Table of Contents
Editorial
Spotlight
Minireviews
MinireviewAntibodies and Protection in Systemic Salmonella Infections: Do We Still Have More Questions than Answers?Salmonella causes grave systemic infections in humans and other animals and provides a paradigm for other diseases in which the bacteria have both intracellular and extracellular lifestyles. New generations of vaccines rely on the essential contribution of the antibody responses for their protection. The quality, antigen specificity, and functions associated with...
Minireview | SpotlightThe Great ESKAPE: Exploring the Crossroads of Bile and Antibiotic Resistance in Bacterial PathogensThroughout the course of infection, many pathogens encounter bactericidal conditions that threaten the viability of the bacteria and impede the establishment of infection. Bile is one of the most innately bactericidal compounds present in humans, functioning to reduce the bacterial burden in the gastrointestinal tract while also aiding in digestion. It is becoming increasingly apparent that pathogens successfully resist the bactericidal...
Molecular Pathogenesis
Molecular PathogenesisRab5a Promotes Cytolethal Distending Toxin B-Induced Cytotoxicity and InflammationThe cytolethal distending toxin B subunit (CdtB) induces significant cytotoxicity and inflammation in many cell types that are involved in the pathogenesis of postinfectious irritable bowel syndrome (PI-IBS). However, the underlying mechanisms remain unclear. This study tested the potential role of Rab small GTPase 5a (Rab5a) in the process. We tested mRNA and protein expression of proinflammatory cytokines (interleukin-1β [IL-1β] and...
Molecular PathogenesisDiffusible Signal Factors Act through AraC-Type Transcriptional Regulators as Chemical Cues To Repress Virulence of Enteric PathogensSuccessful colonization by enteric pathogens is contingent upon effective interactions with the host and the resident microbiota. These pathogens thus respond to and integrate myriad signals to control virulence. Long-chain fatty acids repress the virulence of the important enteric pathogens Salmonella enterica and...
Molecular Pathogenesis | SpotlightGenome-Wide Mutagenesis Identifies Factors Involved in Enterococcus faecalis Vaginal Adherence and PersistenceEnterococcus faecalis is a Gram-positive commensal bacterium native to the gastrointestinal tract and an opportunistic pathogen of increasing clinical concern. E. faecalis also colonizes the female reproductive tract, and reports suggest vaginal colonization increases following antibiotic treatment...
Molecular PathogenesisGeneration and Characterization of Typhoid Toxin-Neutralizing Human Monoclonal AntibodiesTyphoid toxin is a virulence factor of Salmonella enterica serovar Typhi, the causative agent of typhoid fever, and is thought to be responsible for the symptoms of severe disease. This toxin has a unique A2B5 architecture with two active subunits, the ADP ribosyl transferase PltA and the DNase CdtB, linked to a pentameric B subunit, which is alternatively made of...
Molecular PathogenesisThe Salmonella LysR Family Regulator RipR Activates the SPI-13-Encoded Itaconate Degradation ClusterItaconate is a dicarboxylic acid that inhibits the isocitrate lyase enzyme of the bacterial glyoxylate shunt. Activated macrophages have been shown to produce itaconate, suggesting that these immune cells may employ this metabolite as a weapon against invading bacteria. Here, we demonstrate that in vitro, itaconate can exhibit bactericidal effects under acidic conditions similar to the pH of a macrophage phagosome. In parallel...
Molecular PathogenesisSuppression of Chlamydial Pathogenicity by Nonspecific CD8+ T LymphocytesChlamydia trachomatis, a leading infectious cause of tubal infertility, induces upper genital tract pathology, such as hydrosalpinx, which can be modeled with Chlamydia muridarum infection in mice. Following C. muridarum...
Molecular Pathogenesis | SpotlightPhosphotransferase System Uptake and Metabolism of the β-Glucoside Salicin Impact Group A Streptococcal Bloodstream Survival and Soft Tissue InfectionStreptococcus pyogenes (group A Streptococcus [GAS]), a major human-specific pathogen, relies on efficient nutrient acquisition for successful infection within its host. The phosphotransferase system (PTS) couples the import of carbohydrates with their phosphorylation prior to metabolism and has been linked to GAS pathogenesis. In a screen of an insertional...
Molecular PathogenesisAntibody Binding and Complement-Mediated Killing of Invasive Haemophilus influenzae Isolates from Spain, Portugal, and the NetherlandsHaemophilus influenzae is a Gram-negative bacterium that can be classified into typeable (types a through f) and nontypeable (NTHi) groups. This opportunistic pathogen asymptomatically colonizes the mucosal epithelium of the upper respiratory tract, from where it spreads to other neighboring regions, potentially leading to disease. Infection with NTHi can cause otitis...
