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Article: Oxygen response and tolerance mechanisms in Clostridioides difficile

Kint, Nicolas / Morvan, Claire / Martin-Verstraete, Isabelle

Current opinion in microbiology. 2022 Feb., v. 65

2022

Abstract: While the gut is typically thought of as anoxic, there are two intersecting and decreasing oxygen gradients that are observed in the gut: oxygen decreases from the small to the large intestine and from the intestinal epithelium toward the colon lumen. ... ...

Abstract	While the gut is typically thought of as anoxic, there are two intersecting and decreasing oxygen gradients that are observed in the gut: oxygen decreases from the small to the large intestine and from the intestinal epithelium toward the colon lumen. Gut oxygen levels also increase following antibiotic induced-dysbiosis. While dysbiosis favors growth of Clostridioides difficile, the oxygen increase also causes stress to this anaerobic enteropathogen. To circumvent oxygen threat, C. difficile has developed efficient strategies: sporulation, biofilm formation, the rerouting of central metabolism and the production of oxygen detoxification enzymes. Especially, reverse rubrerythrins and flavodiiron proteins involved in oxygen reduction are crucial in C. difficile ability to tolerate and survive the oxygen concentrations encountered in the gastrointestinal tract. Two regulators, σᴮ and PerR, play pivotal role in the mastering of these adaptive responses by controlling the various systems that protect cells from oxidative damages.
Keywords	Clostridium difficile ; antibiotics ; biofilm ; colon ; digestive tract ; dysbiosis ; enteropathogens ; intestinal mucosa ; metabolism ; microbiology ; oxygen ; sporulation
Language	English
Dates of publication	2022-02
Size	p. 175-182.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1418474-6
ISSN	1879-0364 ; 1369-5274
ISSN (online)	1879-0364
ISSN	1369-5274
DOI	10.1016/j.mib.2021.11.009
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The multiplicity of thioredoxin systems meets the specific lifestyles of Clostridia.

Anjou, Cyril / Lotoux, Aurélie / Zhukova, Anna / Royer, Marie / Caulat, Léo C / Capuzzo, Elena / Morvan, Claire / Martin-Verstraete, Isabelle

PLoS pathogens

2024 Volume 20, Issue 2, Page(s) e1012001

Abstract: Cells are unceasingly confronted by oxidative stresses that oxidize proteins on their cysteines. The thioredoxin (Trx) system, which is a ubiquitous system for thiol and protein repair, is composed of a thioredoxin (TrxA) and a thioredoxin reductase ( ... ...

Abstract	Cells are unceasingly confronted by oxidative stresses that oxidize proteins on their cysteines. The thioredoxin (Trx) system, which is a ubiquitous system for thiol and protein repair, is composed of a thioredoxin (TrxA) and a thioredoxin reductase (TrxB). TrxAs reduce disulfide bonds of oxidized proteins and are then usually recycled by a single pleiotropic NAD(P)H-dependent TrxB (NTR). In this work, we first analyzed the composition of Trx systems across Bacteria. Most bacteria have only one NTR, but organisms in some Phyla have several TrxBs. In Firmicutes, multiple TrxBs are observed only in Clostridia, with another peculiarity being the existence of ferredoxin-dependent TrxBs. We used Clostridioides difficile, a pathogenic sporulating anaerobic Firmicutes, as a model to investigate the biological relevance of TrxB multiplicity. Three TrxAs and three TrxBs are present in the 630Δerm strain. We showed that two systems are involved in the response to infection-related stresses, allowing the survival of vegetative cells exposed to oxygen, inflammation-related molecules and bile salts. A fourth TrxB copy present in some strains also contributes to the stress-response arsenal. One of the conserved stress-response Trx system was found to be present both in vegetative cells and in the spores and is under a dual transcriptional control by vegetative cell and sporulation sigma factors. This Trx system contributes to spore survival to hypochlorite and ensure proper germination in the presence of oxygen. Finally, we found that the third Trx system contributes to sporulation through the recycling of the glycine-reductase, a Stickland pathway enzyme that allows the consumption of glycine and contributes to sporulation. Altogether, we showed that Trx systems are produced under the control of various regulatory signals and respond to different regulatory networks. The multiplicity of Trx systems and the diversity of TrxBs most likely meet specific needs of Clostridia in adaptation to strong stress exposure, sporulation and Stickland pathways.
MeSH term(s)	Bacteria/metabolism ; Thioredoxin-Disulfide Reductase/genetics ; Thioredoxin-Disulfide Reductase/chemistry ; Thioredoxin-Disulfide Reductase/metabolism ; Thioredoxins/metabolism ; Firmicutes/metabolism ; Oxygen ; Glycine
Chemical Substances	Thioredoxin-Disulfide Reductase (EC 1.8.1.9) ; Thioredoxins (52500-60-4) ; Oxygen (S88TT14065) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1012001
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Article ; Online: Oxygen response and tolerance mechanisms in Clostridioides difficile.

