This study aimed to determine whether allelic variants of the FimH adhesin from Salmonella enterica confer differential bacterial binding to different types of mammalian cells [murine bone marrow-derived dendritic cells (DCs) and HEp-2 cells] and chicken leukocytes. Although the type 1 fimbriated S. enterica serovar Typhimurium strains AJB3 (SR-11 derivative) and SL1344 both aggregated yeast cells, only the former bound efficiently to DCs and HEp-2 cells. Type 1 fimbriaemediated binding to DCs having previously been shown to require the FimH adhesin and to be inhibited by mannose, FimH sequences from strains SL1344 and AJB3 were compared and found to differ by only one residue, asparagine 158 in SL1344 being replaced by a tyrosine in AJB3. The importance of residue 158 for FimH-mediated binding was further confirmed in recombinant Escherichia coli expressing S. enterica type 1 fimbriae with a variety of substitutions engineered at this position. Additional studies with the 'non-adhesive' FimH of a type 2 fimbriated S. enterica serovar Gallinarum showed that this FimH did not mediate bacterial binding to murine DCs or HEp-2 cells. However, the type 2 FimH significantly improved bacterial adhesion to chicken leukocytes, in comparison to the type 1 FimH of strain AJB3, attributing for the first time a function to the type 2 fimbriae of S. enterica. Consequently, our data show that allelic variation of the S. enterica FimH adhesin directs not only host-cell-specific recognition, but also distinctive binding to mammalian or avian receptors. It is most relevant that this allele-specific binding profile parallels the host specificity of the respective FimH-expressing pathogen.

BackgroundProton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) have been widely used as stress ulcer prophylaxis (SUP) in critically ill patients, however, its efficacy and safety remain unclear. This study aimed to assess the effect of SUP on clinical outcomes in critically ill adults.MethodsLiterature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane database of clinical trials for randomized controlled trials (RCTs) that investigated SUP, with PPI or H2RA, versus placebo or no prophylaxis in critically ill patients from database inception through 1 June 2019. Study selection, data extraction and quality assessment were performed in duplicate. The primary outcomes were clinically important gastrointestinal (GI) bleeding and overt GI bleeding. Conventional meta-analysis with random-effects model and trial sequential analysis (TSA) were performed.ResultsTwenty-nine RCTs were identified, of which four RCTs were judged as low risk of bias. Overall, SUP could reduce the incident of clinically important GI bleeding [relative risk (RR) = 0.58; 95% confidence intervals (CI): 0.42–0.81] and overt GI bleeding (RR = 0.48; 95% CI: 0.36–0.63), these results were confirmed by the sub-analysis of trials with low risk of bias, TSA indicated a firm evidence on its beneficial effects on the overt GI bleeding (TSA-adjusted CI: 0.31–0.75), but lack of sufficient evidence on the clinically important GI bleeding (TSA-adjusted CI: 0.23–1.51). Among patients who received enteral nutrition (EN), SUP was associated with a decreased risk of clinically important GI bleeding (RR = 0.61; 95% CI: 0.44–0.85; TSA-adjusted CI: 0.16–2.38) and overt GI bleeding (RR = 0.64; 95% CI: 0.42–0.96; TSA-adjusted CI: 0.12–3.35), but these benefits disappeared after adjustment with TSA. Among patients who did not receive EN, SUP had only benefits in reducing the risk of overt GI bleeding (RR = 0.37; 95% CI: 0.25–0.55; TSA-adjusted CI: 0.22–0.63), but not the clinically important GI bleeding (RR = 0.27; 95% CI: 0.04–2.09).ConclusionsSUP has benefits on the overt GI bleeding in critically ill patients who did not receive EN, however, its benefits on clinically important GI bleeding still needs more evidence to confirm.

Synthesized gene of human thymosin alpha 1 (Tα 1 ) was inserted into pET-28a, pET-9c, pThioHis B, pGEX-2T or pBV222 and then inductively expressed in strains of Escherichia coli. Among the five expression systems, the BL21/pET-28a system provides the highest expression level of fusion protein in a soluble form, which is up to 70% of total expressed bacterial proteins as visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The resulting fusion protein purified through nickel affinity chromatography accounts for 2.53% of the wet bacterial pellet weight and reaches 94.5% purity by SDS-PAGE. These results indicate the potential of this expression system for high-throughput production of recombinant Tα1.

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