Key publications
Moore P, Kyne L, Martin A, Solomon K (2013). Germination efficiency of clinical Clostridium difficile spores and correlation with ribotype, disease severity and therapy failure.
J Med Microbiol,
62(Pt 9), 1405-1413.
Abstract:
Germination efficiency of clinical Clostridium difficile spores and correlation with ribotype, disease severity and therapy failure.
Spore germination is an important part of the pathogenesis of Clostridium difficile infection (CDI). Spores are resistant to antibiotics, including those therapeutically administered for CDI and strains with a high germination rate are significantly more likely to be implicated in recurrent CDI. The role of germination efficiency in cases of refractory CDI where first-line therapy fails remains unclear. We investigated spore germination efficiencies of clinical C. difficile isolates by measuring drop in OD600 and colony forming efficiency. Ribotype 027 isolates exhibited significantly higher germination efficiencies in the presence of 0.1 % (w/v) sodium taurocholate (51.66 ± 8.75 %; 95 % confidence interval (CI) 47.37-55.95 %) than ribotype 106 (41.91 ± 8.35 %; 95 % CI 37.82-46 %) (P
Abstract.
Author URL.
Solomon K, Martin AJ, O'Donoghue C, Chen X, Fenelon L, Fanning S, Kelly CP, Kyne L (2013). Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses.
J Med Microbiol,
62(Pt 9), 1453-1460.
Abstract:
Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses.
Host anti-toxin immune responses play important roles in Clostridium difficile disease and outcome. The relationship between host immune and inflammatory responses during severe C. difficile infection (CDI) and the risk of mortality has yet to be defined. We aimed to investigate the host systemic IgG anti-toxin immune responses, the in vitro cytotoxicity of the infecting C. difficile ribotyped strain, and the host inflammatory markers and their relationship to CDI disease severity and risk of mortality. Inflammatory markers, co-morbidities and CDI outcomes were recorded in a prospective cohort of 150 CDI cases. Serum anti-cytotoxin a (TcdA) and anti-TcdB IgG titres were measured by ELISA and the infecting C. difficile isolate was ribotyped and the in vitro cytotoxin titre assessed. A low median anti-TcdA IgG titre was significantly associated with 30-day all-cause mortality (P
Abstract.
Author URL.
Solomon K (2013). The host immune response to Clostridium difficile infection.
Ther Adv Infect Dis,
1(1), 19-35.
Abstract:
The host immune response to Clostridium difficile infection.
Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins a and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future.
Abstract.
Author URL.
Solomon K, Kyne L (2012). Clostridium difficile-Associated Colitis: Role of the Immune Response and Approach to Treatment. In (Ed)
Colitis.
Author URL.
Martin A, Solomon K, O'Donoghue C, Hannan M, Fenelon L, Kyne L (2012). Cognitive Impairment Increases Risk of Infection, Recurrence and Death Due to Hospital-onset C. Difficile.
IRISH JOURNAL OF MEDICAL SCIENCE,
181, S229-S229.
Author URL.
Solomon K (2012). Host immune response to C. difficile. European Conference of Clinical Microbiology and Infectious Diseases (ECCMID). 31st Mar - 3rd Apr 2012.
Publications by year
2017
Cairns MD, Preston MD, Hall CL, Gerding DN, Hawkey PM, Kato H, Kim H, Kuijper EJ, Lawley TD, Pituch H, et al (2017). Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages.
J Clin Microbiol,
55(3), 865-876.
Abstract:
Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages.
The diarrheal pathogen Clostridium difficile consists of at least six distinct evolutionary lineages. The RT017 lineage is anomalous, as strains only express toxin B, compared to strains from other lineages that produce toxins a and B and, occasionally, binary toxin. Historically, RT017 initially was reported in Asia but now has been reported worldwide. We used whole-genome sequencing and phylogenetic analysis to investigate the patterns of global spread and population structure of 277 RT017 isolates from animal and human origins from six continents, isolated between 1990 and 2013. We reveal two distinct evenly split sublineages (SL1 and SL2) of C. difficile RT017 that contain multiple independent clonal expansions. All 24 animal isolates were contained within SL1 along with human isolates, suggesting potential transmission between animals and humans. Genetic analyses revealed an overrepresentation of antibiotic resistance genes. Phylogeographic analyses show a North American origin for RT017, as has been found for the recently emerged epidemic RT027 lineage. Despite having only one toxin, RT017 strains have evolved in parallel from at least two independent sources and can readily transmit between continents.
