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• Low oxygen tensions are present throughout the gastrointestinal tract. • Although Clostridioides difficile is considered as obligate anaerobe, this bacterium can tolerate low oxygen tensions. • Clostridioides difficile oxygen tolerance involves O 2 -reductases that scavenge and detoxify oxygen. • ơB and PerR are key actors of the adaptive response to oxygen. While the gut is typically thought of as anoxic, there are two intersecting and decreasing oxygen gradients that are observed in the gut: oxygen decreases from the small to the large intestine and from the intestinal epithelium toward the colon lumen. Gut oxygen levels also increase following antibiotic induced-dysbiosis. While dysbiosis favors growth of Clostridioides difficile , the oxygen increase also causes stress to this anaerobic enteropathogen. To circumvent oxygen threat, C. difficile has developed efficient strategies: sporulation, biofilm formation, the rerouting of central metabolism and the production of oxygen detoxification enzymes. Especially, reverse rubrerythrins and flavodiiron proteins involved in oxygen reduction are crucial in C. difficile ability to tolerate and survive the oxygen concentrations encountered in the gastrointestinal tract. Two regulators, σB and PerR, play pivotal role in the mastering of these adaptive responses by controlling the various systems that protect cells from oxidative damages. [ABSTRACT FROM AUTHOR]

Many bacterial flagella are specifically O-glycosylated with nonulosonic acids, including the sialic acid derivatives, pseudaminic acid or legionaminic acid. Unlike protein glycosyltransferases that are extracytoplasmic, flagellin glycosyltransferases (fGTs) act cytoplasmically with unknown donor or acceptor specificities. The recent reconstitution of fGT-based glycosylation in heterologous hosts enables analyses underpinning such specificity. [ABSTRACT FROM AUTHOR]

Unidirectional growth of filamentous protein assemblies including the bacterial flagellum relies on dedicated polymerization factors (PFs). The molecular determinants and structural transitions imposed by PFs on multi-subunit assembly are poorly understood. Here, we unveil FlaY from the polarized α-proteobacterium Caulobacter crescentus as a defining member of an alternative class of specialized flagellin PFs. Unlike the paradigmatic FliD capping protein, FlaY relies on a funnel-like β-propeller fold for flagellin polymerization. FlaY binds flagellin and is secreted by the flagellar secretion apparatus, yet it can also promote flagellin polymerization exogenously when donated from flagellin-deficient cells, serving as a transferable, extracellular public good. While the surge in FlaY abundance precedes bulk flagellin synthesis, FlaY-independent filament assembly is enhanced by mutation of a conserved region in multiple flagellin paralogs. We suggest that FlaYs are (multi-)flagellin PFs that evolved convergently to FliDs yet appropriated the versatile β-propeller fold implicated in human diseases for chaperone-assisted filament assembly. [Display omitted] • The FlaY β-propeller protein promotes multi-flagellin filament assembly in Caulobacter • Extracellular donation of FlaY allows flagellar filament assembly in recipient cells • Mutations in the flagellin D0 domain facilitate FlaY-independent filament assembly Kint and Viollier show that the β-propeller protein FlaY promotes multi-flagellin assembly of the flagellar filament in Caulobacter crescentus. FlaY binds flagellin and is secreted by the flagellar secretion apparatus, but it can also promote flagellin polymerization when donated extracellularly. Mutations in the flagellin D0 domain enable FlaY-independent flagellin polymerization. [ABSTRACT FROM AUTHOR]

In the last decades, treatment of multiple myeloma (MM) has greatly improved due to the introduction of novel agents, including proteasome inhibitors (PI) and immunomodulatory agents (IMiDs). Given their generalized use at diagnosis and at relapse and their proven benefit for the large cohort of MM patients, it is of pivotal importance to also critically evaluate any benefit of these agents in very elderly (> 75 years) and frail patients. This review gives an overview of the benefits and toxicities of the currently available treatments in very elderly MM patients with a focus on first-line treatment. In addition we discuss the role of geriatric assessment to optimize treatment efficacy in the more vulnerable cohort. [ABSTRACT FROM AUTHOR]

How cellular checkpoints couple the orderly assembly of macromolecular machines with cell-cycle progression is poorly understood. The alpha-proteobacterium Caulobacter crescentus assembles a single polar flagellum during each cell cycle. We discovered that the expression of multiple flagellin transcripts is licensed by a translational checkpoint responsive to a dual input signal: a secretion-competent hook-basal-body (HBB) structure and a surge in the FlaF secretion chaperone during cytokinesis, instructed by the cell-cycle program. We find that the unorthodox FljJ flagellin, one of the six flagellin paralogs, acts as a checkpoint linchpin, binding both FlaF and the FlbT translational regulator. FljJ recruits FlbT to inhibit translation at the 5′ untranslated region in other flagellin transcripts before HBB assembly. Once FlaF is synthesized and stabilized, it directs FljJ secretion through the HBB, thereby separating FlbT from its co-activator and relieving translational inhibition. The FlbT/FlaF pair is wide spread and its functional properties are conserved in alpha-proteobacteria, including pathogens. • The FljJ flagellin paralog is secreted but cannot assemble a flagellar homo filament • The secretion chaperone FlaF is required for translation of the structural flagellins • FlbT negatively regulates flagellin translation at the 5′UTR when secretion is blocked • FljJ is a secretion coupler required for FlbT activity and it specifically binds FlbT Ardissone et al. unravel the mechanism of secretion coupling in the Caulobacter crescentus flagellation system that encodes six flagellin paralogs. The FljJ flagellin has adopted a regulatory role, binding the negative regulator FlbT that blocks translation of flagellin transcripts before the flagellar secretion machine exports FljJ to license flagellin synthesis. [ABSTRACT FROM AUTHOR]