Tag Archives: ASM

Study Hypothesized Commensal Clostridia are Important for Providing Colonization Resistance Against C. difficile Due to Their Ability to Produce Secondary Bile Acids

ABSTRACT

Clostridioides difficile is one of the leading causes of antibiotic-associated diarrhea.

Gut microbiota-derived secondary bile acids and commensal Clostridia that carry the bile acid-inducible (bai) operon are associated with protection from C. difficile infection (CDI), although the mechanism is not known.

In this study, we hypothesized that commensal Clostridia are important for providing colonization resistance against C. difficile due to their ability to produce secondary bile acids, as well as potentially competing against C. difficile for similar nutrients.

To test this hypothesis, we examined the abilities of four commensal Clostridia carrying the bai operon (Clostridium scindens VPI 12708, C. scindens ATCC 35704, Clostridium hiranonis, and Clostridium hylemonae) to convert cholate (CA) to deoxycholate (DCA) in vitro, and we determined whether the amount of DCA produced was sufficient to inhibit the growth of a clinically relevant C. difficile strain.

We also investigated the competitive relationships between these commensals and
C. difficile using an in vitro coculture system.

We found that inhibition of C. difficile growth by commensal Clostridia supplemented with CA was strain dependent, correlated with the production of ∼2 mM  DCA, and increased the expression of bai operon genes.

We also found that C. difficile was able to outcompete all four commensal Clostridia in an in vitro coculture system. These studies are instrumental in understanding the relationship between commensal Clostridia and C. difficile in the gut, which is vital for designing targeted bacterial therapeutics. Future studies dissecting the regulation of the bai operon in vitro and in vivo and how this affects CDI will be important.

IMPORTANCE : Commensal Clostridia carrying the bai operon, such as C. scindens, have been associated with protection against CDI; however, the mechanism for this protection is unknown. Herein, we show four commensal Clostridia that carry the bai operon and affect                                C. difficile growth in a strain-dependent manner, with and without the addition of cholate. Inhibition of C. difficile by commensals correlated with the efficient conversion of cholate to deoxycholate, a secondary bile acid that inhibits C. difficile germination, growth, and toxin production.

Competition studies also revealed that C. difficile was able to outcompete the commensals in an in vitro coculture system.

These studies are instrumental in understanding the relationship between commensal Clostridia and C. difficile in the gut, which is vital for designing targeted bacterial therapeutics.

 

 

 

 

 

 

SOURCE: https://jb.asm.org/content/202/11/e00039-20

Clostidium difficile Most Recent Research Discussed By ASM and Dr. Alice Guh, MD, MPH of the CDC

Clostridium difficile is an increasingly important problem being faced by clinical microbiologists. From 1993 to 2009, incidence of C. difficile increased fourfold (85,700 cases increased to 336,600 cases) in the United States. Because of this, it has become a significant area of research, as researchers search for better antimicrobial therapies, diagnostic assays, and prevention tactics.   ASM recently invited Alice Guh, MD, MPH, of the Centers for Disease Control and Prevention, to present the most recent C. difficile research as part of the Hot Topics in Clinical Microbiology series*. In her presentation, ‘Update on Clostridium difficile Infection’, Guh first describes the changing epidemiology of C. difficile infections (CDI), updating the data from the CDC’s Emerging Infections Program (EIP) and their long-term surveillance of CDI within the United States.

Guh further reviews current CDI diagnostic testing and its associated challenges. She highlights the benefits and downfalls of traditional enzyme immunoassay to detect C. difficile toxins compared to the nucleic acid amplification tests (NAAT) first put to widespread use in 2009.

Finally, Guh describes the role of asymptomatic carriers in C. difficile transmission. Her review of the literature presents best practices to trace transmission from asymptomatic carriers as well as suggested strategies to stop this transmission.

To read the article in its entirety please click on the following link:

https://www.asm.org/index.php/clinmicro-blog/item/6264-hot-topics-in-clinical-microbiology-clostridium-difficile