The flagellar motor protein FliL forms a scaffold of circumferentially positioned rings required for stator activation.

The flagellar motor stator is an ion channel nanomachine that assembles as a ring of the MotA5MotB2 units at the flagellar base. The role of accessory proteins required for stator assembly and activation remains largely enigmatic. Here, we show that one such assembly factor, the conserved protein FliL, forms an integral part of the Helicobacter pylori flagellar motor in a position that colocalizes with the stator. Cryogenic electron tomography reconstructions of the intact motor in whole wild-type cells and cells lacking FliL revealed that the periplasmic domain of FliL (FliL-C) forms 18 circumferentially positioned rings integrated with the 18 MotAB units. FliL-C formed partial rings in the crystal, and the crystal structure-based full ring model was consistent with the shape of the rings observed in situ. Our data suggest that each FliL ring is coaxially sandwiched between the MotA ring and the dimeric periplasmic MotB moiety of the stator unit and that the central hole of the FliL ring has density that is consistent with the plug/linker region of MotB in its extended, active conformation. Significant structural similarities were found between FliL-C and stomatin/prohibitin/flotillin/HflK/C domains of scaffolding proteins, suggesting that FliL acts as a scaffold. The binding energy released upon association of FliL with the stator units could be used to power the release of the plug helices. The finding that isolated FliL-C forms stable partial rings provides an insight into the putative mechanism by which the FliL rings assemble around the stator units.

The Role of the Interleukin-1 Family in Complications of Prematurity.

Preterm birth is a major contributor to neonatal morbidity and mortality. Complications of prematurity such as bronchopulmonary dysplasia (BPD, affecting the lung), pulmonary hypertension associated with BPD (BPD-PH, heart), white matter injury (WMI, brain), retinopathy of prematurity (ROP, eyes), necrotizing enterocolitis (NEC, gut) and sepsis are among the major causes of long-term morbidity in infants born prematurely. Though the origins are multifactorial, inflammation and in particular the imbalance of pro- and anti-inflammatory mediators is now recognized as a key driver of the pathophysiology underlying these illnesses. Here, we review the involvement of the interleukin (IL)-1 family in perinatal inflammation and its clinical implications, with a focus on the potential of these cytokines as therapeutic targets for the development of safe and effective treatments for early life inflammatory diseases.

The role of interleukin-1 in perinatal inflammation and its impact on transitional circulation.

Preterm birth is defined as delivery at <37 weeks of gestational age (GA) and exposes 15 million infants worldwide to serious early life diseases. Lowering the age of viability to 22 weeks GA entailed provision of intensive care to a greater number of extremely premature infants. Moreover, improved survival, especially at extremes of prematurity, comes with a rising incidence of early life diseases with short- and long-term sequelae. The transition from fetal to neonatal circulation is a substantial and complex physiologic adaptation, which normally happens rapidly and in an orderly sequence. Maternal chorioamnionitis or fetal growth restriction (FGR) are two common causes of preterm birth that are associated with impaired circulatory transition. Among many cytokines contributing to the pathogenesis of chorioamnionitis-related perinatal inflammatory diseases, the potent pro-inflammatory interleukin (IL)-1 has been shown to play a central role. The effects of utero-placental insufficiency-related FGR and in-utero hypoxia may also be mediated, in part, via the inflammatory cascade. In preclinical studies, blocking such inflammation, early and effectively, holds great promise for improving the transition of circulation. In this mini-review, we outline the mechanistic pathways leading to abnormalities in transitional circulation in chorioamnionitis and FGR. In addition, we explore the therapeutic potential of targeting IL-1 and its influence on perinatal transition in the context of chorioamnionitis and FGR.