Lactic acid production by Streptococcus thermophilus alters Clostridium difficile infection and in vitro Toxin A production.
Antibiotic treatment to treat specific infections has the potential to effectively target the offending microbe as well as other microbes that colonize sites within a host. Antibiotic-associated diarrhea (AAD) is a classic example resulting from disruption of host microbial communities; 20% of patients with AAD are likely to become colonized with Clostridium difficile. Restoration of a "normal" microbial community within the host using probiotic bacteria is one approach to circumvent AAD and C. difficile infection. The goals of this study were to assess the interactions between Streptococcus thermophilus, a potential probiotic organism and C. difficile using both in vitro and in vivo systems. Exposure of C. difficile to filtered supernatants from S. thermophilus showed a dose-dependent, bactericidal effect due to lactic acid. Additional studies show that levels of lactic acid (10 mM) that did not inhibit bacterial growth had the potential to decrease tcdA expression and TcdA release into the extracellular milieu. In vivo, treatment with viable S. thermophilus significantly increased luminal levels of lactate in the cecum compared with UV-irradiated S. thermophilus. In the context of infection with C. difficile, mice treated with viable S. thermophilus exhibited 46% less weight loss compared with untreated controls; moreover, less pathology, diarrhea, and lower detectable toxin levels in cecal contents were evident more often in S. thermophillus treated mice. A significant, inverse correlation (Spearman r = -0.942, p = 0.017) between the levels of luminal lactate and abundance of C. difficile were noted suggesting that lactate produced by S. thermophilus is a factor impacting the progression of C. difficile infection in the murine system.
Department of Internal Medicine/Division of Infectious Diseases, University of Virginia, Charlottesville, VA, USA. glk3a@virginia.edu
Glynis L
GL
Kolling
Martin
M
Wu
Cirle A
CA
Warren
Evelyn
E
Durmaz
Todd R
TR
Klaenhammer
Michael P
MP
Timko
Richard L
RL
Guerrant
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D000898:Antibiosis; D001427:Bacterial Toxins; D001835:Body Weight; D002432:Cecum / Q000737:chemistry; D016360:Clostridioides difficile / Q000187:drug effects* / Q000472:pathogenicity*; D003015:Clostridium Infections / Q000473:pathology; D003967:Diarrhea / Q000473:pathology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D051379:Mice; D050296:Microbial Viability / Q000187:drug effects; D048249:Streptococcus thermophilus / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; D019344:Lactic Acid