Editorial
Spotlight
Molecular Pathogenesis
Molecular PathogenesisBimodal Response to Shiga Toxin 2 Subtypes Results from Relatively Weak Binding to the Target CellThere are two major antigenic forms of Shiga toxin (Stx), Stx1 and Stx2, which bind the same receptor and act on the same target but nonetheless differ in potency. Stx1a is more toxic to cultured cells, but Stx2 subtypes are more potent in animal models. To understand this phenomenon in cultured cells, we used a system that combines flow cytometry with a fluorescent reporter to monitor the Stx-induced inhibition of protein synthesis in...
Molecular PathogenesisProduction and Uptake of Distinct Endogenous Catecholate-Type Siderophores Are Required for Iron Acquisition and Virulence in Chromobacterium violaceumBacteria use siderophores to scavenge iron from environmental or host sources. The iron acquisition systems of Chromobacterium violaceum, a ubiquitous environmental bacterium that can cause infections in humans, are still unknown. In this work, we demonstrated that C. violaceum produces putative...
Molecular PathogenesisMgrA Negatively Impacts Staphylococcus aureus Invasion by Regulating Capsule and FnbAVirulence genes are regulated by a complex regulatory network in Staphylococcus aureus. Some of the regulators are global in nature and affect many downstream genes. MgrA is a multiple-gene regulator that has been shown to activate genes involved in capsule biosynthesis and repress surface protein genes. The goal of this study was to demonstrate the biological...
Molecular PathogenesisThe scfCDE Operon Encodes a Predicted ABC Importer Required for Fitness and Virulence during Group A Streptococcus Invasive InfectionAs a strict human pathogen, Streptococcus pyogenes (group A Streptococcus, or GAS) causes a wide range of infections, from superficial to life-threatening diseases, upon dissemination. Thus, it is necessary to gain a better understanding of how GAS successfully overcomes host-mediated challenges and infects various host niches.
Molecular Pathogenesis | SpotlightThe Rho-Independent Transcription Terminator for the porA Gene Enhances Expression of the Major Outer Membrane Protein and Campylobacter jejuni Virulence in Abortion InductionCampylobacter jejuni is a leading cause of foodborne illnesses worldwide. Its porA gene encodes the major outer membrane protein (MOMP) that is abundantly expressed and has important physiological functions, including a key role in systemic infection and abortion induction in pregnant animals. Despite the importance of porA in...
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsThe Distinct Immune-Stimulatory Capacities of Porphyromonas gingivalis Strains 381 and ATCC 33277 Are Determined by the fimB Allele and Gingipain ActivityThe Porphyromonas gingivalis strain ATCC 33277 (33277) and 381 genomes are nearly identical. However, strain 33277 displays a significantly diminished capacity to stimulate host cell Toll-like receptor 2 (TLR2)-dependent signaling and interleukin-1β (IL-1β) production relative to 381, suggesting that there are strain-specific differences in one or more bacterial...
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsRole of Supramolecule ErpY-Like Lipoprotein of Leptospira in Thrombin-Catalyzed Fibrin Clot Inhibition and Binding to Complement Factors H and I, and Its Diagnostic PotentialLeptospirosis is one of the most widespread zoonoses caused by pathogenic Leptospira spp. In this study, we report that the LIC11966/ErpY-like lipoprotein is a surface-exposed outer membrane protein exclusively present in pathogenic species of Leptospira. The recombinant ErpY (rErpY)-like protein is recognized by the immunoglobulins of confirmed leptospirosis sera of diverse hosts (human, bovine, and canine),...
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsComparison of Pathogenicity of Invasive and Carried Meningococcal Isolates of ST-4821 Complex in ChinaSerotype 4821 (ST-4821) clonal complex (cc4821) Neisseria meningitidis strains are divided into two groups (groups I and II) according to the core genome-based phylogenetic analysis. Group I contains the greater number of invasive disease isolates. However, the differences in pathogenicity between the two groups are unclear.
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsDuring the Early Stages of Staphylococcus aureus Biofilm Formation, Induced Neutrophil Extracellular Traps Are Degraded by Autologous ThermonucleaseStaphylococcus aureus extracellular DNA (eDNA) plays a crucial role in the structural stability of biofilms during bacterial colonization; on the contrary, host immune responses can be induced by bacterial eDNA. Previously, we observed production of S. aureus thermonuclease during the early stages...
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsPseudomonas aeruginosa ExsA Regulates a Metalloprotease, ImpA, That Inhibits Phagocytosis of MacrophagesPseudomonas aeruginosa is an opportunistic pathogenic bacterium whose type III secretion system (T3SS) plays a critical role in acute infections. Translocation of the T3SS effectors into host cells induces cytotoxicity. In addition, the T3SS promotes the intracellular growth of P. aeruginosa during...