Kint, Nicolas / Morvan, Claire / Martin-Verstraete, Isabelle

Current opinion in microbiology

2021 Volume 65, Page(s) 175–182

Abstract	While the gut is typically thought of as anoxic, there are two intersecting and decreasing oxygen gradients that are observed in the gut: oxygen decreases from the small to the large intestine and from the intestinal epithelium toward the colon lumen. Gut oxygen levels also increase following antibiotic induced-dysbiosis. While dysbiosis favors growth of Clostridioides difficile, the oxygen increase also causes stress to this anaerobic enteropathogen. To circumvent oxygen threat, C. difficile has developed efficient strategies: sporulation, biofilm formation, the rerouting of central metabolism and the production of oxygen detoxification enzymes. Especially, reverse rubrerythrins and flavodiiron proteins involved in oxygen reduction are crucial in C. difficile ability to tolerate and survive the oxygen concentrations encountered in the gastrointestinal tract. Two regulators, σ
MeSH term(s)	Clostridioides ; Clostridioides difficile ; Clostridium Infections ; Dysbiosis ; Gastrointestinal Tract ; Humans ; Oxygen
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2021-12-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1418474-6
ISSN	1879-0364 ; 1369-5274
ISSN (online)	1879-0364
ISSN	1369-5274
DOI	10.1016/j.mib.2021.11.009
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Article: Responses of Clostridia to oxygen: from detoxification to adaptive strategies

Morvan, Claire / Folgosa, Filipe / Kint, Nicolas / Teixeira, Miguel / Martin‐Verstraete, Isabelle

Environmental microbiology. 2021 Aug., v. 23, no. 8

2021

Abstract: Clostridia comprise bacteria of environmental, biotechnological and medical interest and many commensals of the gut microbiota. Because of their strictly anaerobic lifestyle, oxygen is a major stress for Clostridia. However, recent data showed that these ...

Abstract	Clostridia comprise bacteria of environmental, biotechnological and medical interest and many commensals of the gut microbiota. Because of their strictly anaerobic lifestyle, oxygen is a major stress for Clostridia. However, recent data showed that these bacteria can cope with O₂ better than expected for obligate anaerobes through their ability to scavenge, detoxify and consume O₂. Upon O₂ exposure, Clostridia redirect their central metabolism onto pathways less O₂‐sensitive and induce the expression of genes encoding enzymes involved in O₂‐reduction and in the repair of oxidized damaged molecules. While Faecalibacterium prausnitzii efficiently consumes O₂ through a specific extracellular electron shuttling system requiring riboflavin, enzymes such as rubrerythrins and flavodiiron proteins with NAD(P)H‐dependent O₂‐ and/or H₂O₂‐reductase activities are usually encoded in other Clostridia. These two classes of enzymes play indeed a pivotal role in O₂ tolerance in Clostridioides difficile and Clostridium acetobutylicum. Two main signalling pathways triggering O₂‐induced responses have been described so far in Clostridia. PerR acts as a key regulator of the O₂‐ and/or reactive oxygen species–defence machinery while in C. difficile, σᴮ, the sigma factor of the general stress response also plays a crucial role in O₂ tolerance by controlling the expression of genes involved in O₂ scavenging and repair systems.
Keywords	Clostridium acetobutylicum ; Clostridium difficile ; anaerobes ; intestinal microorganisms ; lifestyle ; metabolism ; oxidation ; oxygen ; riboflavin ; sigma factors ; stress response
Language	English
Dates of publication	2021-08
Size	p. 4112-4125.
Publishing place	John Wiley & Sons, Inc.
Document type	Article
Note	REVIEW
ZDB-ID	2020213-1
ISSN	1462-2920 ; 1462-2912
ISSN (online)	1462-2920
ISSN	1462-2912
DOI	10.1111/1462-2920.15665
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Article ; Online: Responses of Clostridia to oxygen: from detoxification to adaptive strategies.

Morvan, Claire / Folgosa, Filipe / Kint, Nicolas / Teixeira, Miguel / Martin-Verstraete, Isabelle

Environmental microbiology

2021 Volume 23, Issue 8, Page(s) 4112–4125

Abstract	Clostridia comprise bacteria of environmental, biotechnological and medical interest and many commensals of the gut microbiota. Because of their strictly anaerobic lifestyle, oxygen is a major stress for Clostridia. However, recent data showed that these bacteria can cope with O
MeSH term(s)	Clostridioides difficile ; Clostridium/genetics ; Clostridium acetobutylicum ; Oxygen ; Sigma Factor
Chemical Substances	Sigma Factor ; Oxygen (S88TT14065)
Language	English
Publishing date	2021-07-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2020213-1
ISSN	1462-2920 ; 1462-2912
ISSN (online)	1462-2920
ISSN	1462-2912
DOI	10.1111/1462-2920.15665
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Article ; Online: Observational, Retrospective Evaluation of a New Nurse-Initiated Emergency Department Pain Management Protocol.

