Oxidative damage can have a devastating effect on the structure and activity of proteins, and may even lead to cell death. The sulfur-containing amino acids cysteine and methionine are particularly ...susceptible to reactive oxygen species (ROS) and reactive chlorine species (RCS), which can damage proteins. In this Review, we discuss our current understanding of the reducing systems that enable bacteria to repair oxidatively damaged cysteine and methionine residues in the cytoplasm and in the bacterial cell envelope. We highlight the importance of these repair systems in bacterial physiology and virulence, and we discuss several examples of proteins that become activated by oxidation and help bacteria to respond to oxidative stress.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
Thioredoxins are ubiquitous antioxidant enzymes that play important roles in many health-related cellular processes. As such, the fundamental knowledge of how these enzymes work is of prime ...importance for understanding cellular redox mechanisms and for laying the ground for the development of future therapeutic approaches. Over the past 40 years, a really impressive amount of data has been published on thioredoxins. Here, we review the most significant results that have contributed to our knowledge regarding the structure, the function, and the mechanism of these crucial enzymes.
The envelope of Gram-negative bacteria is a complex compartment that is essential for viability. To ensure survival of the bacterial cells in fluctuating environments, several signal transduction ...systems, called envelope stress response systems (ESRSs), exist to monitor envelope biogenesis and homeostasis. The Cpx two-component system is an extensively studied ESRS in
that is active during exposure to a vast array of stresses and protects the envelope under those harmful circumstances. Overproduction of NlpE, a two-domain outer membrane lipoprotein of unclear function, has been used in numerous studies as a molecular trigger to turn on the system artificially. However, the mechanism of Cpx activation by NlpE, as well as its physiological relevance, awaited further investigation. In this paper, we provide novel insights into the role played by NlpE in the Cpx system. We found that, among all outer membrane lipoproteins in
, NlpE is sufficient to induce Cpx when lipoprotein trafficking is perturbed. Under such conditions, fitness is increased by the presence of NlpE. Moreover, we show that NlpE, through its N-terminal domain, physically interacts with the Cpx sensor kinase CpxA. Our data suggest that NlpE also serves to activate the Cpx system during oxidative folding defects in the periplasm and that its C-terminal domain is involved in the sensing mechanism. Overall, our data demonstrate that NlpE acts as a sentinel for two important envelope biogenesis processes, namely, lipoprotein sorting and oxidative folding, and they further establish NlpE as a bona fide member of the Cpx two-component system.
Bacteria rely on a sophisticated envelope to shield them against challenging environmental conditions and therefore need to ensure correct envelope assembly and integrity. A major signaling pathway that performs this role in Gram-negative species is the Cpx system. An outer membrane lipoprotein of unclear function, NlpE, has long been exploited as a research tool to study Cpx in
, since it triggers this system when overproduced or mislocalized; however, the mechanism and physiological relevance of the NlpE-Cpx connection have awaited further investigation. We elucidate a new function for NlpE by showing that it physically interacts with the Cpx sensor CpxA and acts as a sentinel that specifically monitors two essential envelope biogenesis processes, namely, lipoprotein sorting and oxidative folding.
The envelope of bacteria is a complex multilayered shield that ensures multiple essential functions, including protecting the cell from external assaults. Hence, bacterial cells have evolved ...intricate mechanisms called envelope stress response systems (ESRS) to monitor all kinds of perturbations affecting the integrity of their envelope and to mount an appropriate response to contain or repair the damage. In the model bacterium
, several ESRS are built around a two-component system, in which envelope stress triggers a phosphotransfer between a sensor protein in the inner membrane of the envelope and a response regulator in the cytoplasm. In this review, we focus on two major ESRS in
, the Rcs and Cpx pathways, in which additional proteins not directly involved in the phosphotransfer modulate signal transduction. Both the Rcs and Cpx systems can be turned on by a lipoprotein anchored in the outer membrane, RcsF and NlpE, respectively, providing a molecular connection between the most exterior layer of the envelope and the ground control center in the cytoplasm. Here, we review how these two lipoproteins, which share a striking set of features while being distinct in several aspects, act as sentinels at the front line of the bacterium by sensing and transducing stress to the downstream components of the Rcs and Cpx systems.