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsExpression of the Nontypeable Haemophilus influenzae Type IV Pilus Is Stimulated by Coculture with Host Respiratory Tract Epithelial CellsThe type IV pilus (Tfp) of nontypeable Haemophilus influenzae (NTHI) mediates adherence, colonization, motility, and biofilm formation, and the major protein subunit, PilA, is a promising vaccine candidate. Thus, it is crucial to understand how Tfp expression is regulated within the microenvironments of the human nasopharynx, which NTHI colonizes asymptomatically, and...
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsModulation of Death and Inflammatory Signaling in Decidual Stromal Cells following Exposure to Group B StreptococcusGroup B Streptococcus (GBS) is an opportunistic bacterial pathogen that contributes to miscarriage, preterm birth, and serious neonatal infections. Studies have indicated that some multilocus sequence types (STs) of GBS are more likely to cause severe disease than others. We hypothesized that the ability of GBS to elicit varying host responses in maternal decidual tissue during pregnancy is an important factor regulating...
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsThe Acinetobacter baumannii Znu System Overcomes Host-Imposed Nutrient Zinc LimitationAcinetobacter baumannii is an opportunistic bacterial pathogen capable of causing a variety of infections, including pneumonia, sepsis, wound, and burn infections. A. baumannii is an increasing threat to public health due to the prevalence of multidrug-resistant strains, leading the World Health...
Bacterial Infections
Bacterial InfectionsCoxiella burnetii Intratracheal Aerosol Infection Model in Mice, Guinea Pigs, and Nonhuman PrimatesCoxiella burnetii, the etiological agent of Q fever, is a Gram-negative bacterium transmitted to humans by inhalation of contaminated aerosols. Acute Q fever is often self-limiting, presenting as a febrile illness that can result in atypical pneumonia. In some cases, Q fever becomes chronic, leading to endocarditis that can be life threatening. The formalin-...
Bacterial InfectionsInteraction Differences of the Avian Host-Specific Salmonella enterica Serovar Gallinarum, the Host-Generalist S. Typhimurium, and the Cattle Host-Adapted S. Dublin with Chicken Primary MacrophageMost Salmonella serovars cause disease in many host species, while a few serovars have evolved to be host specific. Very little is known about the mechanisms that contribute to Salmonella host specificity. We compared the interactions between chicken primary macrophages (CDPM) and host-generalist serovar Salmonella enterica serovar Typhimurium, host-...
Bacterial InfectionsEffect of Phosphatase Activity of the Control of Virulence Sensor (CovS) on Clindamycin-Mediated Streptolysin O Production in Group A StreptococcusSevere manifestations of group A Streptococcus (GAS) infections are associated with massive tissue destruction and high mortality. Clindamycin (CLI), a bacterial protein synthesis inhibitor, is recommended for treating patients with severe invasive GAS infection. Nonetheless, the subinhibitory concentration of CLI induces the production of GAS virulent exoproteins,...
Bacterial InfectionsIdentification of Host Adaptation Genes in Extraintestinal Pathogenic Escherichia coli during Infection in Different HostsExtraintestinal pathogenic Escherichia coli (ExPEC) is an important human and animal pathogen. Despite the apparent similarities in their known virulence attributes, some ExPEC strains can cross the host species barrier and present a zoonotic potential, whereas other strains exhibit host specificity, suggesting the existence of unknown mechanisms that remain to be...
Bacterial InfectionsAntibodies Specific to Membrane Proteins Are Effective in Complement-Mediated Killing of Mycoplasma bovisThe metabolic inhibition (MI) test is a classic test for the identification of mycoplasmas, used for measuring the growth-inhibiting antibodies directed against acid-producing mycoplasmas, although their mechanism still remains obscure. To determine the major antigens involved in the immune killing of Mycoplasma bovis, we used a pulldown assay with anti-...
Bacterial InfectionsDirect Microscopic Observation of Human Neutrophil-Staphylococcus aureus Interaction In Vitro Suggests a Potential Mechanism for Initiation of Biofilm Infection on an Implanted Medical DeviceThe ability of human neutrophils to clear newly attached Staphylococcus aureus bacteria from a serum-coated glass surface was examined in vitro using time-lapse confocal scanning laser microscopy. Quantitative image analysis was used to measure the temporal change in bacterial biomass, neutrophil motility, and fraction of the surface area policed by...
Host Response and Inflammation
Host Response and InflammationImpact of Interleukin-27p28 on T and B Cell Responses during ToxoplasmosisInterleukin-27 (IL-27) is a heterodimeric cytokine composed of the subunits IL-27p28 and EBi3, and while the IL-27 heterodimer influences T cell activities, there is evidence that IL-27p28 can have EBi3-independent activities; however, their relevance to infection is unclear. Therefore, the studies presented here compared how IL-27p28 transgenics and IL-27p28−/− mice responded to the intracellular parasite...