Muscat, Coline / Fey, Stéphanie / Lacan, Magalie / Morvan, Claire / Belle, Loïc / Lesage, Patrick

Pain management nursing : official journal of the American Society of Pain Management Nurses

2021 Volume 22, Issue 4, Page(s) 485–489

Abstract: Background: Triage nurses are important in pain management and in early relief of pain among patients admitted to the emergency department (ED).: Aims: To assess a new nurse-initiated pain management protocol, without the requirement for medical ... ...

Abstract	Background: Triage nurses are important in pain management and in early relief of pain among patients admitted to the emergency department (ED). Aims: To assess a new nurse-initiated pain management protocol, without the requirement for medical prescription, wich was implemented in October 2016 for patients with moderate or severe pain in the ED. It allows the administration of oral acetaminophen and oral oxycodone chlorydrate during the first evaluation of the patient by a nurse and eliminates the use of codeine or tramadol. Methods: We conducted a comparative, single-center, retrospective study that looked at the outcomes of a new nursing protocol for patients aged ≥16 years with moderate to severe pain. The primary outcome was the percentage of increase of analgesics delivered by the nurse. Results: A total of 756 patients were included: 377 before and 379 after protocol implementation. Oral analgesic use on admission increased from 44.3% to 57.8% (p < .001), and from 50.2% to 76.6% among patients with severe pain (p < .001). Strong opioid analgesic administration increased from 2.1% to 41.2%. This increase was also observed among those with moderate pain (1.4% to 13.3%; p < .001) and those with severe pain (2.6% to 62.6%; p < .001). Analgesic prescriptions added by the clinician decreased from 28.6% to 21.4% (p = .028). Conclusions: We observed an increase in analgesic administration after the implementation of a new nurse-initiated pain treatment protocol, especially an increase in oral opioid analgesics, for patients with moderate to severe pain.
MeSH term(s)	Analgesics/therapeutic use ; Analgesics, Opioid/therapeutic use ; Emergency Service, Hospital ; Humans ; Pain/drug therapy ; Pain Management ; Retrospective Studies
Chemical Substances	Analgesics ; Analgesics, Opioid
Language	English
Publishing date	2021-02-02
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2213260-0
ISSN	1532-8635 ; 1524-9042
ISSN (online)	1532-8635
ISSN	1524-9042
DOI	10.1016/j.pmn.2020.12.013
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Zs.MO 514: Show issues

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Article ; Online: 6S RNA-Dependent Susceptibility to RNA Polymerase Inhibitors.

Esberard, Marick / Hallier, Marc / Liu, Wenfeng / Morvan, Claire / Bossi, Lionello / Figueroa-Bossi, Nara / Felden, Brice / Bouloc, Philippe

Antimicrobial agents and chemotherapy

2022 Volume 66, Issue 5, Page(s) e0243521

Abstract: Bacterial small RNAs (sRNAs) contribute to a variety of regulatory mechanisms that modulate a wide range of pathways, including metabolism, virulence, and antibiotic resistance. We investigated the involvement of sRNAs in rifampicin resistance in the ... ...

Abstract	Bacterial small RNAs (sRNAs) contribute to a variety of regulatory mechanisms that modulate a wide range of pathways, including metabolism, virulence, and antibiotic resistance. We investigated the involvement of sRNAs in rifampicin resistance in the opportunistic pathogen Staphylococcus aureus. Using a competition assay with an sRNA mutant library, we identified 6S RNA as being required for protection against low concentrations of rifampicin, an RNA polymerase (RNAP) inhibitor. This effect applied to rifabutin and fidaxomicin, two other RNAP-targeting antibiotics. 6S RNA is highly conserved in bacteria, and its absence in two other major pathogens, Salmonella enterica and Clostridioides difficile, also impaired susceptibility to RNAP inhibitors. In S. aureus, 6S RNA is produced from an autonomous gene and accumulates in stationary phase. In contrast to what was reported for Escherichia coli, S. aureus 6S RNA does not appear to play a critical role in the transition from exponential to stationary phase but affects σ
MeSH term(s)	DNA-Directed RNA Polymerases/genetics ; DNA-Directed RNA Polymerases/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Gene Expression Regulation, Bacterial ; RNA, Bacterial/genetics ; RNA, Untranslated ; Rifampin/pharmacology ; Sigma Factor/genetics ; Sigma Factor/metabolism ; Staphylococcus aureus/genetics ; Staphylococcus aureus/metabolism ; Transcription, Genetic
Chemical Substances	6S RNA ; RNA, Bacterial ; RNA, Untranslated ; Sigma Factor ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2022-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/aac.02435-21
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Article ; Online: Do Primocolonizing Bacteria Enable Bacteroides thetaiotaomicron Intestinal Colonization Independently of the Capacity To Consume Oxygen?

