Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0519030 (Klebsiella)
 21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality in premature infants. Both human surgical specimens and animal models suggest a potential involvement of Paneth cells in NEC pathogenesis. Paneth cells play critical roles in epithelial homeostasis, innate immunity and host-microbial interactions. Yet, the complex interplay between Paneth cell disruption, epithelial barrier dysfunction and microbial-driven inflammation remains unclear in the immature intestine. In this study, mucosal intestinal injury consistent with human NEC was induced in postnatal day 14-16 (P14-P16) mice by disrupting Paneth cells, followed by gavage with Klebsiella pneumonia. Mucosal injury was determined by histology, serum cytokine levels and epithelial barrier dysfunction. Toll-like receptor 4 (TLR4) activation was examined using protein expression, gene expression, and TLR4-/- mice. Finally, the role of bacteria was evaluated using heat-killed bacteria, conditioned media, Bacillus cereus and cecal slurries. We found that live bacteria were required to induce injury; however, TLR4 activation was not required. NEC induced by Paneth cell disruption results in altered localization of tight junction proteins and subsequent loss of barrier function. Prior research has shown a requirement for TLR4 activation to induce NEC-like damage. However, many infants develop NEC in the absence of Gram-negative rod bacteremia, raising the possibility that alternative pathways to intestinal injury exist. In this study, we show a previously unknown mechanism for the development of intestinal injury equivalent to that seen in human NEC and that is not dependent on TLR4 pathways. These data are congruent with the new hypothesis that NEC may be the consequence of several disease processes ending in a final common inflammatory pathway.
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PMID:Paneth-cell-disruption-induced necrotizing enterocolitis in mice requires live bacteria and occurs independently of TLR4 signaling. 2845 Apr 72

Synthetic biology emerges as a powerful approach for unlocking the potential of cyanobacteria to produce various chemicals. However, the highly oxidative intracellular environment of cyanobacteria is incompatible to numerous introduced enzymes from anaerobes. In this study, we explore a strategy based on natural compartmentalization of cyanobacterial heterocysts to overcome the incompatibility. Hence, the oxygen-sensitive 1,3-propanediol (1,3-PDO) biosynthetic pathway was selected as a model and insulated in heterocysts to evaluate the proposed strategy. Thus, the genes from different sources for 1,3-PDO production were tandemly arrayed with promoter, resulting the assembled 1,3-PDO synthetic cassettes. Then the synthetic cassettes were integrated into the chromosome of Anabaena sp. strain PCC7120 by homologous recombination, respectively. The engineered strain P11 containing the genes from facultative anaerobe Klebsiella pneumoniae (cassette KP) accumulated 46.0 mg L-1 of 1,3-PDO when heterocysts were present, which is approximately 1.7-fold higher than that of no heterocysts. As for the strains (P12, P13, and P14) containing the genes from strictly anaerobic bacterium Clostridium butyricum (cassette CB), the product 1,3-PDO could only be detected when heterocysts were present. These results indicate that insulation of the oxygen-sensitive 1,3-PDO pathway with heterocysts is an effective way to protect these enzymes in cyanobacteria. The strategy may have the potential of serving as a universal strategy to overcome the incompatibility of oxygen-sensitivity in synthetic biology.
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PMID:Enhancing Light-Driven 1,3-Propanediol Production by Using Natural Compartmentalization of Differentiated Cells. 3023 72