Abstract.
Author URL.
Cairns MD, Preston MD, Hall CL, Gerding DN, Hawkey PM, Kato H, Kim H, Kuijper EJ, Lawley TD, Pituch H, et al (2017). Correction for Cairns et al. "Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages".
J Clin Microbiol,
55(6).
Author URL.
2016
O'Donoghue C, Solomon K, Fenelon L, Fitzpatrick F, Kyne L (2016). Effect of proton pump inhibitors and antibiotics on the gut microbiome of hospitalised older persons.
J Infect,
72(4), 498-500.
Author URL.
2014
Fox EM, Solomon K, Moore JE, Wall PG, Fanning S (2014). Phylogenetic profiles of in-house microflora in drains at a food production facility: comparison and biocontrol implications of Listeria-positive and -negative bacterial populations.
Appl Environ Microbiol,
80(11), 3369-3374.
Abstract:
Phylogenetic profiles of in-house microflora in drains at a food production facility: comparison and biocontrol implications of Listeria-positive and -negative bacterial populations.
Listeria species experience complex interactions with other microorganisms, which may promote growth and colonization of the organism in local environments or negatively affect them. This study investigated the microbial community at a food production facility, examining interactions between Listeria and the associated microbiome. Listeria species can be transferred between zones in the production environment by individuals or equipment, and drains may act as a reservoir for the organism, reflecting the microbial flora potentially in the production environment. Drains that were colonized by Listeria species and those determined to be free of Listeria were examined. In each case, 16S rRNA gene analysis was performed using the PhyloChip platform. Some general similarities in bacterial population structure were observed when Listeria-negative and -positive drain communities were compared, with some distinct differences also noted. These included increased populations of the genera Prevotella and Janthinobacterium associated with the absence of Listeria species, whereas Enterococcus and Rhodococcus were in higher abundance in drains colonized by Listeria species. Based on these results, a selection of bacterial species were grown in coculture biofilm with a Listeria monocytogenes strain identified as having colonized a drain at the facility. Mixed-species biofilm experiments showed that Janthinobacterium inhibited attachment and subsequent biofilm formation of L. monocytogenes; however, Enterococcus gallinarum significantly increased it. The results of this study suggest the microbial community in food processing facilities can impact the colonization of Listeria species and that influencing the microbiome in favor of antilisterial species may reduce the colonization of Listeria species and limit the likelihood of product/process contamination.
Abstract.
Author URL.
2013
Moore P, Kyne L, Martin A, Solomon K (2013). Germination efficiency of clinical Clostridium difficile spores and correlation with ribotype, disease severity and therapy failure.
J Med Microbiol,
62(Pt 9), 1405-1413.
Abstract:
Germination efficiency of clinical Clostridium difficile spores and correlation with ribotype, disease severity and therapy failure.
Spore germination is an important part of the pathogenesis of Clostridium difficile infection (CDI). Spores are resistant to antibiotics, including those therapeutically administered for CDI and strains with a high germination rate are significantly more likely to be implicated in recurrent CDI. The role of germination efficiency in cases of refractory CDI where first-line therapy fails remains unclear. We investigated spore germination efficiencies of clinical C. difficile isolates by measuring drop in OD600 and colony forming efficiency. Ribotype 027 isolates exhibited significantly higher germination efficiencies in the presence of 0.1 % (w/v) sodium taurocholate (51.66 ± 8.75 %; 95 % confidence interval (CI) 47.37-55.95 %) than ribotype 106 (41.91 ± 8.35 %; 95 % CI 37.82-46 %) (P
Abstract.
