Molecular Microbiology

Wed, 12/23/2020 - 22:06
This paper presents the first evidence of a heterodimer formation between the periplasmic domains of ToxR and ToxS, two main regulators of the cholera causative Vibrio cholerae. The interaction establishes a protection of ToxR against proteolysis. The atomic resolution structure of ToxRp shows an αβ‐fold followed by a long unstructured C‐terminal stretch which plays a significant role in the...
Thu, 12/17/2020 - 22:07
A regulatory circuit indicates the interplay between the major outer membrane porin OmpU, periplasmic stress stimuli and the σE response pathway in Vibrio cholerae. This study reveals a negative feedback regulation resulting in fine‐tuning of the ompU expression level, balancing stress response and survival. Putative factor(s) operating on the negative feedback regulation on ompU expression is...
Thu, 10/22/2020 - 22:09
Vibrio cholerae cytolysin is a potent membrane‐damaging toxin that perforates cell membranes by forming oligomeric β‐barrel pores. We have shown that a key tyrosine residue in the hinge region of the pore‐forming motif plays a crucial role in regulating the oligomeric pore‐formation mechanism of the toxin. Such a regulatory mechanism has not been documented earlier in the structurally‐related β‐...
Thu, 10/15/2020 - 22:09
The most lethal malaria parasite, Plasmodium falciparum, rapidly adapts to acquire drug resistance. For the first time, we report that highly resistant Plasmodium parasites carry additional copies of resistance‐conferring genes separate from the genome, which are known as extra‐chromosomal DNA (ecDNA). This finding provides a new model to study a fundamental mechanism of adaptation that is...
Fri, 10/09/2020 - 22:10
HMP‐P synthase (Thi5) is a critical enzyme in the biosynthesis of thiamine pyrophosphate in yeast. A Thi5 homolog from Legionella pneumophila, which contributes to HMP synthesis in its native host, is an enzyme that binds pyridoxal‐5’‐phosphate and releases HMP when the purified protein is incubated with iron. In a heterologous system Thi5 from Saccharomyces cerevisiae and L. pneumophila have...
Mon, 09/28/2020 - 22:09
The majority of M. tuberculosis infections result in latent tuberculosis where bacteria are dormant and exhibit phenotypic drug tolerance. Mycobacterial cell envelope lipids, or their biosynthetic precursors, are exported from the cytoplasm by MmpL transporters. We showed previously that MmpL11 exports lipids that are important for biofilm formation and non‐replicating persistence, two phenotypes...
Sat, 09/05/2020 - 22:11
We describe a protein secretion system in Gram‐negative bacteria that uses a holin membrane protein in tandem with a cell wall editing enzyme. The pairing of holins from different families with various types of peptidoglycan hydrolases suggests that this secretion pathway evolved multiple times. We propose that the pathway be named the Type 10 Secretion System (TXSS). Summary Gram‐negative...
Wed, 09/02/2020 - 22:09
Sulfane sulfur such as glutathione persulfide (GSSH) is produced from H2S oxidation or from L‐cysteine metabolism. It accumulates inside Pseudomonas aeruginosa PAO1 during the stationary phase of growth, inactivating a repressor to increase the expression of a major multidrug efflux pump. The finding explains why the bacterium is relatively resistant to antibiotics at the stationary phase of...
Sat, 08/15/2020 - 22:10
ES24, but not nitrofurantoin, inhibits SecYEG‐dependent protein transport in bacteria and exhibits anti‐bacterial activity towards various clinically relevant strains. In addition, ES24 affects many other processes important to E. coli, hinting at a multifaceted mode of action of ES24. Summary Eeyarestatin 1 (ES1) is an inhibitor of endoplasmic reticulum (ER) associated protein degradation, Sec61...
Fri, 05/01/2020 - 03:24
Vibrio cholerae, the causative agent of the acute diarrheal disease cholera, is able to thrive in diverse habitats such as natural water bodies and inside human hosts. To ensure their survival, these bacteria rely on chemosensory pathways to sense and respond to changing environmental conditions. These pathways constitute a highly sophisticated cellular control system in Bacteria and Archaea....
