Attaching and effacing (A/E) lesion formation by enteropathogenic E. coli on human intestinal mucosa is dependent on non-LEE effectors

Enteropathogenic E. coli (EPEC) is a human pathogen that causes acute and chronic pediatric diarrhea. The hallmark of EPEC infection is the formation of attaching and effacing (A/E) lesions in the intestinal epithelium. Formation of A/E lesions is mediated by genes located on the pathogenicity island locus of enterocyte effacement (LEE), which encode the adhesin intimin, a type III secretion system (T3SS) and six effectors, including the essential translocated intimin receptor (Tir). Seventeen additional effectors are encoded by genes located outside the LEE, in insertion elements and prophages. Here, using a stepwise approach, we generated an EPEC mutant lacking the entire effector genes (EPEC0) and intermediate mutants. We show that EPEC0 contains a functional T3SS. An EPEC mutant expressing intimin but lacking all the LEE effectors but Tir (EPEC1) was able to trigger robust actin polymerization in HeLa cells and mucin-producing intestinal LS174T cells. However, EPEC1 was unable to form A/E lesions on human intestinal in vitro organ cultures (IVOC). Screening the intermediate mutants for genes involved in A/E lesion formation on IVOC revealed that strains lacking non-LEE effector/s have a marginal ability to form A/E lesions. Furthermore, we found that Efa1/LifA proteins are important for A/E lesion formation efficiency in EPEC strains lacking multiple effectors. Taken together, these results demonstrate the intricate relationships between T3SS effectors and the essential role non-LEE effectors play in A/E lesion formation on mucosal surfaces

Laparoscopic correction of perforated peptic ulcer: first choice? A review of literature

Background Perforated peptic ulcer (PPU), despite antiulcer medication and Helicobacter eradication, is still the most common indication for emergency gastric surgery associated with high morbidity and mortality. Outcome might be improved by performing this procedure laparoscopically, but there is no consensus on whether the benefits of laparoscopic closure of perforated peptic ulcer outweigh the disadvantages such as prolonged surgery time and greater expense. Methods An electronic literature search was done by using PubMed and EMBASE databases. Relevant papers written between January 1989 and May 2009 were selected and scored according to Effective Public Health Practice Project guidelines. Results Data were extracted from 56 papers, as summarized in Tables 1-7. The overall conversion rate for laparoscopic correction of perforated peptic ulcer was 12.4%, with main reason for conversion being the diameter of perforation. Patients presenting with PPU were predominantly men (79%), with an average age of 48 years. Onethird had a history of peptic ulcer disease, and one-fifth took nonsteroidal anti-inflammatory drugs (NSAIDs). Only 7% presented with shock at admission. There seems to be no consensus on the perfect setup for surgery and/or operating technique. In the laparoscopic groups, operating time was significant longer and incidence of recurrent leakage at the repair site was higher. Nonetheless there was significant less postoperative pain, lower morbidity, less mortality, and shorter hospital stay. Conclusion There are good arguments that laparoscopic correction of PPU should be first treatment of choice. A Boey score of 3, age over 70 years, and symptoms persisting longer than 24 h are associated with higher morbidity and mortality and should be considered contraindications for laparoscopic intervention