These authors equally contributed to this work.

MUC2 mucin is a large glycoprotein produced by goblet cells that forms the protective mucus blanket overlying the intestinal epithelium as the first line of innate host defense. High MUC2 production in inflammatory bowel disease and infectious colitis depletes goblet cells and the mucus layer by an unknown mechanism. Herein, we analyzed the effect of high MUC2 biosynthesis on endoplasmic reticulum (ER) stress and apoptosis in goblet cells using a high MUC2-producing human goblet cell line (HT29-H) and an HT29-H clone (HT29-L) silenced for MUC2 expression by lentivirus-mediated shRNA. Goblet cell ER stress and apoptosis were quantified during early onset of dextran sulfate sodium-induced colitis in C57BL/6 and Math1 mice. Compared with HT29-L and MUC2 nonproducing Caco-2 cells, high MUC2-producing HT29-H cells had significantly increased ER stress and apoptosis after treatment with ER stress-inducing agents. Apoptosis was driven by increased misfolded MUC2 that triggered elevated levels of reactive oxygen species. Correcting MUC2 folding and inhibiting reactive oxygen species alleviated ER stress and rescued cells from apoptosis. During early-onset colitis, mucus hypersecretion caused severe ER stress and apoptosis of goblet cells that preceded absorptive epithelial cell damage. Thus, in gastrointestinal inflammation, high MUC2 biosynthesis and goblet cell apoptosis lead to a dysfunctional epithelial barrier. Enhancing MUC2 folding may help alleviate goblet cell depletion and maintain mucosal integrity.

BackgroundMicroorganisms have provided a wealth of metabolites with interesting activities such as antimicrobial, antiviral and anticancer. In this study, a total of 119 aquatic microbial isolates from 30 samples (taken from water bodies in Ghana) were screened by the agar-well diffusion method for ability to produce antibacterial-metabolites.ResultsAntibacterial activity was exhibited by 27 of the isolates (14 bacteria, 9 actinomycetes and 4 fungi) against at least one of the indicator microorganisms: Enterococcus faecalis (ATCC 29212), Bacillus thuringiensis (ATCC 13838), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), Proteus vulgaris (NCTC 4635) and Bacillus Subtilis (NCTC 10073). A sea isolate MAI2 (identified as a strain of Pseudomonas aeruginosa) exhibited the highest antibacterial activity (lowest zone of inhibition = 22 mm). The metabolites of MAI2 extracted with chloroform were stable to heat and gave minimum inhibitory concentrations ranging between 250 and 2000 μg/ml. Bioautography of the extract revealed seven active components.ConclusionThis study has therefore uncovered the potential of water bodies in the West African sub-region as reservoirs of potent bioactive metabolite producing microorganisms.