Sun, 04/26/2020 - 03:22
Copper is essential, but highly toxic. Direct responses of bacteria to excess copper, collectively termed copper homeostasis systems, are well known, but how copper causes toxicity is unclear. This review summarizes how both direct copper homeostasis responses, and indirect accessory stress‐response pathways are essential to resisting copper toxicity among enterobacteria. Abstract Copper is a...
Thu, 04/09/2020 - 03:19
Our data suggest a model in which L. monocytogenes ΔspxA1 produces less cytochrome bd than wt, generating ROS from the incomplete electron transport chain. This would normally be readily detoxified but ΔspxA1 is deficient in catalase production and is thus more sensitive to peroxide‐mediated toxicity. Therefore, the severe ΔspxA1 aerobic growth defect is the result of increased ROS in the absence...
Wed, 04/08/2020 - 03:21
The membrane‐bound transcription regulator ToxR controls housekeeping and virulence gene expression in V. cholerae. The activity and stability of ToxR strongly depends on its operon partner ToxS, the redox state of its periplasmic cysteine residues and environmental stimuli. Here, ToxR‐ToxR PPIs are key for its activity, which is influenced by ToxS, DNA binding capabilities, bile and the...
Wed, 04/01/2020 - 03:16
The ATP binding cassette (ABC) transporter LptB2FGC extracts LPS from the inner membrane and powers the transport of the glycolipid to the cell surface in Gram‐negative bacteria. Our study shows that changes to the LPS structure and the transporter can affect how the function of the cytoplasmic LptB ATPase is coupled to the extraction of LPS by LptFG by either promoting or interfering with the...
Wed, 03/18/2020 - 03:17
Overlapping transcription between the mRNAs of the neighbouring genes is a common process in bacteria. The resulting paired RNAs are digested genome‐wide by the action of the double‐stranded endoribonuclease RNase III. New examples of gene arrangements where overlapping transcription plays a key role are summarised to explain our current understanding regarding how overlapping transcription may...
Wed, 03/18/2020 - 03:17
The universe of Molecular Microbial Pathogenesis is filled with many female and male stars. But there are two particularly bright shining supernovae‐like stars: the late Stanley Falkow and the very lively and creative Pascale Cossart. These two outstanding luminaries, surrounded by numerous planets, do not only belong to different scientific generations but their splendor also comes from very...
Wed, 03/18/2020 - 03:17
Contrary to other human bacterial pathogens, most strains of the human pathogen L. monocytogenes have preserved along decades susceptibility to the key‐drugs used to treat human infections. L. monocytogenes has a large core‐genome (present in all strains of the species), allowing to adapt to multiple environmental niches without the need of recruiting accessory genes from other species by...
Wed, 03/18/2020 - 03:17
Serovar 4b strains of L. monocytogenes possess galactosylated WTAs and LTAs. We show that two different genes, gtlB and gttB encode two distinct glycosyltransferases required for the galactosylation of LTA and WTA respectively. Deletion of these genes reveals that the galactose decoration on WTA but not LTA is responsible for the surface retention and function of the important virulence factor...
Wed, 02/26/2020 - 03:17
Mycobacteria use type VII secretion systems (T7SSs) to translocate proteins across their diderm cell envelope. We previously showed that the Mycobacterium tuberculosis ESX‐5 T7SS is unable to complement secretion in a Mycobacterium marinum esx‐5 mutant, suggesting species‐specificity in secretion. In this study, we established that a specific domain, i.e. linker 2, of the membrane ATPase EccC5 is...
Wed, 02/26/2020 - 03:17
In Vibrio parahaemolyticus, the iron uptake regulator Fur represses genes involved in iron acquisition and swarming. The Fur regulon also includes a previously uncharacterized regulator fcrX. Overproduction of FcrX, which is a small tetratricopeptide repeat‐containing protein, affects phenotypes in multiple bacterial species. FcrX interacts with V. parahaemolyticus and Escherichia coli Fur....