Author URL.
Solomon K, Martin AJ, O'Donoghue C, Chen X, Fenelon L, Fanning S, Kelly CP, Kyne L (2013). Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses.
J Med Microbiol,
62(Pt 9), 1453-1460.
Abstract:
Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses.
Host anti-toxin immune responses play important roles in Clostridium difficile disease and outcome. The relationship between host immune and inflammatory responses during severe C. difficile infection (CDI) and the risk of mortality has yet to be defined. We aimed to investigate the host systemic IgG anti-toxin immune responses, the in vitro cytotoxicity of the infecting C. difficile ribotyped strain, and the host inflammatory markers and their relationship to CDI disease severity and risk of mortality. Inflammatory markers, co-morbidities and CDI outcomes were recorded in a prospective cohort of 150 CDI cases. Serum anti-cytotoxin a (TcdA) and anti-TcdB IgG titres were measured by ELISA and the infecting C. difficile isolate was ribotyped and the in vitro cytotoxin titre assessed. A low median anti-TcdA IgG titre was significantly associated with 30-day all-cause mortality (P
Abstract.
Author URL.
Solomon K (2013). The host immune response to Clostridium difficile infection.
Ther Adv Infect Dis,
1(1), 19-35.
Abstract:
The host immune response to Clostridium difficile infection.
Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins a and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future.
Abstract.
Author URL.
2012
Solomon K, Kyne L (2012). Clostridium difficile-Associated Colitis: Role of the Immune Response and Approach to Treatment. In (Ed)
Colitis.
Author URL.
Martin A, Solomon K, O'Donoghue C, Hannan M, Fenelon L, Kyne L (2012). Cognitive Impairment Increases Risk of Infection, Recurrence and Death Due to Hospital-onset C. Difficile.
IRISH JOURNAL OF MEDICAL SCIENCE,
181, S229-S229.
Author URL.
Solomon K (2012). Host immune response to C. difficile. European Conference of Clinical Microbiology and Infectious Diseases (ECCMID). 31st Mar - 3rd Apr 2012.
2011
Whyte P, Fanning S, O’Brien S, O’Grady L, Solomon K (2011). 18 Tracing pathogens in red meat and game production chains and at the abattoir. In (Ed) Tracing Pathogens in the Food Chain, 393-432.
Solomon K, Murray S, Scott L, McDermott S, Drudy D, Martin A, O'Donoghue C, Skally M, Burns K, Fenelon L, et al (2011). An investigation of the subtype diversity of clinical isolates of Irish Clostridium difficile ribotypes 027 and 078 by repetitive-extragenic palindromic PCR.
J Med Microbiol,
60(Pt 8), 1080-1087.
Abstract:
An investigation of the subtype diversity of clinical isolates of Irish Clostridium difficile ribotypes 027 and 078 by repetitive-extragenic palindromic PCR.
A repetitive-extragenic palindromic PCR (rep-PCR) subtyping method (DiversiLab) in conjunction with ribotyping, toxinotyping and antimicrobial-susceptibility testing was used to detect subtypes within Clostridium difficile ribotypes 027 and 078. Clinical isolates of ribotypes 027 (toxinotype III) (n = 30) and 078 (toxinotype V) (n = 23) were provided by health-care facilities across the Republic of Ireland over 2 months in 2006 and 1 month in 2009. Ribotype 027 isolates were significantly more related to each other (9 different subtype profiles) when compared to ribotype 078 isolates (14 different profiles) (P = 0.001; cut-off >90 % similarity). Almost half of ribotype 078 isolates (45.5 %) showed no relationship to each other. The clonality of ribotype 027 isolates suggests effective adaptation to the human niche, whereas the considerable genetic diversity within ribotype 078 isolates suggests that they may have originated from a variety of sources. Subtyping correlated well with antimicrobial susceptibility, in particular clindamycin susceptibility for ribotype 027, but diverse antimicrobial-susceptibility profiles were seen in ribotype 078 isolates, even within a single health-care facility. Between 2006 and 2009, a change in the predominant subtype of ribotype 027 was seen, with the recent clone representing half of all ribotype 027 isolates studied. This strain exhibited 89 % similarity to a rep-PCR profile of the North American NAP-1 strain.