Host Response and InflammationSplenic Innate B1 B Cell Plasmablasts Produce Sustained Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-3 Cytokines during Murine Malaria InfectionsThe physiopathology of malaria, one of the most deadly human parasitic diseases worldwide, is complex, as it is a systemic disease involving multiple parasitic stages and hosts and leads to the activation of numerous immune cells and release of inflammatory mediators.
Host Response and InflammationParticles from the Echinococcus granulosus Laminated Layer Inhibit CD40 Upregulation in Dendritic Cells by Interfering with Akt ActivationThe larval stage of the cestode Echinococcus granulosus causes cystic echinococcosis in humans and livestock. This larva is protected by the millimeter-thick, mucin-based laminated layer (LL), from which materials have to be shed to allow parasite growth. We previously reported that dendritic cells (DCs) respond to microscopic pieces of the mucin gel of the LL (pLL) with unconventional maturation phenotypes, in the absence or...
Host Response and InflammationIn Staphylococcus aureus, the Particulate State of the Cell Envelope Is Required for the Efficient Induction of Host Defense ResponsesUpon microbial infection, host immune cells recognize bacterial cell envelope components through cognate receptors. Although bacterial cell envelope components function as innate immune molecules, the role of the physical state of the bacterial cell envelope (i.e., particulate versus soluble) in host immune activation has not been clearly defined.
Host Response and Inflammationl-Serine Lowers the Inflammatory Responses during Pasteurella multocida InfectionPasteurella multocida causes a variety of infectious diseases in various species of mammals and birds, resulting in enormous economic loss to the modern livestock and poultry industry. However, the mechanism of host-pathogen interaction is unclear. Here, we found that l-serine levels were significantly decreased in murine lungs infected with...
Host Response and InflammationCellular Immune Response against Nontypeable Haemophilus influenzae Infecting the Preinflamed Middle Ear of the Junbo MouseNontypeable Haemophilus influenzae (NTHi) is a major pathogen causing acute otitis media (AOM). The pathology of AOM increases during long-term infection in the middle ear (ME), but the host cellular immune response to bacterial infection in this inflamed environment is poorly understood. Using the Junbo mouse, a characterized NTHi infection model, we...
Host Response and InflammationLipopolysaccharides from Different Burkholderia Species with Different Lipid A Structures Induce Toll-Like Receptor 4 Activation and React with Melioidosis Patient SeraLipopolysaccharides (LPSs) of Gram-negative bacteria comprise lipid A, core, and O-polysaccharide (OPS) components. Studies have demonstrated that LPSs isolated from the pathogenic species Burkholderia pseudomallei and Burkholderia mallei and from less-pathogenic species, such as...
Host Response and InflammationChanges in the Molecular and Functional Phenotype of Bovine Monocytes during Theileria parva InfectionTheileria parva is the causative agent of East Coast fever (ECF), a tick-borne disease that kills over a million cattle each year in sub-Saharan Africa. Immune protection against T. parva involves a CD8+ cytotoxic T cell response to parasite-infected cells. However, there is currently a...
Host Response and InflammationTransbronchial Invasion and Proliferation of Leptospira interrogans in Lung without Inflammatory Cell Infiltration in a Hamster ModelLeptospirosis caused by pathogenic Leptospira is one of the most common zoonoses in the world. It is believed that humans become infected with it mainly through their skin and mucous membranes by contact with water or soil that is contaminated with urine excreted from infected animals. Recently, outbreaks have frequently occurred in the tropics, especially after flooding, but how leptospires cause mass infection remains poorly...
Fungal and Parasitic Infections
Fungal and Parasitic InfectionsAscorbate-Dependent Peroxidase (APX) from Leishmania amazonensis Is a Reactive Oxygen Species-Induced Essential Enzyme That Regulates VirulenceThe molecular mechanisms underlying biological differences between two Leishmania species that cause cutaneous disease, L. major and L. amazonensis, are poorly understood. In L. amazonensis, reactive oxygen species (ROS)...
Fungal and Parasitic InfectionsEntamoeba histolytica Interaction with Enteropathogenic Escherichia coli Increases Parasite Virulence and Inflammation in AmebiasisEpidemiological studies suggest frequent association of enteropathogenic bacteria with Entamoeba histolytica during symptomatic infection. In this study, we sought to determine if the interaction with enteropathogenic (EPEC) or nonpathogenic Escherichia coli (strain DH5α) could modify the virulence...
