<i>Clostridium difficile</i>infection

Viswanathan, V. K.; Mallozzi, Michael; Vedantam, Gayatri

doi:10.4161/gmic.1.4.12706

Cited by 94 publications

(57 citation statements)

References 137 publications

(146 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(Hunt and Ballard, 2013; Lucado et al, 2012). C. difficile establishes infection following disruption of the indigenous microbiota, usually the result of preceding antibiotic treatment (Rupnik et al, 2009; Viswanathan et al, 2010). Antibiotic treatments for C. difficile infection (CDI) are often ineffective, (Huang et al, 2009; Johnson, 2009; Pepin et al, 2005) and complications associated with recurrent CDI in hospitalized patients interfere with medical therapies until infection is brought under control (Chopra et al, 2010; Dubberke et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Innate Immune Defenses Mediated by Two ILC Subsets Are Critical for Protection against Acute Clostridium difficile Infection

Abt

Lewis

Caballero

et al. 2015

Cell Host & Microbe

235

246

View full text Add to dashboard Cite

Summary Infection with the opportunistic enteric pathogen Clostridium difficile is an increasingly common clinical complication that follows antibiotic treatment-induced gut microbiota perturbation. Innate lymphoid cells (ILCs) are early responders to enteric pathogens; however, their role during C. difficile infection is undefined. To identify immune pathways that mediate recovery from C. difficile infection, we challenged C57BL/6, Rag1−/−, which lack T and B cells, and Rag2−/− Il2rg−/− (Ragγc−/−) mice, which additionally lack ILCs, with C. difficile. In contrast to Rag1−/− mice, ILC-deficient Ragγc−/− mice rapidly succumbed to infection. Rag1−/−, but not Ragγc−/− mice, upregulate expression of ILC1 or ILC3 associated proteins following C. difficile infection. Protection against infection was restored by transferring ILCs into Ragγc−/− mice. While ILC3s made a minor contribution to resistance, loss of IFN-γ or T-bet-expressing ILC1s in Rag1−/− mice increased susceptibility to C. difficile. These data demonstrate a critical role for ILC1s in defense against C. difficile.

show abstract

Section: Introductionmentioning

confidence: 99%

Innate Immune Defenses Mediated by Two ILC Subsets Are Critical for Protection against Acute Clostridium difficile Infection

Abt

Lewis

Caballero

et al. 2015

Cell Host & Microbe

235

246

View full text Add to dashboard Cite

show abstract

“…Clostridium difficile, a Gram-positive spore-forming bacterium, is the major cause of intestinal diseases associated with antibiotic therapy (Viswanathan et al, 2010). Clinical manifestations in humans range from asymptomatic colonization or mild diarrhoea to pseudomembranous colitis and death (Kelly & LaMont, 1998).…”

Section: Introductionmentioning

confidence: 99%

Genomic and expression analysis of the vanG-like gene cluster of Clostridium difficile

et al. 2013

View full text Add to dashboard Cite

Primary antibiotic treatment of Clostridium difficile intestinal diseases requires metronidazole or vancomycin therapy. A cluster of genes homologous to enterococcal glycopeptides resistance vanG genes was found in the genome of C. difficile 630, although this strain remains sensitive to vancomycin. This vanG-like gene cluster was found to consist of five ORFs: the regulatory region consisting of vanR and vanS and the effector region consisting of vanG, vanXY and vanT. We found that 57 out of 83 C. difficile strains, representative of the main lineages of the species, harbour this vanG-like cluster. The cluster is expressed as an operon and, when present, is found at the same genomic location in all strains. The vanG, vanXY and vanT homologues in C. difficile 630 are co-transcribed and expressed to a low level throughout the growth phases in the absence of vancomycin. Conversely, the expression of these genes is strongly induced in the presence of subinhibitory concentrations of vancomycin, indicating that the vanG-like operon is functional at the transcriptional level in C. difficile. Hydrophilic interaction liquid chromatography (HILIC-HPLC) and MS analysis of cytoplasmic peptidoglycan precursors of C. difficile 630 grown without vancomycin revealed the exclusive presence of a UDP-MurNAc-pentapeptide with an alanine at the C terminus. UDP-MurNAc-pentapeptide [D-Ala] was also the only peptidoglycan precursor detected in C. difficile grown in the presence of vancomycin, corroborating the lack of vancomycin resistance. Peptidoglycan structures of a vanG-like mutant strain and of a strain lacking the vanG-like cluster did not differ from the C. difficile 630 strain, indicating that the vanGlike cluster also has no impact on cell-wall composition.

