Congresso Brasileiro de Microbiologia 2023 | Resumo: 601-2 | ||||
Resumo:The clinical features observed in cases of classic diphtheria caused by Corynebacterium diphtheriae are associated with diphtheria toxin production (DT), its main virulence factor. However, non-DT-producing strains have been isolated from invasive infections. Recent studies have demonstrated the involvement of a multifactorial virulence mechanism expressed by C. diphtheriae strains. The analysis of the pangenome of this species identified the presence of 57 genomic islands, indicating that horizontal gene transfer is a strategy frequently used by corynebacteria to establish differences in pathogen-host interactions. Additionally, genes encoding hemolysins, was also detected in C. diphtheriae strains. It is known that hemolysins is able to cause cell damage through pore formation. Horizontal transfer of hemolysin (hlyA) genes was reported in Escherichia coli and other bacterial species. Some strains of C. diphtheriae are able to produce specific hemolysins, as they are classified according to hemolytic activity. Genomic sequencing of the C. diphtheriae biotype gravis NCTC 13129 strain identified the sequence of a hypothetical hemolysin-like protein (TlyA) from Mycobacterium tuberculosis. Therefore, this study aimed to evaluate the presence and expression of the tlyA-like gene and its role in the virulence of the C. diphtheriae strains. Thus, the following experiments were performed: i) in silico analysis of hemolysin genes; ii) construction of the tlyA- disrupted mutant strain; iii) gene expression analysis by qPCR; iv) hemolytic activity of the wild and mutant strains; v) arthritogenic potential using a murine model. In silico analysis showed that C. diphtheriae strains harbour genes that encode proteins with expressive homology to the tlyA hemolysin. In addition, the mutant strain was unable to express tlyA gene. The disrupting of tlyA gene led to a decrease in arthritogenic potential in murine. Additional studies are necessary to better understand the role of TlyA-like hemolysin in the virulence of C. diphtheriae.
Keywords: Corynebacterium diphtheriae, hemolysin, tlyA gene, virulence.
Development Agency: CNPq, CAPES, FAPERJ, SR-2 UERJ. Palavras-chave: Corynebacterium diphtheriae, hemolysin, tlyA gene, virulence Agência de fomento:CNPq, CAPES, FAPERJ, SR-2 UERJ |