학술논문

Biofilm regulation in Clostridioides difficile: Novel systems linked to hypervirulence.
Document Type
Article
Source
PLoS Pathogens. 9/9/2021, Vol. 17 Issue 9, p1-20. 20p.
Subject
*CLOSTRIDIOIDES difficile
*BIOFILMS
*ANTIBIOTICS
*BACTERIAL adhesion
*ANAEROBIC bacteria
*QUORUM sensing
*EXTRACELLULAR matrix proteins
*GENETIC regulation
Language
ISSN
1553-7366
Abstract
Clostridiodes difficile (C. difficile) was ranked an "urgent threat" by the Centers for Disease Control and Prevention (CDC) in 2019. C. difficile infection (CDI) is the most common healthcare-associated infection (HAI) in the United States of America as well as the leading cause of antibiotic-associated gastrointestinal disease. C. difficile is a gram-positive, rod-shaped, spore-forming, anaerobic bacterium that causes infection of the epithelial lining of the gut. CDI occurs most commonly after disruption of the human gut microflora following the prolonged use of broad-spectrum antibiotics. However, the recurrent nature of this disease has led to the hypothesis that biofilm formation may play a role in its pathogenesis. Biofilms are sessile communities of bacteria protected from extracellular stresses by a matrix of self-produced proteins, polysaccharides, and extracellular DNA. Biofilm regulation in C. difficile is still incompletely understood, and its role in disease recurrence has yet to be fully elucidated. However, many factors have been found to influence biofilm formation in C. difficile, including motility, adhesion, and hydrophobicity of the bacterial cells. Small changes in one of these systems can greatly influence biofilm formation. Therefore, the biofilm regulatory system would need to coordinate all these systems to create optimal biofilm-forming physiology under appropriate environmental conditions. The coordination of these systems is complex and multifactorial, and any analysis must take into consideration the influences of the stress response, quorum sensing (QS), and gene regulation by second messenger molecule cyclic diguanosine monophosphate (c-di-GMP). However, the differences in biofilm-forming ability between C. difficile strains such as 630 and the "hypervirulent" strain, R20291, make it difficult to assign a "one size fits all" mechanism to biofilm regulation in C. difficile. This review seeks to consolidate published data regarding the regulation of C. difficile biofilms in order to identify gaps in knowledge and propose directions for future study. Author summary: Clostridioides difficile (C. difficile) is an opportunistic bacterial pathogen that causes infection of the human gut epithelium following disruption of the normal gut microflora, usually by broad-spectrum antibiotics. C. difficile infection (CDI) is recurrent in 20% to 30% of cases and can lead to significant health-related complications such as pseudomembranous colitis and, in severe cases, death. The impact and cost of this pathogen on healthcare systems are significant, and some aspects of the pathogen's lifestyle in the host are, as yet, unknown. It is hypothesised that C. difficile exists in the gut as a biofilm due to the infection's severity and recurrent nature. The biofilm mode of bacterial growth can protect the cells from external factors such as antibiotic treatment, physiological processes, and the immune system. However, biofilm regulation in C. difficile is not yet fully characterised, and in this review, we consolidate published primary research on C. difficile biofilm regulation to gain a comprehensive overview of the factors involved and how they may interact to enable biofilm development within a host. [ABSTRACT FROM AUTHOR]