Editorial
Spotlight
Minireview
- MinireviewHeat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils
Leishmania, the causative agent of leishmaniasis, is an intracellular pathogen that thrives in the insect gut and mammalian macrophages to complete its life cycle. Apart from temperature difference (26 to 37°C), it encounters several harsh conditions, including oxidative stress, inflammatory reactions, and low pH. Heat shock proteins (HSPs) play essential roles in cell survival by strategically reprogramming cellular processes...
Molecular Pathogenesis
- Molecular PathogenesisThe Role of luxS in Histophilus somni Virulence and Biofilm Formation
S-Ribosylhomocysteinase (LuxS) is required for the synthesis of the autoinducer-2 (AI-2) quorum-sensing signaling molecule in many Gram-negative bacteria. The bovine (and ovine) opportunistic pathogen Histophilus somni contains luxS and forms a biofilm containing an exopolysaccharide (EPS) in the matrix. Since biofilm formation is regulated by quorum...
- Molecular PathogenesisThe Pyocin Regulator PrtR Regulates Virulence Expression of Pseudomonas aeruginosa by Modulation of Gac/Rsm System and c-di-GMP Signaling Pathway
In Pseudomonas aeruginosa, the second messenger cyclic-di-GMP and Gac/Rsm signaling pathways are associated with the transition from acute to chronic infection. Therefore, identification of the molecular mechanisms that govern lifestyle choice in bacteria is very important.
- Molecular PathogenesisThe Yersinia pestis GTPase BipA Promotes Pathogenesis of Primary Pneumonic Plague...
Yersinia pestis is a highly virulent pathogen and the causative agent of bubonic, septicemic, and pneumonic plague. Primary pneumonic plague caused by inhalation of respiratory droplets contaminated with Y. pestis is nearly 100% lethal within 4 to 7 days without antibiotic intervention.
- Molecular PathogenesisBile Salts Differentially Enhance Resistance of Enterohemorrhagic Escherichia coli O157:H7 to Host Defense Peptides
During passage through the human gastrointestinal tract, enterohemorrhagic Escherichia coli (EHEC) is exposed to membrane-damaging bile in the small intestine. We previously reported that EHEC treatment with a physiological bile salt mixture upregulates basRS, encoding a two-component system, and arnBCADTEF, encoding the aminoarabinose lipid A...
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
- Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsMicrobial Lipid A Remodeling Controls Cross-Presentation Efficiency and CD8 T Cell Priming by Modulating Dendritic Cell Function
The majority of Gram-negative bacteria elicit a potent immune response via recognition of lipid A expressed on the outer bacterial membrane by the host immune receptor Toll-like receptor 4 (TLR4). However, some Gram-negative bacteria evade detection by TLR4 or alter the outcome of TLR4 signaling by modification of lipid A species.
- Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsEukaryotic SNARE VAMP3 Dynamically Interacts with Multiple Chlamydial Inclusion Membrane Proteins
Chlamydia trachomatis, an obligate intracellular pathogen, undergoes a biphasic developmental cycle within a membrane-bound vacuole called the chlamydial inclusion. To facilitate interactions with the host cell, Chlamydia modifies the inclusion membrane with type III secreted proteins, called Incs.
- Cellular Microbiology: Pathogen-Host Cell Molecular Interactions | SpotlightcAMP-Independent Activation of the Unfolded Protein Response by Cholera Toxin
Cholera toxin (CT) is an AB5 protein toxin that activates the stimulatory alpha subunit of the heterotrimeric G protein (Gsα) through ADP-ribosylation. Activation of Gsα produces a cytopathic effect by stimulating adenylate cyclase and the production of cAMP.
- Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsAdoptive Transfer of Group 3-Like Innate Lymphoid Cells Restores Mouse Colon Resistance to Colonization of a Gamma Interferon-Susceptible Chlamydia muridarum Mutant
The obligate intracellular bacterium Chlamydia muridarum can colonize the mouse colon for a long period, but a gamma interferon (IFN-γ)-susceptible mutant clone fails to do so. Nevertheless, the mutant’s colonization is rescued in mice deficient in interleukin-7 receptor (IL-7R) (lacking both lymphocytes and innate lymphoid cells [ILCs]) or IFN-γ but not in mice...
