Metabolic adaption to extracellular pyruvate triggers biofilm formation in<i>Clostridioides difficile</i>

Tremblay, Yannick D. N.; Durand, Benjamin; Hamiot, Audrey; Martin‐Verstraete, Isabelle; Oberkampf, Marine; Monot, Marc; Dupuy, Bruno

doi:10.1101/2021.01.23.427917

Cited by 5 publications

(28 citation statements)

References 67 publications

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“…Moreover, we did not only confirm the importance of c-di-GMP signaling in biofilm formation but further suggested a central role for SigL/RpoN in C. difficile biofilms and conclude that research on this well-conserved regulator is hitherto underrepresented ( Table 2 ). Of note, Tremblay et al (2021) recently suggested a role for SigL/RpoN in C. difficile biofilms. Likewise, the data presented here emphasize the importance to characterize various still uncharacterized transcriptional regulators and two-component systems of which several were induced in aggregate biofilms ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

What’s a Biofilm?—How the Choice of the Biofilm Model Impacts the Protein Inventory of Clostridioides difficile

et al. 2021

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The anaerobic pathogen Clostridioides difficile is perfectly equipped to survive and persist inside the mammalian intestine. When facing unfavorable conditions C. difficile is able to form highly resistant endospores. Likewise, biofilms are currently discussed as form of persistence. Here a comprehensive proteomics approach was applied to investigate the molecular processes of C. difficile strain 630Δerm underlying biofilm formation. The comparison of the proteome from two different forms of biofilm-like growth, namely aggregate biofilms and colonies on agar plates, revealed major differences in the formation of cell surface proteins, as well as enzymes of its energy and stress metabolism. For instance, while the obtained data suggest that aggregate biofilm cells express both flagella, type IV pili and enzymes required for biosynthesis of cell-surface polysaccharides, the S-layer protein SlpA and most cell wall proteins (CWPs) encoded adjacent to SlpA were detected in significantly lower amounts in aggregate biofilm cells than in colony biofilms. Moreover, the obtained data suggested that aggregate biofilm cells are rather actively growing cells while colony biofilm cells most likely severely suffer from a lack of reductive equivalents what requires induction of the Wood-Ljungdahl pathway and C. difficile’s V-type ATPase to maintain cell homeostasis. In agreement with this, aggregate biofilm cells, in contrast to colony biofilm cells, neither induced toxin nor spore production. Finally, the data revealed that the sigma factor SigL/RpoN and its dependent regulators are noticeably induced in aggregate biofilms suggesting an important role of SigL/RpoN in aggregate biofilm formation.

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Section: Discussionmentioning

confidence: 99%

What’s a Biofilm?—How the Choice of the Biofilm Model Impacts the Protein Inventory of Clostridioides difficile

et al. 2021

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“…However, the diversity of conditions also makes it difficult to compare studies and draw accurate conclusions. The recent development of a semi-defined medium that supports biofilm formation may help bridge those gaps in knowledge and resolve current discrepancies [ 192 ].…”

Section: Biofilm Formation In C Difficilementioning

confidence: 99%

“…The biofilm matrix is typically composed of DNA, polysaccharides, and proteins, but the composition varies according to species. For C. difficile , eDNA is an essential structural biofilm component under all conditions tested [ 184 , 192 , 201 , 204 ]. Specifically, adding DNAse I before biofilms were formed prevented their formation [ 184 , 201 ], and DNAse I dispersed pre-formed biofilms [ 184 , 204 ].…”

Section: Biofilm Formation In C Difficilementioning

confidence: 99%

“…However, calcofluor is not specific for cellulose as it also recognizes β-1,3 or β-1,4 exopolysaccharides, which includes PS-II. Moreover, deletion of the bscA orthologue ( ccsA ) encoding a glycosyltransferase involved in cellulose synthesis did not significantly alter DOC-induced biofilm formation [ 192 ]. Despite evidence that EPS may contribute to the biofilm matrix, treatment with NaIO 4 hydrolyzing polysaccharides did not disrupt pre-formed biofilms in vitro [ 184 ].…”