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions | SpotlightImmunization against Anaplasma phagocytophilum Adhesin Binding Domains Confers Protection against Infection in the Mouse ModelAnaplasma phagocytophilum causes granulocytic anaplasmosis, a debilitating infection that can be fatal in the immunocompromised. It also afflicts animals, including dogs, horses, and sheep. No granulocytic anaplasmosis vaccine exists. Because A. phagocytophilum is an obligate intracellular bacterium...
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsBrucella abortus and Pregnancy in Mice: Impact of Chronic Infection on Fertility and the Role of Regulatory T Cells in Tissue ColonizationStealthy intracellular bacterial pathogens are known to establish persistent and sometimes lifelong infections. Some of these pathogens also have a tropism for the reproductive system, thereby increasing the risk of reproductive disease and infertility. To date, the pathogenic mechanism involved remains poorly understood. Here, we demonstrate that Brucella abortus, a...
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions | SpotlightMultiple Ehrlichia chaffeensis Genes Critical for Its Persistent Infection in a Vertebrate Host Are Identified by Random Mutagenesis Coupled with In Vivo Infection AssessmentEhrlichia chaffeensis, a tick-transmitted obligate intracellular rickettsial agent, causes human monocytic ehrlichiosis. In recent reports, we described substantial advances in developing random and targeted gene disruption methods to investigate the functions of E. chaffeensis genes. We reported...
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsParacellular Pathway-Mediated Mycoplasma hyopneumoniae Migration across Porcine Airway Epithelial Barrier under Air-Liquid Interface ConditionsMycoplasma hyopneumoniae is an important respiratory pathogen of pigs that causes persistent and secondary infections. However, the mechanisms by which this occurs are unclear. In this study, we established air-liquid interface culture systems for pig bronchial epithelial cells (ALI-PBECs) that were comparable to the conditions in the native bronchus in vivo...
Bacterial Infections
Bacterial InfectionsThe Novel Streptococcal Transcriptional Regulator XtgS Negatively Regulates Bacterial Virulence and Directly Represses PseP TranscriptionStreptococcus agalactiae (group B streptococcus [GBS]) has received continuous attention for its involvement in invasive infections and its broad host range. Transcriptional regulators have an important impact on bacterial adaptation to various environments. Research on transcriptional regulators will shed new light on GBS pathogenesis. In this study, we identified a...
Bacterial InfectionsGenome-Wide Assessment of Streptococcus agalactiae Genes Required for Survival in Human Whole Blood and PlasmaStreptococcus agalactiae (group B streptococcus, or GBS) is a common cause of bacteremia and sepsis in newborns, pregnant women, and immunocompromised patients. The molecular mechanisms used by GBS to survive and proliferate in blood are not well understood. Here, using a highly virulent GBS strain and transposon-directed insertion site sequencing (TraDIS), we...
Bacterial InfectionsLeukocidins and the Nuclease Nuc Prevent Neutrophil-Mediated Killing of Staphylococcus aureus BiofilmsBacterial biofilms are linked with chronic infections and have properties distinct from those of planktonic, single-celled bacteria. The virulence mechanisms associated with Staphylococcus aureus biofilms are becoming better understood. Human neutrophils are critical for the innate immune response to S....
Bacterial InfectionsColonization of the Murine Oropharynx by Streptococcus pyogenes Is Governed by the Rgg2/3 Quorum Sensing SystemStreptococcus pyogenes is a human-restricted pathogen most often found in the human nasopharynx. Multiple bacterial factors are known to contribute to persistent colonization of this niche, and many are important in mucosal immunity and vaccine development. In this work, mice were infected intranasally with transcriptional regulator mutants of the Rgg2/3 quorum...
Host Response and Inflammation
Host Response and InflammationEndocervical miRNA Expression Profiles in Women Positive for Chlamydia trachomatis with Clinical Signs and/or Symptoms Are Distinct from Those in Women Positive for Chlamydia trachomatis without Signs and SymptomsChlamydia trachomatis is the leading cause of sexually transmitted infections that may progress to pelvic inflammatory disease and infertility. No effective vaccine exists for Chlamydia, nor are there biomarkers available that readily predict disease progression. In this cross-sectional pilot study, we recruited symptomatic and asymptomatic women with...
Host Response and Inflammation | SpotlightDifferential Induction of Type I and III Interferons by Staphylococcus aureusStaphylococcus aureus is a leading cause of bacterial pneumonia, and we have shown previously that type I interferon (IFN) contributes to the pathogenesis of this disease. In this study, we screened 75 S. aureus strains for their ability to induce type I and III IFN. Both cytokine pathways were...
Host Response and Inflammation | SpotlightGroup A Streptococcus Infection of the Nasopharynx Requires Proinflammatory Signaling through the Interleukin-1 ReceptorGroup A Streptococcus (GAS) is the etiologic agent of numerous high-morbidity and high-mortality diseases. Infections are typically highly proinflammatory. During the invasive infection necrotizing fasciitis, this is in part due to the GAS protease SpeB directly activating interleukin-1β (IL-1β) independent of the canonical inflammasome pathway. The upper respiratory tract is the primary site for GAS colonization, infection,...