- Cellular Microbiology: Pathogen-Host Cell Molecular Interactions(p)ppGpp-Dependent Regulation of the Nucleotide Hydrolase PpnN Confers Complement Resistance in Salmonella enterica Serovar Typhimurium
The stringent response is an essential mechanism of metabolic reprogramming during environmental stress that is mediated by the nucleotide alarmones guanosine tetraphosphate and pentaphosphate [(p)ppGpp]. In addition to physiological adaptations, (p)ppGpp also regulates virulence programs in pathogenic bacteria, including Salmonella enterica serovar Typhimurium. S...
- Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsAcid Ceramidase Rescues Cystic Fibrosis Mice from Pulmonary Infections
Previous studies have shown that sphingosine kills a variety of pathogenic bacteria, including Pseudomonas aeruginosa and Staphylococcus aureus. Sphingosine concentrations are decreased in airway epithelial cells of cystic fibrosis (CF) mice, and this defect has been linked to the infection...
Bacterial Infections
- Bacterial InfectionsCardiotropic Isolates of Listeria monocytogenes with Enhanced Vertical Transmission Dependent upon the Bacterial Surface Protein InlB
Listeria monocytogenes is a facultative Gram-positive intracellular bacterium that is capable of causing serious invasive infections in pregnant women, resulting in abortion, still-birth, and disseminated fetal infection. Previously, a clinical L. monocytogenes isolate, 07PF0776, was identified as...
- Bacterial InfectionsTargeting Neuropilin-1 Suppresses the Stability of CD4+ CD25+ Regulatory T Cells via the NF-κB Signaling Pathway in Sepsis
Neuropilin-1 (Nrp-1) contributes to maintaining the stability of CD4+ CD25+ regulatory T cells (Tregs). We investigated the impact of Nrp-1 on the stability of CD4+ CD25+ Tregs, and the underlying signaling pathways, in a model of sepsis. Splenic CD4+ CD25+ Tregs were either treated with anti-Nrp-1, transfected to silence Nrp-1 and...
- Bacterial InfectionsGastric Metabolomics Detects Helicobacter pylori Correlated Loss of Numerous Metabolites in Both the Corpus and Antrum
Helicobacter pylori is a chronic bacterial pathogen that thrives in several regions of the stomach, causing inflammation that can vary by site and result in distinct disease outcomes. Whether the regions differ in terms of host-derived metabolites is not known. We thus characterized the regional variation of the metabolomes of mouse gastric corpus and antrum organoids...
Host Response and Inflammation
- Host Response and Inflammation | SpotlightExogenous Reproductive Hormones nor Candida albicans Colonization Alter the Near Neutral Mouse Vaginal pH
While human vaginal pH in childbearing-age women is conclusively acidic, the mouse vaginal pH is reported as being near neutral. However, this information appears to be somewhat anecdotal with respect to vulvovaginal candidiasis, as such claims in the literature frequently lack citations of studies that specifically address this physiological factor. Given the disparate pH between mice and humans, the role of exogenous hormones and...
- Host Response and Inflammation | SpotlightCXCR3-Dependent Immune Pathology in Mice following Infection with Toxoplasma gondii during Early Pregnancy
Toxoplasmosis is a worldwide zoonosis caused by the obligate intracellular parasite Toxoplasma gondii. The symptoms of congenital toxoplasmosis range from embryonic death and resorption to subclinical infection, but the mechanism of disease onset remains unclear.
Microbial Immunity and Vaccines
- Microbial Immunity and Vaccines | SpotlightDefining the Mechanistic Correlates of Protection Conferred by Whole-Cell Vaccination against Pseudomonas aeruginosa Acute Murine Pneumonia
Pseudomonas aeruginosa is a Gram-negative pathogen that causes severe pulmonary infections associated with high morbidity and mortality in immunocompromised patients. The development of a vaccine against P. aeruginosa could help prevent infections caused by this highly antibiotic-resistant...
- Microbial Immunity and VaccinesA Chimeric Plasmodium vivax Merozoite Surface Protein Antibody Recognizes and Blocks Erythrocytic P. cynomolgi Berok Merozoites In Vitro
Research on erythrocytic Plasmodium vivax merozoite antigens is critical for identifying potential vaccine candidates in reducing P. vivax disease. However, many P. vivax studies are constrained by its inability to undergo long-...
Commentary
For over three decades, investigators have used estrogen-dependent rodent animal models to study pathogenesis of vulvovaginal candidiasis (VVC) or test promising antifungal drugs. One disparity not well publicized is that rodents maintain near neutral vaginal pH, which is in contrast to the acidic vaginal pH in women.