Abstract.
Author URL.
Modi N, Gulati N, Solomon K, Monaghan T, Robins A, Sewell HF, Mahida YR (2011). Differential binding and internalization of Clostridium difficile toxin a by human peripheral blood monocytes, neutrophils and lymphocytes.
Scand J Immunol,
74(3), 264-271.
Abstract:
Differential binding and internalization of Clostridium difficile toxin a by human peripheral blood monocytes, neutrophils and lymphocytes.
Colitis due to Clostridium difficile infection is mediated by secreted toxins a and B and is characterized by infiltration by cells from the systemic circulation. The aim of our study was to investigate interactions between fluorescently labelled toxin a and peripheral blood monocytes, neutrophils and lymphocytes. Purified toxin a was labelled with Alexa Fluor® 488 (toxin A(488)) and incubated with isolated human peripheral blood mononuclear cells or washed whole blood cells for varying time intervals at either 37 or 4 °C/ice. The ability of trypan blue to quench cell surface-associated (but not cytoplasmic) fluorescence was also investigated. At 37 °C, toxin A(488) -associated fluorescence in monocytes peaked at 1 h (majority internalized), with subsequent loss associated with cell death. In contrast to monocytes, binding of toxin A(488) in neutrophils was greater on ice than at 37 °C. Studies using trypan blue suggested that over 3 h at 37 °C, most of the toxin A(488)-associated fluorescence in neutrophils remained at the cell surface. Over 48 h (37 °C and ice/4 °C), there was minimal toxin A(488)-associated fluorescence in lymphocytes. These studies suggest major differences in interactions between toxin a and circulating cells that infiltrate the mucosa during colonic inflammation in C. difficile infection.
Abstract.
Author URL.
Solomon K, Fanning S, McDermott S, Murray S, Scott L, Martin A, Skally M, Burns K, Kuijper E, Fitzpatrick F, et al (2011). PCR ribotype prevalence and molecular basis of macrolide-lincosamide-streptogramin B (MLSB) and fluoroquinolone resistance in Irish clinical Clostridium difficile isolates.
J Antimicrob Chemother,
66(9), 1976-1982.
Abstract:
PCR ribotype prevalence and molecular basis of macrolide-lincosamide-streptogramin B (MLSB) and fluoroquinolone resistance in Irish clinical Clostridium difficile isolates.
BACKGROUND: Antimicrobial use is recognized as a risk factor for Clostridium difficile infection (CDI) and outbreaks. We studied the relationship between PCR ribotype, antimicrobial susceptibility and the genetic basis of resistance in response to exposure to antimicrobial agents. METHODS: C. difficile isolates were cultured from 133 CDI patients for whom recent antimicrobial drug exposure had been recorded. Isolates were ribotyped by PCR and assessed for their susceptibility to the macrolide-lincosamide-streptogramin B (MLS(B)) group of compounds (erythromycin and clindamycin) and fluoroquinolone antimicrobials (ciprofloxacin, levofloxacin and moxifloxacin). Where relevant, the genetic basis of resistance was determined. RESULTS: Prevalent ribotypes (including 027, 001 and 106) exhibited significantly greater antimicrobial resistance compared with ribotypes 078 and 014, among others. Clindamycin-resistant ribotype 078 was detected for the first time. Ribotypes 027 and 001 were more likely to exhibit MLS(B) resistance, a feature that was associated with the erm(B) gene. Exposure to MLS(B) or fluoroquinolone antimicrobial compounds in the 8 weeks prior to the onset of infection was not associated with specific genetic markers of resistance. Single amino acid substitutions in the a and B subunits of DNA gyrase were noted and were ribotype specific and linked to resistance to moxifloxacin. CONCLUSIONS: Resistance to MLS(B) and fluoroquinolone antimicrobial compounds is common among prevalent ribotypes of C. difficile. The genetic basis for antimicrobial resistance appears to be ribotype specific and conserved in the absence of recent antimicrobial selection pressure.