Section: Biofilm Formation In C Difficilementioning

confidence: 99%

“…Like EPS, proteins are probably not essential for the stability of the biofilm because a treatment with proteinase K did not disperse pre-formed biofilms [ 184 ]. However, biofilms formed in a semi-defined medium were sensitive to the proteinase K treatment [ 192 ]. Furthermore, adding proteinase K before biofilms are formed prevents biofilm formation [ 184 , 201 ].…”

Section: Biofilm Formation In C Difficilementioning

confidence: 99%

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Wolf in Sheep’s Clothing: Clostridioides difficile Biofilm as a Reservoir for Recurrent Infections

et al. 2021

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The microbiota inhabiting the intestinal tract provide several critical functions to its host. Microorganisms found at the mucosal layer form organized three-dimensional structures which are considered to be biofilms. Their development and functions are influenced by host factors, host-microbe interactions, and microbe-microbe interactions. These structures can dictate the health of their host by strengthening the natural defenses of the gut epithelium or cause disease by exacerbating underlying conditions. Biofilm communities can also block the establishment of pathogens and prevent infectious diseases. Although these biofilms are important for colonization resistance, new data provide evidence that gut biofilms can act as a reservoir for pathogens such as Clostridioides difficile. In this review, we will look at the biofilms of the intestinal tract, their contribution to health and disease, and the factors influencing their formation. We will then focus on the factors contributing to biofilm formation in C. difficile, how these biofilms are formed, and their properties. In the last section, we will look at how the gut microbiota and the gut biofilm influence C. difficile biofilm formation, persistence, and transmission.

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Novel drivers of virulence inClostridioides difficileidentified via context-specific metabolic network analysis

Jenior

Leslie

Powers

et al. 2020

Preprint

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Clostridioides difficile is a Gram-positive, sporulating anaerobe that has become the leading cause of hospital-acquired infections. Over the previous decade, many studies have demonstrated the importance of metabolism in numerous aspects of C. difficile biology from initial colonization to regulation of virulence factors. Additionally, due to growing threats of antibiotic resistance and recurrent infection, targeting components of metabolism presents a novel possible approach to combat this infection. In the past, genome-scale metabolic network analysis of bacteria has enabled systematic investigation of the genetic and metabolic properties that potentially contribute to downstream phenotypes as well as prediction of outcome from perturbations to these pathways. These predictions ultimately create a platform for high-throughput identification and screening of metabolic targets prior to laboratory testing. To accomplish these goals in C. difficile, we constructed highly-curated genome-scale metabolic network reconstructions (GENREs) for a well-studied laboratory strain of the pathogen (str. 630) as well as a more recently characterized hyper-virulent isolate (str. R20291). These computational modeling platforms account for key components of C. difficile core metabolism and nutrient acquisition systems to recapitulate metabolic behaviors within the complex milieu of the gut. Simulating the impact of single-gene deletions resulted in accuracies of ~89.9% for both GENREs compared with transposon mutant libraries. Further analysis of both strains also revealed significant correlations between in silico and experimentally measured growth in carbon source utilization screens (p-values ≤ 0.002), with positive predictive values of ~95.0%. Subsequently, we generated context-specific models by integrating transcriptomic data from C. difficile grown in vitro or during in vivo infection. Simulations also predicted the consistent inverse patterns of carbohydrate and amino acid catabolism that corresponded with differential virulence factor expression measured experimentally. Collectively, our results indicate that GENRE-based analyses of C. difficile are an effective means for gaining novel insight into metabolism as it relates to pathogenesis and provides a platform for the identification of novel therapeutic targets.

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Metabolic adaption to extracellular pyruvate triggers biofilm formation inClostridioides difficile

Cited by 5 publications

References 67 publications

What’s a Biofilm?—How the Choice of the Biofilm Model Impacts the Protein Inventory of Clostridioides difficile

What’s a Biofilm?—How the Choice of the Biofilm Model Impacts the Protein Inventory of Clostridioides difficile

Wolf in Sheep’s Clothing: Clostridioides difficile Biofilm as a Reservoir for Recurrent Infections

Novel drivers of virulence inClostridioides difficileidentified via context-specific metabolic network analysis

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