show abstract

“…Clostridium difficile, a Gram-positive spore-forming bacterium, is the major cause of intestinal diseases associated with antibiotic therapy such as ampicillin, clindamycin, and cephalosporins, which disrupt the barrier intestinal flora and allow C. difficile colonization (1,2). Clinical manifestations range from asymptomatic colonization or mild diarrhea to pseudomembranous colitis (3).…”

mentioning

confidence: 99%

Clostridium difficile Has an Original Peptidoglycan Structure with a High Level of N-Acetylglucosamine Deacetylation and Mainly 3-3 Cross-links

Peltier

Courtin

Meouche

et al. 2011

Journal of Biological Chemistry

115

157

View full text Add to dashboard Cite

The structure of the vegetative cell wall peptidoglycan of Clostridium difficile was determined by analysis of its constituent muropeptides with a combination of reverse-phase high pressure liquid chromatography separation of muropeptides, amino acid analysis, mass spectrometry and tandem mass spectrometry. The structures assigned to 36 muropeptides evidenced several original features in C. difficile vegetative cell peptidoglycan. First, it is characterized by a strikingly high level of N-acetylglucosamine deacetylation. In addition, the majority of dimers (around 75%) contains A 2 pm 3 3 A 2 pm 3 (A 2 pm, 2,6-diaminopimelic acid) cross-links and only a minority of the more classical Ala 4 3 A 2 pm 3 cross-links. Moreover, a significant amount of muropeptides contains a modified tetrapeptide stem ending in Gly instead of D-Ala 4 . Two L,D-transpeptidases homologues encoding genes present in the genome of C. difficile 630 and named ldt cd1 and ldt cd2 , were inactivated. The inactivation of either ldt cd1 or ldt cd2 significantly decreased the abundance of 3-3 cross-links, leading to a marked decrease of peptidoglycan reticulation and demonstrating that both ldt cd1 -and ldt cd2 -encoded proteins have a redundant L,D-transpeptidase activity. The contribution of 3-3 cross-links to peptidoglycan synthesis increased in the presence of ampicillin, indicating that this drug does not inhibit the L,D-transpeptidation pathway in C. difficile.Clostridium difficile, a Gram-positive spore-forming bacterium, is the major cause of intestinal diseases associated with antibiotic therapy such as ampicillin, clindamycin, and cephalosporins, which disrupt the barrier intestinal flora and allow C. difficile colonization (1, 2). Clinical manifestations range from asymptomatic colonization or mild diarrhea to pseudomembranous colitis (3). The main virulence factors have been identified as toxin A and B (4). Recent outbreaks have led to increasing morbidity and mortality and have been associated with a new highly virulent strain (BI/NAP1/027) of C. difficile.Antibiotic treatment of C. difficile-associated disease requires metronidazole or vancomycin therapy.Peptidoglycan ( (9), which were originally detected in Enterococcus faecium (Ldt fm ) (10) and then in other Gram-positive bacteria (11,12), in mycobacteria (13-15), and in Escherichia coli (16,17). Ldts use acyl donors containing a tetrapeptide stem (9) and were consequently expected to confer resistance to ␤-lactams (10, 18).Another possible variation of the PG structure is the occurrence of N-deacetylation or O-acetylation of glycan strands, either on GlcNAc or on MurNAc residues (19,20). N-Deacetylation in Listeria monocytogenes (21) or Streptococcus pneumoniae (22) and O-acetylation in Staphylococcus aureus have been linked to lysozyme resistance (23).The PGs of C. difficile should have some specificities regarding the effect of antibiotics inhibiting PG biosynthesis; C. difficile, although susceptible to ␤-lactams, exhibits higher minimal inhibitory concentrations than in oth...

show abstract

Clostridium difficileinfection

Cited by 94 publications

References 137 publications

Innate Immune Defenses Mediated by Two ILC Subsets Are Critical for Protection against Acute Clostridium difficile Infection

Innate Immune Defenses Mediated by Two ILC Subsets Are Critical for Protection against Acute Clostridium difficile Infection

Genomic and expression analysis of the vanG-like gene cluster of Clostridium difficile

Clostridium difficile Has an Original Peptidoglycan Structure with a High Level of N-Acetylglucosamine Deacetylation and Mainly 3-3 Cross-links

Contact Info

Product

Resources

About