Abstract.
Author URL.
2010
Burns K, Skally M, Solomon K, Scott L, McDermott S, O'Flanagan D, Fanning S, Kyne L, Fenelon L, Fitzpatrick F, et al (2010). Clostridium difficile infection in the Republic of Ireland: results of a 1-month national surveillance and ribotyping project, March 2009.
Infect Control Hosp Epidemiol,
31(10), 1085-1087.
Author URL.
Gulati N, Modi N, Solomon K, Robins A, Mahida YR (2010). Differential binding and internalisation of Clostridium difficile toxin a by human peripheral blood monocytes, neutrophils and lymphocytes.
Author URL.
Whyte P, O’Grady L, O’Brien S, Fanning S, Solomon K (2010). Tracing pathogens in red meat and game production chains and at the abattoir. In Brul S, Fratamico PM, McMeekin TA (Eds.)
Tracing Pathogens in the Food Chain, Elsevier, 393-432.
Abstract:
Tracing pathogens in red meat and game production chains and at the abattoir.
Abstract.
2008
Solomon K, Robins A, Mahida YR (2008). Cell surface binding and internalisation of clostridium difficile toxin a by human intestinal epithelial cells.
Author URL.
Sutton PA, Li S, Webb J, Solomon K, Brazier J, Mahida YR (2008). Essential role of toxin a in C. difficile 027 and reference strain supernatant-mediated disruption of Caco-2 intestinal epithelial barrier function.
Clin Exp Immunol,
153(3), 439-447.
Abstract:
Essential role of toxin a in C. difficile 027 and reference strain supernatant-mediated disruption of Caco-2 intestinal epithelial barrier function.
Clostridium difficile induces mucosal inflammation via secreted toxins a and B and initial interactions between the toxins and intestinal epithelial cells (which lead to loss of barrier function) are believed to be important in disease pathogenesis. Secreted toxin-specific antibodies may inhibit such interactions. Using the Caco-2 epithelial cell line, we have investigated the use of an anti-toxin a monoclonal antibody (ATAA) in providing protection against toxin A-mediated disruption of epithelial barrier function (assessed by measurement of transepithelial electrical resistance and luminal to basolateral flux of labelled dextran). In contrast to free antibody, ATAA conjugated to sepharose beads was more effective in neutralizing the activity of purified toxin A. Sepharose bead-conjugated ATAA was subsequently used to investigate the contribution of toxin a in epithelial injury mediated by C. difficile supernatant samples (containing toxins A, B and other products). Loss of barrier function mediated by apical application of supernatant samples of reference and epidemic 027 strains of C. difficile was abrogated by neutralization of toxin A. However, this was not the case when the supernatant samples were applied to the basal surface of epithelial monolayers. In conclusion, our studies have shown that (i) sepharose bead-conjugated ATAA is more effective in neutralizing toxin a than free antibody and (ii) when the apical (luminal) surface of epithelial monolayers is exposed to the secretory products of reference and 027 strains of C. difficile, toxin a is required for the initial injury that leads to loss of barrier function.
Abstract.
Author URL.
2005
Solomon K, Webb J, Ali N, Robins RA, Mahida YR (2005). Monocytes are highly sensitive to clostridium difficile toxin A-induced apoptotic and nonapoptotic cell death.
Infect Immun,
73(3), 1625-1634.
Abstract:
Monocytes are highly sensitive to clostridium difficile toxin A-induced apoptotic and nonapoptotic cell death.
