Drivers of Clostridioides difficile hypervirulent ribotype 027 spore germination, vegetative cell growth and toxin production in vitro

Yuille, S.; Mackay, William G.; Morrison, Douglas J.; Tedford, M. C.

doi:10.1016/j.cmi.2019.11.004

Cited by 10 publications

(7 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We showed that communities that reduce the external pH below 6.2 inhibit C. difficile in a pH‐dependent manner, consistent with studies showing that C. difficile has lower viability and rates of sporulation in acidic environments (Wetzel & McBride, 2020; Yuille et␣al , 2020). We note that our in␣vitro system differs from the human gut, lacking the pH‐buffering secretion of bicarbonate by host intestinal epithelial cells.…”

Section: Discussionsupporting

confidence: 88%

“…For example, communities with the same richness invaded with equal abundances of C. difficile showed a wide range of C. difficile abundances at 48 h (Fig 2A). Since environmental pH has been shown to influence C. difficile ’s growth in previous studies (Wetzel & McBride, 2020; Yuille et␣al , 2020), we turned next to investigate how biotic modification of the environment alters the growth of C. difficile . To this end, we grew the set of 15 3–4 member communities for 6 h before invading with low or high initial densities of C. difficile to give the communities time to modify the environment.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Negative interactions determine Clostridioides difficile growth in synthetic human gut communities

Hromada

Qian

Jacobson

et al. 2021

Molecular Systems Biology

View full text Add to dashboard Cite

Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut microbiome. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. Our results show that C. difficile is in a unique class of species that display a strong negative dependence between growth and species richness. We identify molecular mechanisms of inhibition including acidification of the environment and competition over resources. We demonstrate that Clostridium hiranonis strongly inhibits C. difficile partially via resource competition. Increasing the initial density of C. difficile can increase its abundance in the assembled community, but community context determines the maximum achievable C. difficile abundance. Our work suggests that the C. difficile inhibitory potential of defined bacterial therapeutics can be optimized by designing communities featuring a combination of mechanisms including species richness, environment acidification, and resource competition.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Negative interactions determine Clostridioides difficile growth in synthetic human gut communities

Hromada

Qian

Jacobson

et al. 2021

Molecular Systems Biology

View full text Add to dashboard Cite

show abstract

“…Our results demonstrated that communities can inhibit growth of C. difficile by acidifying the environment. We showed that communities that reduce the external pH below 6.2 inhibit C. difficile in a pH-dependent manner, consistent with studies showing that C. difficile has lower viability and rates of sporulation in acidic environments 33,34 . While our in vitro system lacks the pH-buffering secretion of bicarbonate by host intestinal epithelial cells, the amount of bicarbonate buffer in our media (4.8 mM) is within the estimated range in the gastrointestinal tract (2-20mM) 45 , suggesting the observed pH changes in our media could be physiologically relevant.…”

Section: Difficilesupporting

confidence: 89%

“…2a). Since environmental pH has been shown to influence C. difficile's growth in previous studies 33,34 , we turned next to investigate how biotic modification of the environment alters the growth of C. difficile. To this end, we grew the set of 15, 3-4 member communities for six hours and then invaded with low or high initial densities of C. difficile.…”

Section: Environmental Ph Is a Major Factor Influencing C Difficile Growth In Synthetic Communitiesmentioning

confidence: 99%

Species richness determinesC. difficileinvasion outcome in synthetic human gut communities

Hromada

Qian

et al. 2021

Preprint

View full text Add to dashboard Cite

Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of next generation defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile invasion using a diverse synthetic human gut microbiome. Our results show that species richness is a key determinant of C. difficile growth across a wide range of ecological contexts. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. We identify molecular mechanisms of inhibition including acidification of the environment and competition over glucose. We demonstrate that C. difficile's close relative Clostridium hiranonis strongly inhibits C. difficile via a pH-independent mechanism. While increasing the initial density of C. difficile can increase its abundance in the assembled community, the community context determines the maximum achievable C. difficile abundance. Our work suggests that the C. difficile inhibitory potential of defined bacterial therapeutics can be optimized by designing communities that feature a combination of mechanisms including species richness, environment acidification, and resource competition.

show abstract

“…They affect host physiology, including an energy source for colon cells, regulating the intestinal barrier, and affecting inflammatory responses ( Correa-Oliveira et al, 2016 ). SCFAs also inhibit C. difficile toxin production ( Yuille et al, 2020 ), reducing CDI ( McDonald et al, 2018a ; Fachi et al, 2020 ) and inhibiting spore growth ( Battaglioli et al, 2018 ; Hryckowian et al, 2018 ; Neumann-Schaal et al, 2019 ). Like previous studies ( McDonald et al, 2018a ), the CDI group showed decreased butyric acid, propionic acid, acetic acid, and A. muciniphila restored SCFA metabolism, possibly by restoring the intestinal flora balance.…”

Section: Discussionmentioning

confidence: 99%

Akkermansia muciniphila Ameliorates Clostridioides difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

Clostridioides difficile is a common cause of nosocomial infection. Antibiotic-induced dysbiosis in the intestinal microbiota is a core cause of C. difficile infection (CDI). Akkermansia muciniphila plays an active role in maintaining gastrointestinal balance and might offer the protective effects on CDI as probiotics. Here, we investigated the effects and mechanisms of A. muciniphila on CDI. C57BL/6 mice (n = 29) were administered A. muciniphila MucT (3 × 109 CFUs, 0.2 mL) or phosphate-buffered saline (PBS) by oral gavage for 2 weeks. Mice were pretreated with an antibiotic cocktail and subsequently challenged with the C. difficile strain VPI 10463. A. muciniphila treatment prevented weight loss in mice and reduced the histological injury of the colon. And it also alleviated inflammation and improved the barrier function of the intestine. The administration effects of A. muciniphila may be associated with an increase in short-chain fatty acid production and the maintenance of bile acids’ steady-state. Our results provide evidence that administration of A. muciniphila to CDI mice, with an imbalance in the microbial community structure, lead to a decrease in abundance of members of the Enterobacteriaceae and Enterococcaceae. In short, A. muciniphila shows a potential anti-CDI role by modulating gut microbiota and the metabolome.

show abstract

Drivers of Clostridioides difficile hypervirulent ribotype 027 spore germination, vegetative cell growth and toxin production in vitro

Abstract: The material cannot be used for any other purpose without further permission of the publisher and is for private use only. There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.

Cited by 10 publications

References 34 publications

Negative interactions determine Clostridioides difficile growth in synthetic human gut communities

Negative interactions determine Clostridioides difficile growth in synthetic human gut communities

Species richness determinesC. difficileinvasion outcome in synthetic human gut communities

Akkermansia muciniphila Ameliorates Clostridioides difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites

Contact Info

Product

Resources

About