Sat, 01/25/2020 - 03:16
Many pathogenic bacteria use different types of thermosensors to sense increased temperature once inside the host. In this review, we are describing the identification of protein, DNA and RNA thermosensors that took place around 20 years ago. In particular, we describe the events leading to the discovery of the prfA thermosensor in Listeria monocytogenes (depicted). Abstract An outstanding...
Sat, 01/25/2020 - 03:16
Teichoic acids are a diverse class of molecules on the surface of Gram‐positive bacteria known to play important roles in fitness, virulence and bacteriophage susceptibility. A significant level of structural and constitutional heterogeneity exists within the Listeria genus, and it is this variation which serves as a basis for serotyping. Here, we elaborate on recent findings in the Listeria...
Sat, 01/25/2020 - 03:16
While exposure to high levels of toxic metals such as cadmium and arsenic is only experienced in a handful of special habitats and ecosystems, Listeria and other Gram‐positive bacteria have evolved an impressively diverse array of genetic tools for acquiring enhanced tolerance to such metals. Here we summarize this fascinating collection of resistance determinants in Listeria monocytogenes and...
Fri, 01/17/2020 - 03:15
The CodY protein is a global transcriptional regulator of metabolic and virulence genes in low G + C Gram‐positive bacteria, including pathogenic Listeria monocytogenes. Hundreds of CodY‐binding sites were found in the L. monocytogenes genome at near single‐nucleotide resolution, most of them within genes’ coding sequences. In many cases, CodY appears to bind to two overlapping 15‐nt motifs....
Thu, 11/28/2019 - 03:28
Staphylococcus aureus is able to grow in the presence of high concentrations of NaCl but the exact genetic factors contributing to this are unknown. Using a high‐throughput TN‐seq approach, we identified gene 957 as an important factor for the salt stress resistance in S. aureus. A 957‐mutant was not only salt sensitive but also showed increased peptidoglycan crosslinking, altogether highlighting...
Fri, 11/22/2019 - 03:16
DNA phosphorothioation is widely used in antisense drugs. DNA PT modification also exists in bacteria. Using a purified enzyme complex, we show here for the first time how the inert DNA backbone is activated for the exchanging of oxygen with sulfur. Abstract Phosphorothioation (PT) involves the replacement of a nonbridging phosphate oxygen on the DNA backbone with sulfur. In bacteria, the...
Wed, 10/16/2019 - 03:20
Cobamides are a family of cofactors that are widely‐utilized by diverse organisms, and there are over a dozen variants, including vitamin B12. V. cholerae imports a range of cobamides, but it cannot utilize a variant called pseudocobalamin and instead remodels it through a distinct pathway. Abstract Cobamides are a group of compounds including vitamin B12 that can vary at the lower base position...
Mon, 09/23/2019 - 03:15
SiiA is required for the function of the Salmonella SPI4‐encoded T1SS. Using structural and functional studies, we show that the periplasmic domain of SiiA displays a peptidoglycan (PG)‐binding OmpA‐like fold and that SiiA binds PG in vitro and in vivo, albeit at an acidic pH, only. SiiA in complex with SiiB translocates protons across the inner membrane; however, further studies are needed to...
Fri, 08/16/2019 - 14:50
SiiA is required for the function of the Salmonella SPI4‐encoded T1SS. Using structural and functional studies, we show that the periplasmic domain of SiiA displays a peptidoglycan (PG)‐binding OmpA‐like fold and that SiiA binds PG in vitro and in vivo, albeit at an acidic pH, only. SiiA in complex with SiiB translocates protons across the inner membrane; however, further studies are needed to...
Thu, 08/01/2019 - 06:08
The bacterial pathogen Salmonella Typhimurium invades intestinal epithelial cells. Following invasion, the bacteria can either replicate within a membrane bound vacuole or escape into the cytosol. We show here that SipA, a secreted bacterial protein, facilitates the early survival and/or initiation of replication of cytosolic Salmonella. Summary Salmonella enterica serovar Typhimurium is a...