Prior research assumes that high-status actors have greater organizational influence than lower-status ones, that is, it is easier for the former to get their ideas and initiatives adopted by the ...organization than it is for the latter. Drawing from the literature on ideology, we posit that the status–influence link is contingent on actors’ ideological position. Specifically, status confers organizational influence to the degree that the focal actor is ideologically mainstream. The more an actor’s ideology deviates from the mainstream the less will her status translate into increased organizational influence. We find support for this hypothesis using data on the work of legislators in the House of Representatives in the United States Congress. By illuminating how and under what conditions status leads to increased influence, this study qualifies and extends current understandings of the role of status in organizations.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Most biological membranes contain a bilayer of phospholipid molecules, whereas the outer membrane of Gram-negative bacteria is an asymmetric bilayer with phospholipids for the inner layer and ...lipopolysaccharide molecules making up the outer layer2. The machineries that assemble the outer membrane and the peptidoglycan must coordinate their actions in time and space for harmonious cell growth and a successful cell-division process. ...the many proteins that act as builders in envelope assembly must, like orchestral musicians, work in synchrony and follow the same tempo so that outer-membrane growth keeps pace with peptidoglycan production. ...peptidoglycan maturation is the maestro of the peptidoglycan-BAM orchestra.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The global public health burden of bacterial antimicrobial resistance (AMR) is intensified by Gram-negative bacteria, which have an additional membrane, the outer membrane (OM), outside of the ...peptidoglycan (PG) cell wall. Bacterial two-component systems (TCSs) aid in maintaining envelope integrity through a phosphorylation cascade by controlling gene expression through sensor kinases and response regulators. In
Escherichia coli
, the major TCSs defending cells from envelope stress and adaptation are Rcs and Cpx, which are aided by OM lipoproteins RcsF and NlpE as sensors, respectively. In this review, we focus on these two OM sensors. β-Barrel assembly machinery (BAM) inserts transmembrane OM proteins (OMPs) into the OM. BAM co-assembles RcsF, the Rcs sensor, with OMPs, forming the RcsF-OMP complex. Researchers have presented two models for stress sensing in the Rcs pathway. The first model suggests that LPS perturbation stress disassembles the RcsF-OMP complex, freeing RcsF to activate Rcs. The second model proposes that BAM cannot assemble RcsF into OMPs when the OM or PG is under specific stresses, and thus, the unassembled RcsF activates Rcs. These two models may not be mutually exclusive. Here, we evaluate these two models critically in order to elucidate the stress sensing mechanism. NlpE, the Cpx sensor, has an N-terminal (NTD) and a C-terminal domain (CTD). A defect in lipoprotein trafficking results in NlpE retention in the inner membrane, provoking the Cpx response. Signaling requires the NlpE NTD, but not the NlpE CTD; however, OM-anchored NlpE senses adherence to a hydrophobic surface, with the NlpE CTD playing a key role in this function.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The cell envelope of gram-negative bacteria constitutes the first protective barrier between a cell and its environment. During host infection, the bacterial envelope is subjected to several ...stresses, including those induced by reactive oxygen species (ROS) and reactive chlorine species (RCS) produced by immune cells. Among RCS,
chlorotaurine (
ChT), which results from the reaction between hypochlorous acid and taurine, is a powerful and less diffusible oxidant. Here, using a genetic approach, we demonstrate that
Typhimurium uses the CpxRA two-component system to detect
-ChT oxidative stress. Moreover, we show that periplasmic methionine sulfoxide reductase (MsrP) is part of the Cpx regulon. Our findings demonstrate that MsrP is required to cope with
-ChT stress by repairing
-ChT-oxidized proteins in the bacterial envelope. By characterizing the molecular signal that induces Cpx when
Typhimurium is exposed to
-ChT, we show that
-ChT triggers Cpx in an NlpE-dependent manner. Thus, our work establishes a direct link between
-ChT oxidative stress and the envelope stress response.
While the ERA5 reanalysis is commonly utilized in climate studies on extratropical cyclones (ETCs), only a few studies have quantified its ability in the representation of ETCs over land. To address ...this gap, this study evaluates ERA5's skill in representing the ETC‐associated 10‐m wind speed and the precipitation in central and eastern North America during 2005–2019. Hourly data collected from ~3000 stations, amounting to around 420 million reports stored in the Integrated Surface Database, is used as reference. For the spatial‐averaged ETC properties, ERA5 shows a good skill for wind speed with normalized mean bias (NMB) of −0.7% and normalized root‐mean‐square error (NRMSE) of 14.3%, despite a tendency to overestimate low winds and underestimate high winds. The ERA5 skill is worse for precipitation than for wind speed with NMB of −10.4% and NRMSE of 56.5% and a strong tendency to underestimate high values. For both variables, the best and worst performance is found in DJF and JJA, respectively. Negative biases are often identified over regions with stronger precipitation/wind speeds, and a systematic underestimation of wind speed is found over the Rockies with complex topography. Compared to the averaged ETCs, ERA5's performance deteriorates for the top 5% extreme ETCs with a stronger tendency to underestimate both wind speed and precipitation (NMB of −10.2% and −22.6%, respectively). Furthermore, ERA5's skill is worse for local extreme values within ETCs than for spatial averages. Our results highlight some important limitations of the ERA5 reanalysis products for studies looking at the possible impacts of ETCs.
This study evaluates the ability of ERA5 to represent 10‐m wind speeds and precipitation associated with extratropical cyclones using station observations in North America. For cyclone‐averaged quantities, ERA5 shows a good skill for wind speed while errors are four times larger for precipitation. ERA5 shows strong limitations to represent local extremes within cyclones for both variables. Overall, ERA5 performs the best and worst in DJF and JJA, respectively.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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