In this study we investigated the in vitro responses of peripheral blood mononuclear preparations and purified monocytes to Clostridium difficile toxin A. In contrast to the responses of T and B cells, exposure to toxin a led to a rapid loss of monocytes in a time- and dose-dependent fashion (the majority of cells were lost within 24 h of exposure to >100 ng of toxin per ml). Transmission electron microscopy, flow cytometry, and fluorescence microscopy after propidium iodide and Hoechst staining showed that cell death in purified preparations of monocytes following exposure to 100 and 1,000 ng of toxin a per ml occurred by apoptosis. Further studies showed that 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazole-carbocyanine iodide aggregates were retained within toxin A-exposed monocyte mitochondria, but cytochrome c was released, suggesting that the apoptotic cascade was triggered in the absence of mitochondrial permeability transition. There was also an increase in caspase-3 activity in toxin A-stimulated monocytes. Following exposure to very high concentrations of toxin a (30 microg/ml), monocyte cell death was predominantly of the necrotic type, with rapid extracellular release of lactate dehydrogenase. These studies demonstrated that C. difficile toxin a has a cell-specific effect, in which monocytes exhibit greater susceptibility than lymphocytes and their death is induced in a concentration-dependent manner.
Abstract.
Author URL.
2004
Johal SS, Hammond J, Solomon K, James PD, Mahida YR (2004). Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy.
Gut,
53(5), 673-677.
Abstract:
Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy.
OBJECTIVES: Clostridium difficile associated diarrhoea (CDAD) is a hospital acquired infection in which optimal methods for diagnosis and the scale of the problem in the community remain to be determined. In hospitalised patients with CDAD, we aimed to (i) study patients in whom the onset of diarrhoea was in the community and (ii) investigate the role of bedside flexible sigmoidoscopy in diagnosis. METHODS: Patients with CDAD (onset in hospital or community) were studied prospectively. In those with diarrhoea of unknown aetiology, flexible sigmoidoscopy was compared with stool assay for C difficile cytotoxin. RESULTS: of 136 patients with CDAD (which was associated with antibiotic exposure in 96%), diarrhoea started in the community in 38 (28%; majority in own home) and while an inpatient in 98 (72%). The majority with CDAD onset in the community had been hospitalised over the preceding 12 months (86.8% v 57.1% in the hospital onset group; p
Abstract.
Author URL.
Johal SS, Solomon K, Dodson S, Borriello SP, Mahida YR (2004). Differential effects of varying concentrations of clostridium difficile toxin a on epithelial barrier function and expression of cytokines.
J Infect Dis,
189(11), 2110-2119.
Abstract:
Differential effects of varying concentrations of clostridium difficile toxin a on epithelial barrier function and expression of cytokines.
BACKGROUND: Presentation after Clostridium difficile infection may depend on the level of epithelial exposure to toxins. We investigated epithelial barrier function and expression of interleukin (IL)-8 and transforming growth factor (TGF)-beta in response to varying concentrations of C. difficile toxin A. METHODS: T84 cells were either preexposed or continuously exposed to C. difficile toxin a (0.01-1000 ng/mL). Barrier function was assessed by measurements of transepithelial electrical resistance. RESULTS: Preexposure to < or =10 ng/mL toxin a led to an increase in the release of TGF-beta 1, but there was no change in the expression of IL-8. In contrast, after preexposure to >10 ng/mL toxin A, there was enhanced expression of IL-8, but release of TGF-beta 1 was similar to that in control monolayers. After preexposure to >10 ng/mL toxin A, there was complete and irreversible loss of electrical resistance. At lower concentrations, loss of resistance across monolayers was followed by recovery, which was enhanced by all 3 recombinant isoforms of TGF-beta. Pretreatment with recombinant isoforms of TGF-beta or coculture with TGF-beta 3-expressing colonic subepithelial myofibroblasts was also protective. CONCLUSIONS: in C. difficile infection, the development and severity of colonic inflammation may depend on the exposure of intestinal epithelial cells to toxins and the expression of proinflammatory (IL-8) and protective (TGF-beta) factors.
Abstract.
Author URL.
2003
Solomon K, Robins RA, Mahida YR (2003). C difficile toxin a induces rapid and selective monocyte cell death.
Author URL.
2002
Johal SS, Solomon K, Webb J, Dodson S, Mahida YR (2002). Changes in epithelial barrier and cytokine release in response to C-difficile toxin A.
GUT,
50, A70-A70.
Author URL.