Tue, 07/23/2019 - 15:28
Myxococcus xanthus displays several social behaviors involving cell‐cell contacts. To understand the role of the lipopolysaccharide (LPS) in these behaviors, we identified key enzymes involved in O‐antigen and LPS biosynthesis: the polyisoprenyl‐phosphate hexose‐1‐phosphate transferase, responsible for priming O‐antigen synthesis, and the O‐antigen ligase. We show that LPS O‐antigen is important...
Mon, 07/08/2019 - 10:44
Vibrio cholerae mutants lacking lytic transglycosylases MltC and RlpA are defective for daughter cell separation. Our results suggest that lytic transglycosylases at the division septum serve as a back‐up mechanism to cleave peptidoglycan strands that cannot be cleared by highly‐regulated amidase activity and to clear peptidoglycan debris that may block the completion of outer‐membrane...
Wed, 06/12/2019 - 07:43
Bacteria use ECF sigma factors to maintain metal homeostasis. They regulate the expression of genes either to import metals under conditions of metal depletion or to reduce toxicity when metal concentrations are excessive. These adaptive mechanisms can be complex, consisting of several proteins with different cell locations, or very simple, consisting of only the sigma factor capable of sensing...
Thu, 05/23/2019 - 09:52
Abstract The general stress response (GSR) allows many bacterial species to react to myriad different stressors. In Alphaproteobacteria, this signaling pathway proceeds through the partner‐switching PhyR‐EcfG sigma‐factor mechanism and is involved in multiple life processes, including virulence in Brucella abortus. To date, details of the alphaproteobacterial GSR signaling pathway have been...
Sat, 05/11/2019 - 10:03
The signaling peptide NprX orchestrates the development of B. thuringiensis during the stationary phase. In the absence of NprX, NprR inhibits sporulation by impairing the phosphorylation of Spo0F‐P; in the presence of NprX, NprR–NprX ensures the survival of the bacteria in the insect cadaver. We show that NprX is imported in the bacteria by two olipeptide permease systems: Opp, known to be...
Thu, 05/09/2019 - 10:29
Campylobacter jejuni helical shape is key to its pathogenesis. Under stress, C. jejuni alters its shape from helical to coccoid. This study characterized C. jejuni bacterial cell wall peptidoglycan changes occurring during coccoid formation and identified a role for the peptidoglycan hydrolases Pgp1 and previously uncharacterized AmiA in the process. In addition, we determined that coccoid C....
Mon, 05/06/2019 - 07:48
How motile bacteria recognize their environment and decide whether to stay or move is a fundamental issue in survival. Here we established the molecular mechanism underlying the intimate relationship between nutrient availability and flagellum‐driven motility in Vibrio vulnificus; dephosphorylated EIIAGlc of the PEP:carbohydrate phosphotransferase system sequesters the flagellar assembly protein...
Thu, 04/04/2019 - 12:58
Alternaria alternata contaminates many crops and fruits. The mold produces a large variety of different mycotoxins, one of which is alternariol and its derivatives. We identified the gene cluster responsible for the biosynthesis. We show that alternariol is a colonization and virulence factor on tomato, apple and citrus. Abstract The filamentous fungus Alternaria alternata is a potent producer...
Tue, 04/02/2019 - 11:02
Bacteria can be social and move in groups. Here, we show that Vibrio parahaemolyticus coordinates motility using the S signal, a cell‐cell signaling molecule that serves as a chemoattractant during swimming and swarming. Two methyl‐accepting chemoreceptors detect this autoinducer. One is necessary for S signal reception by liquid‐grown bacteria, while the other is important for chemotaxis by...
Fri, 03/15/2019 - 15:30
Vibrio cholerae is an aquatic bacterium with the potential to infect humans. This study focuses on the DNA replication and cell division of this bi‐chromosomal bacterium during starvation stress. Surprisingly, cells temporarily restart their DNA replication after a first shut‐down period before finally reaching a state with fully replicated single chromosome sets. Abstract Vibrio cholerae is...