Fungal and Parasitic InfectionsAssociation of TRAF1/C5 Locus Polymorphisms with Epilepsy and Clinical Traits in Mexican Patients with NeurocysticercosisNeurocysticercosis is caused by the establishment of Taenia solium cysts in the central nervous system. Murine cysticercosis by Taenia crassiceps is a useful model of cysticercosis in which the complement component 5 (C5) has been linked to infection resistance/permissiveness.
Fungal and Parasitic InfectionsCytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4)- and Programmed Death 1 (PD-1)-Mediated Regulation of Monofunctional and Dual Functional CD4+ and CD8+ T-Cell Responses in a Chronic Helminth InfectionChronic helminth infections are known to be associated with the modulation of antigen-specific T-cell responses. Strongyloides stercoralis infection is characterized by the downmodulation of antigen-specific Th1 and Th17 responses and the upregulation of Th2 and Th9 responses. Immune homeostasis is partially maintained by negative regulators of T-cell activation,...
Fungal and Parasitic InfectionsDigital Design of a Universal Rat Intraoral Device for Therapeutic Evaluation of a Topical Formulation against Candida-Associated Denture StomatitisCandida-associated denture stomatitis (DS) is a persistent and chronic oral infection of the denture-bearing palatal mucosa. DS stems from the ability of the fungal opportunistic pathogen Candida albicans to adhere to denture material and invade palatal tissue. Although DS is the most prevalent form of oral candidiasis, there are currently no feasible...
Fungal and Parasitic InfectionsTaurine Alleviates Schistosoma-Induced Liver Injury by Inhibiting the TXNIP/NLRP3 Inflammasome Signal Pathway and PyroptosisSchistosomiasis is a parasitic helminth disease that can cause severe inflammatory pathology, leading to organ damage, in humans. During a schistosomal infection, the eggs are trapped in the host liver, and products derived from eggs induce a polarized Th2 cell response, resulting in granuloma formation and eventually fibrosis.
Microbial Immunity and Vaccines
Microbial Immunity and Vaccines | SpotlightEhrlichia chaffeensis Outer Membrane Protein 1-Specific Human Antibody-Mediated Immunity Is Defined by Intracellular TRIM21-Dependent Innate Immune Activation and Extracellular NeutralizationAntibodies are essential for immunity against Ehrlichia chaffeensis, and protective mechanisms involve blocking of ehrlichial attachment or complement and Fcγ-receptor-dependent destruction. In this study, we determined that major outer membrane protein 1 (OMP-19) hypervariable region 1 (HVR1)-specific human monoclonal antibodies (huMAbs) are protective through...
Microbial Immunity and VaccinesThe Combinations Chitosan-Pam3CSK4 and Chitosan-Monophosphoryl Lipid A: Promising Immune-Enhancing Adjuvants for Anticaries Vaccine PAcWe previously demonstrated that recombinant protein PAc could be administered as an anticaries vaccine. However, the relatively weak immunogenicity of PAc limits its application. In the present study, we investigated the effect of two adjuvant combinations of chitosan plus Pam3CSK4 (chitosan-Pam3CSK4) and of chitosan plus monophosphoryl lipid A (chitosan-MPL) in the immune responses to the PAc...
Microbial Immunity and VaccinesGenome-Wide Identification of Virulence Genes in Erysipelothrix rhusiopathiae: Use of a Mutant Deficient in a tagF Homolog as a Safe Oral Vaccine against Swine ErysipelasSwine erysipelas is caused by the Gram-positive pathogen Erysipelothrix rhusiopathiae. The swine erysipelas live vaccine in Japan, the E. rhusiopathiae Koganei 65-0.15 strain (Koganei), has been reported to cause arthritis and endocarditis. To develop a vaccine with increased safety, we used a virulent Fujisawa strain to construct transposon mutants for a...
Microbial Immunity and VaccinesCritical Role of B Cells in Toll-Like Receptor 7-Mediated Protection against Listeria monocytogenes InfectionToll-like receptors (TLR) trigger the immune system to mount a rapid innate response capable of protecting the host from a wide variety of bacterial and viral pathogens. There is interest in harnessing TLR agonists to reduce the susceptibility of at-risk populations to infection. However, the widespread prophylactic use of TLR agonists has been compromised by the need to administer them by parenteral injection.
Host-Associated Microbial Communities
Host-Associated Microbial CommunitiesResolution and Cooccurrence Patterns of Gardnerella leopoldii, G. swidsinskii, G. piotii, and G. vaginalis within the Vaginal MicrobiomeGardnerella vaginalis is a hallmark of vaginal dysbiosis, but it is found in the microbiomes of women with and without vaginal symptoms and those who do not have microbiologically defined dysbiosis. G. vaginalis encompasses diverse taxa differing in attributes that are potentially important for...
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