Posts Tagged ‘moreover’

Microcins mediate competition among Enterobacteriaceae in the inflamed gut

The Enterobacteriaceae are Gram-negative bacteria and include commensal organisms as well as primary and opportunistic pathogens that are among the leading causes of morbidity and mortality worldwide. Although Enterobacteriaceae often comprise less than 1% of a healthy intestine’s microbiota1, some of these organisms can bloom in the inflamed gut2,3,4,5; indeed, expansion of enterobacteria is a hallmark of microbial imbalance known as “dysbiosis”6. Microcins are small secreted proteins that possess antimicrobial activity in vitro7,8, but whose role in vivo has been unclear. Here we demonstrate that microcins enable the probiotic bacterium Escherichia coli Nissle 1917 (EcN) to limit expansion of competing Enterobacteriaceae (including pathogens and pathobionts) during intestinal inflammation. Microcin-producing EcN limited growth of competitors in the inflamed intestine, including commensal E. coli, adherent-invasive E. coli, and the related pathogen Salmonella enterica. Moreover, only therapeutic administration of the wild-type, microcin-producing EcN to mice previously infected with S. enterica substantially reduced intestinal colonization of the pathogen. Our work provides the first evidence that microcins mediate inter- and intra-species competition among the Enterobacteriaceae in the inflamed gut. Moreover, we show that microcins can be narrow-spectrum therapeutics to inhibit enteric pathogens and reduce enterobacterial blooms.

Catalytic alkylation of remote C–H bonds enabled by proton-coupled electron transfer

Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen–hydrogen (N–H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon–hydrogen (C–H) bond functionalization. In the latter process—a subset of the classical Hofmann–Löffler–Freytag reaction—amidyl radicals remove hydrogen atoms from unactivated aliphatic C–H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon–carbon (C–C) bonds. Here we report an approach that overcomes these limitations by homolysing the N–H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C–H abstraction and radical alkylation steps. This C–H alkylation represents a catalytic variant of the Hofmann–Löffler–Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C–C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using traditional HAT-based approaches.

3D images take you inside a lithium battery

A new technique using MRI offers highly detailed 3D images of the insides of batteries. […]

The post 3D images take you inside a lithium battery appeared first on Futurity.

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