Bacterial growth and cell division requires precise spatiotemporal regulation of the synthesis and remodelling of the peptidoglycan layer that surrounds the cytoplasmic membrane. GpsB is a cytosolic ...protein that affects cell wall synthesis by binding cytoplasmic mini-domains of peptidoglycan synthases to ensure their correct subcellular localisation. Here, we describe critical structural features for the interaction of GpsB with peptidoglycan synthases from three bacterial species (Bacillus subtilis, Listeria monocytogenes and Streptococcus pneumoniae) and suggest their importance for cell wall growth and viability in L. monocytogenes and S. pneumoniae. We use these structural motifs to identify novel partners of GpsB in B. subtilis and extend the members of the GpsB interactome in all three bacterial species. Our results support that GpsB functions as an adaptor protein that mediates the interaction between membrane proteins, scaffolding proteins, signalling proteins and enzymes to generate larger protein complexes at specific sites in a bacterial cell cycle-dependent manner.
Adherence, colonization, and survival of mycobacteria in host cells require surface adhesins, which are attractive pharmacotherapeutic targets. A large arsenal of pilus and non‐pilus adhesins have ...been identified in mycobacteria. These adhesins are capable of interacting with host cells, including macrophages and epithelial cells and are essential to microbial pathogenesis. In the last decade, several structures of mycobacterial adhesins responsible for adhesion to either macrophages or extra cellular matrix proteins have been elucidated. In addition, key structural and functional information have emerged for the process of mycobacterial adhesion to epithelial cells, mediated by the Heparin‐binding hemagglutinin (HBHA). In this review, we provide an overview of the structural and functional features of mycobacterial adhesins and discuss their role as important biomarkers for diagnostics and therapeutics. Based on the reported data, it appears clear that adhesins are endowed with a variety of different structures and functions. Most adhesins play important roles in the cell life of mycobacteria and are key virulence factors. However, they have adapted to an extracellular life to exert a role in host‐pathogen interaction. The type of interactions they form with the host and the adhesin regions involved in binding is partly known and is described in this review.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Burkholderia species such as B. mallei and B. pseudomallei are bacterial pathogens causing fatal infections in humans and animals (glanders and melioidosis), yet knowledge on their virulence factors ...is limited. While pathogenic effects have been linked to a highly conserved gene locus (bur/mal) in the B. mallei group, the metabolite associated to the encoded polyketide synthase, burkholderic acid (syn. malleilactone), could not explain the observed phenotypes. By metabolic profiling and molecular network analyses of the model organism B. thailandensis, the primary products of the cryptic pathway were identified as unusual cyclopropanol‐substituted polyketides. First, sulfomalleicyprols were identified as inactive precursors of burkholderic acid. Furthermore, a highly reactive upstream metabolite, malleicyprol, was discovered and obtained in two stabilized forms. Cell‐based assays and a nematode infection model showed that the rare natural product confers cytotoxicity and virulence.
Virulence factor: The true effector molecules of a disease‐determining biosynthetic gene cluster from diverse pathogenic bacteria were discovered. Polyketides equipped with a cyclopropanol warhead show high chemical reactivity and strong potency in a eukaryotic infection model Caenorhabditis elegans. The chemical relationships between all the complex polyketides were decrypted.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Some pathogens and pests deliver small RNAs (sRNAs) into host cells to suppress host immunity. Conversely, hosts also transfer sRNAs into pathogens and pests to inhibit their virulence. Although sRNA ...trafficking has been observed in a wide variety of interactions, how sRNAs are transferred, especially from hosts to pathogens and pests, is still unknown. Here, we show that host
cells secrete exosome-like extracellular vesicles to deliver sRNAs into fungal pathogen
These sRNA-containing vesicles accumulate at the infection sites and are taken up by the fungal cells. Transferred host sRNAs induce silencing of fungal genes critical for pathogenicity. Thus,
has adapted exosome-mediated cross-kingdom RNA interference as part of its immune responses during the evolutionary arms race with the pathogen.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
is a dominant pathogen in people with cystic fibrosis (CF) contributing to morbidity and mortality. Its tremendous ability to adapt greatly facilitates its capacity to cause chronic infections. The ...adaptability and flexibility of the pathogen are afforded by the extensive number of virulence factors it has at its disposal, providing
with the facility to tailor its response against the different stressors in the environment. A deep understanding of these virulence mechanisms is crucial for the design of therapeutic strategies and vaccines against this multi-resistant pathogen. Therefore, this review describes the main virulence factors of
and the adaptations it undergoes to persist in hostile environments such as the CF respiratory tract. The very large
genome (5 to 7 MB) contributes considerably to its adaptive capacity; consequently, genomic studies have provided significant insights into elucidating
evolution and its interactions with the host throughout the course of infection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Infection by the bacterium Bordetella pertussis continues to cause considerable morbidity and mortality worldwide. Many current acellular pertussis vaccines include the antigen pertactin, which has ...presumptive adhesive and immunomodulatory activities, but is rapidly lost from clinical isolates after the introduction of these vaccines. To better understand the contributions of pertactin antibodies to protection and pertactin's role in pathogenesis, we isolated and characterized recombinant antibodies binding four distinct epitopes on pertactin. We demonstrate that four of these antibodies bind epitopes that are conserved across all three classical Bordetella strains, and competition assays further showed that antibodies binding these epitopes are also elicited by B. pertussis infection of baboons. Surprisingly, we found that representative antibodies binding each epitope protected mice against experimental B. pertussis infection. A cocktail of antibodies from each epitope group protected mice against a subsequent lethal dose of B. pertussis and greatly reduced lung colonization levels after sublethal challenge. Each antibody reduced B. pertussis lung colonization levels up to 100-fold when administered individually, which was significantly reduced when antibody effector functions were impaired, with no antibody mediating antibody-dependent complement-induced lysis. These data suggest that antibodies binding multiple pertactin epitopes protect primarily by the same bactericidal mechanism, which overshadows contributions from blockade of other pertactin functions. These antibodies expand the available tools to further dissect pertactin's role in infection and understand the impact of antipertactin antibodies on bacterial fitness.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The functional diversity of the mammalian intestinal microbiome far exceeds that of the host organism, and microbial genes contribute substantially to the well-being of the host. However, beneficial ...gut organisms can also be pathogenic when present in the gut or other locations in the body. Among dominant beneficial bacteria are several species of Bacteroides, which metabolize polysaccharides and oligosaccharides, providing nutrition and vitamins to the host and other intestinal microbial residents. These topics and the specific organismal and molecular interactions that are known to be responsible for the beneficial and detrimental effects of Bacteroides species in humans comprise the focus of this review. The complexity of these interactions will be revealed.
