The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence

Abstract

BackgroundCorynebacterium pseudotuberculosis is generally regarded as an important animal pathogen that rarely infects humans. Clinical strains are occasionally recovered from human cases of lymphadenitis, such as C. pseudotuberculosis FRC41 that was isolated from the inguinal lymph node of a 12-year-old girl with necrotizing lymphadenitis. To detect potential virulence factors and corresponding gene-regulatory networks in this human isolate, the genome sequence of C. pseudotuberculosis FCR41 was determined by pyrosequencing and functionally annotated.ResultsSequencing and assembly of the C. pseudotuberculosis FRC41 genome yielded a circular chromosome with a size of 2,337,913 bp and a mean G+C content of 52.2%. Specific gene sets associated with iron and zinc homeostasis were detected among the 2,110 predicted protein-coding regions and integrated into a gene-regulatory network that is linked with both the central metabolism and the oxidative stress response of FRC41. Two gene clusters encode proteins involved in the sortase-mediated polymerization of adhesive pili that can probably mediate the adherence to host tissue to facilitate additional ligand-receptor interactions and the delivery of virulence factors. The prominent virulence factors phospholipase D (Pld) and corynebacterial protease CP40 are encoded in the genome of this human isolate. The genome annotation revealed additional serine proteases, neuraminidase H, nitric oxide reductase, an invasion-associated protein, and acyl-CoA carboxylase subunits involved in mycolic acid biosynthesis as potential virulence factors. The cAMP-sensing transcription regulator GlxR plays a key role in controlling the expression of several genes contributing to virulence.ConclusionThe functional data deduced from the genome sequencing and the extended knowledge of virulence factors indicate that the human isolate C. pseudotuberculosis FRC41 is equipped with a distinct gene set promoting its survival under unfavorable environmental conditions encountered in the mammalian host.

Transcription of Sialic Acid Catabolism Genes in Corynebacterium glutamicum Is Subject to Catabolite Repression and Control by the Transcriptional Repressor NanR

“…S10 in the supplemental material). Similar to the case with C. glutamicum, the genes encoding the putative Neu5Ac uptake systems are located in the genomes of C. diphtheriae (strain INCA 402), C. ulcerans (strain 809), and C. pseudotuberculosis (strain FRC41) adjacent to the gene for the corresponding transcriptional regulator, separated by a short intergenic region (86)(87)(88). In analyses of the genome sequences using FIMO and the consensus motif for C. glutamicum NanR-binding sites, we were able to identify highly conserved 21-bp motifs within the intergenic regions of these related species (see Fig.…”

The two-component system ChrSA is crucial for haem tolerance and interferes with HrrSA in haem-dependent gene regulation in Corynebacterium glutamicum

“…Variations in the regulatory network composition in these closely related species may be surprising; however, sequence analysis revealed striking differences between Corynebacterium species regarding their TCS equipment (Bott & Brocker, 2012). With respect to HrrSA and ChrSA, several corynebacterial genomes contain only one of the two systems; both systems together were identified in the C. glutamicum species C. diphtheriae, C. pseudotuberculosis and C. lipophiloflavum (Bott & Brocker, 2012;Cerdeño-Tárraga et al, 2003;Kalinowski et al, 2003;Trost et al, 2010;Yukawa et al, 2007). These findings indicate significant variation at the species level and suggest an individual network constitution meeting the requirements of each particular species.…”

Pangenomic Study of Corynebacterium diphtheriae That Provides Insights into the Genomic Diversity of Pathogenic Isolates from Cases of Classical Diphtheria, Endocarditis, and Pneumonia

“…The purification of chromosomal DNA from C. diphtheriae was performed as described previously (80). Briefly, 50-ml aliquots of bacterial cultures grown for 48 to 72 h in BHI broth were centrifuged at 4°C and 2,000 ϫ g for 20 min.…”