenotypic characteristics, antimicrobial susceptibility profile, and clinical-epidemiological features of 28 Nocardia strains isolated from 19 cases of bovine mastitis, eight cutaneous-subcutaneous lesions and one case of pneumonia in dogs were evaluated. Microbiological, biochemical, cytological and scanning electron microscopy methods were used in diagnosis. Nocardia asteroides type IV, Nocardia otitidiscaviarum, Nocardia nova (type III) and Nocardia farcinica (type V) were isolated from bovine milk, bronchial lavage and/or cutaneous-subcutaneous abscesses in dogs. Nocardial bovine mastitis was diagnosed predominantly in clinical cases, in dairy herds with poor environmental hygienic conditions between milking and inappropriate intramammary therapy. Canine nocardiosis was observed commonly in animals co-infected with distemper virus. Sulphamethoxazole-trimethoprim (92.8%), amikacin (92.8%) and ceftiofur (92.8%) were the most effective drugs in 28 isolates. Multiple drug resistance to three or more and five or more antimicrobials was observed in ten (35.7%) and three (10.7%) strains, respectively, predominantly with use of cloxaxillin, cefoperazone and ampicillin. The species (type) classification, clinical-epidemiological characteristics, diagnosis, multiple drug resistance and public health considerations in Nocardia strains isolated from cattle and dogs in Brazil are discussed, with special reference to report of bovine mastitis by N. otitidiscaviarum by first time in Brazil and the similarity between Nocardia species isolated from human and animal origin.

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Over a five-year period, 163 strains of Corynebacterium sp. were recovered from different clinical specimens of patients from a Brazilian University hospital. Genitourinary tract and intravenous sites specimens were the most frequent sources of corynebacteria (46.62%). Corynebacterium amycolatum (29.55%), Corynebacterium minutissimum (20.45%) and Corynebacterium pseudodiphtheriticum (13.63%) were the predominant species found in genitourinary tract. C. minutissimum (24.14%) and Corynebacterium propinquum (17.24%) in surgical and/or other skin wounds and abscesses; Corynebacterium xerosis (25%), C. amycolatum (21.87%) and C. pseudodiphtheriticum (18.75%) in intravenous sites; C. pseudodiphtheriticum (33.33%) and C. propinquum (33.33%) in lower respiratory tract. Microorganisms were all susceptible to vancomycin and most of the species was predominantly resistant to β-lactams. Antimicrobial susceptibility patterns of corynebacteria were not predictable. Multiple antibiotic resistance observed in C. jeikeium was also found among C. xerosis, C. minutissimum, C. afermentans, C. propinquum, C. amycolatum and C. pseudodiphtheriticum strains. Data suggest awareness of clinicians and microbiologists to nosocomial infections especially due to antimicrobial multiresistant strains of Corynebacterium sp.

At two main teaching hospitals in Brazil, Streptococcus spp. was the principal pathogen of CAIE while S. aureus and Enterococcus spp. were the most frequent causes of HAIE. IE remains a serious disease associated with high in-hospital mortality rate (46.6%); especially, in individuals over 45 years of age and with renal failure. Data suggest that early surgery may improve the outcome of IE patients.