Halpern, David / Morvan, Claire / Derré-Bobillot, Aurélie / Meylheuc, Thierry / Guillemet, Mélanie / Rabot, Sylvie / Gruss, Alexandra

mSphere

2021 Volume 6, Issue 3

Abstract: Aerobic bacteria are frequent primocolonizers of the human naive intestine. Their generally accepted role is to eliminate oxygen, which would allow colonization by anaerobes that subsequently dominate bacterial gut populations. In this hypothesis-based ... ...

Abstract	Aerobic bacteria are frequent primocolonizers of the human naive intestine. Their generally accepted role is to eliminate oxygen, which would allow colonization by anaerobes that subsequently dominate bacterial gut populations. In this hypothesis-based study, we revisited this dogma experimentally in a germfree mouse model as a mimic of the germfree newborn. We varied conditions leading to the establishment of the dominant intestinal anaerobe
MeSH term(s)	Aerobiosis ; Animals ; Bacteria/classification ; Bacteria/metabolism ; Bacteroides thetaiotaomicron/physiology ; Humans ; Intestines/microbiology ; Mice ; Mice, Inbred BALB C ; Microbial Viability ; Oxygen/metabolism ; Specific Pathogen-Free Organisms
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2021-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/mSphere.00232-19
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Article ; Online: Finding sRNA-associated phenotypes by competition assays: An example with Staphylococcus aureus.

Le Lam, Thao Nguyen / Morvan, Claire / Liu, Wenfeng / Bohn, Chantal / Jaszczyszyn, Yan / Bouloc, Philippe

Methods (San Diego, Calif.)

2017 Volume 117, Page(s) 21–27

Abstract: Bacteria optimize their fitness in response to a changing environment by tight regulation of gene expression. Regulation can be controlled at both transcriptional and post-transcriptional levels via key players such as sigma factors, regulatory proteins ... ...

Abstract	Bacteria optimize their fitness in response to a changing environment by tight regulation of gene expression. Regulation can be controlled at both transcriptional and post-transcriptional levels via key players such as sigma factors, regulatory proteins and regulatory RNAs. The identification of phenotypes associated with gene deletions is the established method for finding gene functions but may require testing many conditions for each studied mutant. As regulatory RNAs often contribute to fine-tuning gene expression, phenotypes associated with their inactivation are often weak and difficult to detect. Nevertheless, minor phenotypes conferring modest advantages, may allow bacteria to emerge after some generations under selective pressure. A strategy employing DNA barcodes can be used to perform competition experiments between mutants and to monitor fitness associated with mutations in different growth conditions. We combined this strategy with deep sequencing to study regulatory RNAs in Staphylococcus aureus, a major opportunistic pathogen.
Language	English
Publishing date	2017-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1066584-5
ISSN	1095-9130 ; 1046-2023
ISSN (online)	1095-9130
ISSN	1046-2023
DOI	10.1016/j.ymeth.2016.11.018
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Article: Assessment of

Liu, Wenfeng / Rochat, Tatiana / Toffano-Nioche, Claire / Le Lam, Thao Nguyen / Bouloc, Philippe / Morvan, Claire

Frontiers in microbiology

2018 Volume 9, Page(s) 228

Abstract: Bacterial regulatory RNAs have been extensively studied for over a decade, and are progressively being integrated into the complex genetic regulatory network. Transcriptomic arrays, recent deep-sequencing data and bioinformatics suggest that bacterial ... ...

Abstract	Bacterial regulatory RNAs have been extensively studied for over a decade, and are progressively being integrated into the complex genetic regulatory network. Transcriptomic arrays, recent deep-sequencing data and bioinformatics suggest that bacterial genomes produce hundreds of regulatory RNAs. However, while some have been authenticated, the existence of the others varies according to strains and growth conditions, and their detection fluctuates with the methodologies used for data acquisition and interpretation. For example, several small RNA (sRNA) candidates are now known to be parts of UTR transcripts. Accurate annotation of regulatory RNAs is a complex task essential for molecular and functional studies. We defined
Language	English
Publishing date	2018-02-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2018.00228
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