Expression of virulence factors of Clostridioides difficile at sub-minimum inhibitory concentration of antibiotics

Abstract

Clostridioides difficile (C. difficile) generally colonizes in the colon of hospitalized patients who receive antibiotics for a long time. C. difficile expresses its virulence factors which are associated with pathogenesis. Naturally, the expression of these virulence factors may be influenced by antibiotics. The effect of antibiotics at the sub-minimum inhibitory concentration (MIC) on virulence factors has been investigated and it is varied and depends on the type of antibiotic and C. difficile isolate. Some of the antibiotics at sub-MIC upregulate virulence factors, while others downregulate. Meanwhile, some antibiotics have no detectable effects on the regulation of virulence factors. Nearly, all investigations have surveyed a few numbers of C. difficile isolates in terms the expression of virulence factors at sub-MIC. Most of the antibiotics at sub-MICs regulate gene expression of virulence factors, toxin production, spore formation, and germination by several mechanisms especially the SOS response system. However, to achieve a clear understanding of the effect of antibiotics at sub-MIC on the expression of genes of virulence factors, which are related to the pathogenesis of C. difficile, further and wider investigations are needed, especially on the issue of the numbers of isolates that have been discussed in the present review article.