Host Response and InflammationLow-Avidity Autoantibodies against Bactericidal/Permeability-Increasing Protein Occur in Gram-Negative and Gram-Positive BacteremiaAntibody autoreactivity against bactericidal/permeability-increasing protein (BPI) is strongly associated with Pseudomonas aeruginosa infection in cystic fibrosis (CF), non-CF bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD). We examined the pathogen-specific nature of this autoreactivity by examining antibodies to BPI in bacteremia patients....
Fungal and Parasitic Infections
Fungal and Parasitic InfectionsMicroscopic and Submicroscopic Asymptomatic Plasmodium falciparum Infections in Ghanaian Children and Protection against Febrile MalariaNaturally acquired immunity to Plasmodium falciparum malaria is thought to be nonsterile and sustained by persistence of low-level parasitemia. This study assessed the association between baseline microscopic and submicroscopic asymptomatic P. falciparum infections and antimalarial antibody levels...
Fungal and Parasitic InfectionsCharacterization of Extracellular Vesicles from Entamoeba histolytica Identifies Roles in Intercellular Communication That Regulates Parasite Growth and DevelopmentExtracellular vesicles (EVs) secreted by eukaryotic and prokaryotic cells to transport lipids, proteins, and nucleic acids to the external environment have important roles in cell-cell communication through cargo transfer. We identified and characterized EVs from Entamoeba histolytica, a protozoan parasite and a human pathogen. Conditioned medium from amebic parasites...
Fungal and Parasitic InfectionsImportance of the Immunodominant CD8+ T Cell Epitope of Plasmodium berghei Circumsporozoite Protein in Parasite- and Vaccine-Induced ProtectionThe circumsporozoite protein (CSP) builds up the surface coat of sporozoites and is the leading malaria pre-erythrocytic-stage vaccine candidate. CSP has been shown to induce robust CD8+ T cell responses that are capable of eliminating developing parasites in hepatocytes, resulting in protective immunity. In this study, we characterized the importance of the immunodominant CSP-derived epitope SYIPSAEKI of...
Microbial Immunity and Vaccines
Microbial Immunity and Vaccines | SpotlightIntratracheal Inoculation with Brucella melitensis in the Pregnant Guinea Pig Is an Improved Model for Reproductive Pathogenesis and Vaccine StudiesReproductive failure is the hallmark of brucellosis in animals. An uncommon but important complication in pregnant women who become acutely infected with Brucella melitensis is spontaneous pregnancy loss or vertical transmission to the fetus. Unfortunately, the mechanism behind reproductive failure is still obscure, partially due to the lack of a proper study model....
Microbial Immunity and VaccinesVaccination with Secreted Aspartyl Proteinase 2 Protein from Candida parapsilosis Can Enhance Survival of Mice during C. tropicalis-Mediated Systemic CandidiasisThe rising incidence of non-albicans Candida species globally, along with the emergence of drug resistance, is a cause for concern. This study investigated the protective efficacy of secreted aspartyl proteinase 2 (Sap2) in systemic C. tropicalis infection. Vaccination with recombinant Sap2 (rSap2) protein from...
Microbial Immunity and VaccinesComparative Study of Immunogenic Properties of Purified Capsular Polysaccharides from Streptococcus suis Serotypes 3, 7, 8, and 9: the Serotype 3 Polysaccharide Induces an Opsonizing IgG ResponseStreptococcus suis is an encapsulated bacterium and one of the most important swine pathogens and a zoonotic agent for which no effective vaccine exists. Bacterial capsular polysaccharides (CPSs) are poorly immunogenic, but anti-CPS antibodies are essential to the host defense against encapsulated bacteria. In addition to the previously known serotypes 2 and 14, which...
Host-Associated Microbial Communities
Host-Associated Microbial CommunitiesA Role of Epithelial Cells and Virulence Factors in Biofilm Formation by Streptococcus pyogenes In VitroBiofilm formation by Streptococcus pyogenes (group A streptococcus [GAS]) in model systems mimicking the respiratory tract is poorly documented. Most studies have been conducted on abiotic surfaces, which poorly represent human tissues. We have previously shown that GAS forms mature and antibiotic-resistant biofilms on physiologically relevant epithelial cells....
Host-Associated Microbial CommunitiesNiche- and Gender-Dependent Immune Reactions in Relation to the Microbiota Profile in Pediatric Patients with Otitis Media with EffusionOtitis media with effusion (OME) is a common inflammatory disease that primarily affects children. OME is defined as a chronic low-grade inflammation of the middle ear (ME), without any signs of infection and with effusion persisting in the ME for more than 3 months. The precise pathogenesis is, however, not fully understood. Here, we comprehensively characterized and compared the host immune responses (inflammatory cells and mediators...
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