Wed, 02/27/2019 - 14:10
Listeria monocytogenes is a soil bacterium that can infect humans upon ingestion. Numerous genes are known that are specifically expressed during infection, but less is known about genes important for survival in the soil. We identified the first genetic module regulating and mediating resistance against the depsipeptide antibiotic aurantimycin A. This substance is produced by Streptomyces...
Sun, 02/17/2019 - 13:58
Synthetic peptide MciZ is a specific inhibitor of B. subtilis division, sporulation and germination that binds with high affinity to key cell division protein FtsZ, blocking its assembly and the formation of the cytokinetic Z‐ring. MciZ activity extends to other Bacillus, including pathogenic B. cereus – anthracis. MciZ is also recognized by FtsZ from S. aureus and intracellularly expressed...
Thu, 02/14/2019 - 13:14
Schematic showing the mechanisms that contribute to maintenance of the virulence plasmid in Shigella flexneri, indicating the position of its functional TA (ccdAB, gmvAT, and vapBC) and partitioning systems (parAB and stbAB) relative to the origin of replication. We showed previously that the plasmid can integrate into the chromosome Summary Members of the genus Shigella carry a large plasmid...
Wed, 02/13/2019 - 12:03
YadA is an essential virulence factor of Yersinia enterocolitica and Yersinia pseudotuberculosis. It is a well‐studied member of the trimeric autotransporter adhesins (TAAs). TAAs are exported to the bacterial cell surface by a peculiar mechanism called “Type Vc secretion”. In this work, we set out to understand the molecular mechanism of type Vc secretion, and found evidence of a hairpin...
Mon, 02/11/2019 - 13:52
The Cpx envelope stress response senses envelope protein misfolding and is required for virulence of many pathogens, including the murine gastrointestinal pathogen Citrobacter rodentium. Here, we show that the C. rodentium Cpx response promotes expression of numerous envelope‐localized proteases and chaperones – including DegP and DsbA, which are required for host infection – while inhibiting...
Mon, 02/11/2019 - 12:14
Cell‐cell communication called quorum sensing regulates numerous behaviors in bacteria, including bioluminescence, biofilm formation, and virulence. At the epicenter of quorum sensing pathways are the transcriptional regulators that respond to changes in bacterial cell density and accordingly alter gene expression. Here we show that the master quorum sensing transcription factors LuxR/HapR in...
Fri, 02/08/2019 - 11:57
Salmonella enterica genomes, as most other bacterial species, host multiple prophages whose genes can represent up to 5% of the genome content. In this review, we aim at putting into light the multiple genetic interactions that can be weaved between the host and its prophages and between prophages themselves within the host. Summary Thanks to the exponentially increasing number of publicly...
Fri, 02/08/2019 - 11:57
Enteroaggregative Escherichia coli (EAEC) is a commonly isolated human pathogen that causes mucoid diarrhoea. As EAEC virulence is controlled by the AggR master transcription factor, we use RNA‐sequencing to identify the AggR‐regulated genes in the pathogenic EAEC strain 042. We report the structure of several AggR‐dependent promoters in order to understand the mechanism of AggR‐mediated...
Fri, 02/08/2019 - 11:57
GcvB sRNA negatively regulates at least 31 target mRNAs mostly involved in amino acid metabolism in Escherichia coli and Salmonella Typhimurium. Two main regions of GcvB, referred to as R1 and R3, are required to base‐pair with described target mRNAs. Remarkably, SroC, a GcvB sRNA sponge, is of prime importance to release GcvB‐dependent repression in stationary phase of growth and in minimal...
Sun, 02/03/2019 - 11:04
Summary The bacterial envelope is a remarkable and complex compartment of the prokaryotic cell in which many essential functions take place. The article by Herrou and collaborators (Herrou et al., in press), by a clever combination of structural analysis, genetics and functional characterization in free‐living bacterial cells and during infection in animal models, elucidates a new factor,...

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