Difficulties of in vitro culture and genetic manipulation of
Eimeria tenella
have hindered the screening of virulence factors in this parasite. In this study, the
E. tenella
rhoptry protein 30 ...(EtROP30) was expressed in
Toxoplasma gondii
(RH∆Ku80-EtROP30), and its effect on the proliferation and virulence of parasites was investigated. The results revealed that the expression of EtROP30 had no impact on the invasion and egress processes. However, the RH∆Ku80-EtROP30 strain formed larger plaques compared to the RH∆Ku80, indicating that the EtROP30 expression promotes
T. gondii
proliferation. Furthermore, the RH∆Ku80-EtROP30 strain exhibited greater pathogenicity, resulting in earlier mortality and shorter overall survival time compared to RH∆Ku80. These results imply that EtROP30 expression facilitates parasite intracellular proliferation and virulence in mice, suggesting that EtROP30 might be a candidate virulence factor of
E. tenella.
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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
•Candidalysin is the first peptide toxin identified in any human fungal pathogen.•Candidalysin is critical for Candida albicans mucosal and systemic infections.•Candidalysin activates danger-response ...and damage-protection pathways in host cells.•Candidalysin activates the epidermal growth factor receptor in epithelial cells and the NLRP3 inflammasome in macrophages.•Candidalysin drives neutrophil recruitment and Type 17 immunity.
Candidalysin is a cytolytic peptide toxin secreted by the invasive form of the human pathogenic fungus, Candida albicans. Candidalysin is critical for mucosal and systemic infections and is a key driver of host cell activation, neutrophil recruitment and Type 17 immunity. Candidalysin is regarded as the first true classical virulence factor of C. albicans but also triggers protective immune responses. This review will discuss how candidalysin was discovered, the mechanisms by which this peptide toxin contributes to C. albicans infections, and how its discovery has advanced our understanding of fungal pathogenesis and disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Quorum sensing (QS) is a bacterial communication strategy controlling cells density, biofilm formation, virulence, sporulation, and survival. Since QS is considered a virulence factor in ...drug-resistant pathogenic bacteria, inhibition of QS can contribute to control the spread of these bacteria. We propose in this study to test in silico, 19 natural compounds for their potential to inhibit QS transcriptional regulators of Pseudomonas aeruginosa (LasR and PqsE) and Chromobacterium violaceum (CviR and CviR′). Molecular docking was performed to explore the binding energies between selected compounds, and QS signaling proteins. Additionally, molecular dynamics (MD) simulations of the complexes protein-ligand were tested to evaluate the stability of the complexs throughout the simulation process. The simulation interaction diagram (SID) was achieved to compute the radius of gyration (rGyr), solvent accessible surface area (SASA), intramolecular HBs, molecular surface area (MolSA), and polar surface area (PSA). Additionally, the physicochemical properties, pharmacokinetics, drug-likeness, and toxicity analysis of the best-selected compounds were determined. Among these compounds, catechin and nakinadine B were identified as potent QS antagonists that showed the best XP GScore and stable interaction during molecular dynamic simulation. Catechin interacts with LasR and CviR′ displaying XP GScore −10.969 kcal/mol and −9.936 kcal/mol respectively. Additionally, nakinadine B interacts with PqsE and CviR giving XP GScore −7.442 kcal/mol and −10.34 kcal/mol respectively. RMSD plot analysis showed that both catechin and nakinadine B were stable during 50 ns simulation time with the tested target proteins. The predictive result of toxicity demonstrated that catechin and nakinadine B doesn't induce cytotoxicity, immunotoxicity, carcinogenicity, mutagenicity, hepatotoxicity and were at medium risk for hERG inhibition. Also they were found to be inactive for androgen receptor and aromatase. These results imply that catechin and nakinadine B may be suggested as QS modulators, which may reduce the virulence factors of drug-resistant bacteria.
•Natural compounds (n = 19) were tested in silico to interact with P. aeruginosa and C. violaceum QS signaling proteins.•Molecular docking, molecular dynamics, ADME and toxicity were predicted.•Two compounds, catechin and nakinadine B, were selected based on their lowest XP GScore.•No violation of Lipinski's rules of five for catechin and nakinadine B was found.•Results of MDS support that catechin and nakinadine B may be suggested as QS modulators.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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