ABSTRACTIncreased microvascular permeability is a hallmark of sepsis and septic shock. Intestinal mucosal dysfunction may allow translocation of bacteria and their products, thereby promoting sepsis and inflammation. AlthoughStaphylococcus aureusalpha-toxin significantly contributes to sepsis and perturbs the endothelial barrier function, little is known about possible effects ofS. aureusalpha-toxin on human epithelial barrier functions. We hypothesize thatS. aureusalpha-toxin in the blood can impair the intestinal epithelial barrier and thereby facilitate the translocation of luminal bacteria into the blood, which may in turn aggravate a septic condition. Here, we showed that staphylococcal alpha-toxin disrupts the barrier integrity of human intestinal epithelial Caco-2 cells as evidenced by decreased transepithelial electrical resistance (TER) and reduced cellular levels of junctional proteins, such as ZO-1, ZO-3, and E-cadherin. The Caco-2 cells also responded to alpha-toxin with an elevated cytosolic calcium ion concentration ([Ca2+]i), elicited primarily by calcium influx from the extracellular environment, as well as with a significant reduction in TER, which was modulated by intracellular calcium chelation. Moreover, a significantly larger reduction in TER and amounts of the junctional proteins,viz., ZO-3 and occludin, was achieved by basolateral than by apical application of the alpha-toxin. These experimental findings thus support the hypothesis that free staphylococcal alpha-toxin in the bloodstream may cause intestinal epithelial barrier dysfunction and further aggravate the septic condition by promoting the release of intestinal bacteria into the underlying tissues and the blood.
The cause of diarrheal disease is usually determined by screening for several microorganisms by various methods, and sole detection is used to assign the agent as the cause of disease. However, it has become increasingly clear that many infections are caused by coinfections with several pathogens and that the dose of the infecting pathogen is important. We quantified the absolute numbers of enterotoxigenic E. coli (ETEC) and Vibrio cholerae directly in diarrheal fluid. We noted several events where both pathogens were found but also a large dose dependency. In three samples, we found ETEC as the only pathogen sought for. These isolates belonged to globally distributed ETEC clones and were the dominating species in stool with active toxin expression. This suggests that certain superior virulent ETEC lineages are able to outcompete the gut microbiota and be the sole cause of disease and hence need to be specifically monitored.
Enterococcus faecium and Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) were classically clustered into the Lancefield Group D streptococci and despite their taxonomic reclassification still share a similar genetic content and environment. Both species are considered as opportunistic pathogens. E. faecium is often associated with nosocomial bacteraemia, and S. gallolyticus is sporadically found in endocarditis of colorectal cancer patients. In both cases, the source of infection is commonly endogenous with a translocation process that launches through the intestinal barrier. To get new insights into the pathological processes preceding infection development of both organisms, we used an in vitro model with Caco-2 cells to study and compare the adhesion, invasion and translocation inherent abilities of 6 E. faecium and 4 S. gallolyticus well-characterized isolates. Additionally, biofilm formation on polystyrene, collagen I and IV was also explored. Overall results showed that E. faecium translocated more efficiently than S. gallolyticus, inducing a destabilization of the intestinal monolayer. Isolates Efm106, Efm121 and Efm113 (p < .001 compared to Ef222) exhibited the higher translocation ability and were able to adhere 2–3 times higher than S. gallolyticus isolates. Both species preferred the collagen IV coated surfaces to form biofilm but the S. gallolyticus structures were more compact (p = .01). These results may support a relationship between biofilm formation and vegetation establishment in S. gallolyticus endocarditis, whereas the high translocation ability of E. faecium high-risk clones might partially explain the increasing number of bacteraemia.
Aim: To investigate the ability of lactobacilli to persist in the genital area (vagina and labia) of women after the topical application of an ointment containing Lactobacillus gasseri LN40, L. fermentum LN99 and L. rhamnosus LN113. Secondary objectives were to study the presence of Escherichia coli and other contaminants, as well as subjective symptoms in the genital tract. Methods: Eighteen healthy postmenopausal women were randomized to use either the study product or placebo for 10 days. Gynecological examinations, labial and vaginal samplings for bacterial cultivation were performed at baseline (visit 1), after treatment (visit 2), and at a 10-day follow-up (visit 3). LN strains were identified by specific cultivation methods. Subjective symptoms were evaluated by a self-administered questionnaire. Results: The presence of LN99 was shown in 7 out of 8 women in the investigational group at visit 2 (p < 0.001 compared to placebo) and in 5 out of 8 at visit 3 (p < 0.05), whereas the presence of LN113 was shown in 2 out of 8 at visit 2 and in 1 out of 8 at visit 3. Subjective symptoms were significantly reduced (p < 0.01) at visits 2 and 3 for both products. Conclusion: Topical application of a probiotic ointment is feasible to achieve persistence of lactobacilli for at least 10 days.
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