Table of Contents
Spotlight
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MinireviewRole of β2 Integrins in Neutrophils and SepsisSepsis remains medically challenging, with high morbidity and mortality. A novel intervention is urgently needed in the absence of specific, targeted therapy. Neutrophils act as double-edged swords in sepsis; they can help to eradicate microbes, but they also contribute to tissue injury. β2 integrins are critical adhesion molecules that regulate a number of neutrophil functions. β2 integrins consist of four members, namely, αLβ2, αMβ2,...
Molecular Pathogenesis
Molecular PathogenesisFunctional Properties of Helicobacter pylori VacA Toxin m1 and m2 VariantsHelicobacter pylori colonizes the gastric mucosa and secretes a pore-forming toxin (VacA). Two main types of VacA, m1 and m2, can be distinguished by phylogenetic analysis. Type m1 forms of VacA have been extensively studied, but there has been relatively little study of m2 forms. In this study, we generated...
Molecular Pathogenesis | SpotlightEnterococcus faecalis Manganese Exporter MntE Alleviates Manganese Toxicity and Is Required for Mouse Gastrointestinal ColonizationBacterial pathogens encounter a variety of nutritional environments in the human host, including nutrient metal restriction and overload. Uptake of manganese (Mn) is essential for Enterococcus faecalis growth and virulence; however, it is not known how this organism prevents Mn toxicity. In this study, we examine the role of the highly conserved MntE transporter in...
Molecular PathogenesisThe ESX-1 Virulence Factors Downregulate miR-147-3p in Mycobacterium marinum-Infected MacrophagesAs important virulence factors of Mycobacterium tuberculosis, EsxA and EsxB not only play a role in phagosome rupture and M. tuberculosis cytosolic translocation but also function as modulators of host immune responses by modulating numerous microRNAs (miRNAs). Recently, we have found that...
Molecular PathogenesisDual Function of Aar, a Member of the New AraC Negative Regulator Family, in Escherichia coli Gene ExpressionEnteroaggregative Escherichia coli (EAEC) is an E. coli pathotype associated with diarrhea and growth faltering. EAEC virulence gene expression is controlled by the autoactivated AraC family transcriptional regulator, AggR. AggR activates transcription of a large number of virulence genes, including...
Molecular PathogenesisVibrio cholerae OmpR Contributes to Virulence Repression and Fitness at Alkaline pHVibrio cholerae is a Gram-negative human pathogen and the causative agent of the life-threatening disease cholera. V. cholerae is a natural inhabitant of marine environments and enters humans through the consumption of contaminated food or water. The ability to transition between aquatic ecosystems...
Molecular PathogenesisA Peptidoglycan Amidase Activator Impacts Salmonella enterica Serovar Typhimurium Gut InfectionSalmonella enterica serovar Typhimurium is an important foodborne pathogen that causes diarrhea. S. Typhimurium elicits inflammatory responses and colonizes the gut lumen by outcompeting the microbiota. Although evidence is accumulating with regard to the underlying mechanism, the infectious stage...
Molecular PathogenesisIdentification of Pathogenicity Island Genes Associated with Loss of Type IV Secretion Function during Murine Infection with Helicobacter pyloriChronic Helicobacter pylori colonization in animal models often leads to downregulation of the type IV secretion system (T4SS), typically by recombination in cagY, which is an essential T4SS gene. However, 17 other cag pathogenicity island (cagPAI) genes, as well as some non-cagPAI genes, are also essential for T4SS function. To get...
Molecular PathogenesisEirA Is a Novel Protein Essential for Intracellular Replication of Coxiella burnetiiThe zoonotic bacterial pathogen Coxiella burnetii is the causative agent of Q fever, a febrile illness which can cause a serious chronic infection. C. burnetii is a unique intracellular bacterium which replicates within host lysosome-derived vacuoles. The ability of...
Molecular PathogenesisMycoplasma bovis Membrane Protein MilA Is a Multifunctional Lipase with Novel Lipid and Glycosaminoglycan Binding ActivityThe survival, replication, and virulence of mycoplasmas depend on their ability to capture and import host-derived nutrients using poorly characterized membrane proteins. Previous studies on the important bovine pathogen Mycoplasma bovis demonstrated that the amino-terminal end of an immunogenic 226-kDa (P226) protein, encoded by milA (the full-length product...
Molecular PathogenesisThe Lon-1 Protease Is Required by Borrelia burgdorferi To Infect the Mammalian HostBorrelia burgdorferi encodes a functional homolog of canonical Lon protease termed Lon-2. In addition, B. burgdorferi encodes a second Lon homolog called Lon-1. Recent studies suggest that Lon-1 may function differently from the prototypical Lon protease. However, the function of Lon-1 in...
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Cellular Microbiology: Pathogen-Host Cell Molecular InteractionsApoptosis Functions in Defense against Infection of Mammalian Cells with Environmental ChlamydiaeApoptotic cell death can be an efficient defense reaction of mammalian cells infected with obligate intracellular pathogens; the host cell dies and the pathogen cannot replicate. While this is well established for viruses, there is little experimental support for such a concept in bacterial infections. All Chlamydiales are obligate intracellular bacteria, and different species infect vastly different hosts....
Bacterial Infections
Bacterial Infections | SpotlightUrsodeoxycholic Acid (UDCA) Mitigates the Host Inflammatory Response during Clostridioides difficile Infection by Altering Gut Bile AcidsClostridioides difficile infection (CDI) is associated with increasing morbidity and mortality posing an urgent threat to public health. Recurrence of CDI after successful treatment with antibiotics is high, thus necessitating discovery of novel therapeutics against this enteric pathogen. Administration of the secondary bile acid ursodeoxycholic acid (UDCA; ursodiol)...
Bacterial InfectionsDisruption of Phosphate Homeostasis Sensitizes Staphylococcus aureus to Nutritional ImmunityTo control infection, mammals actively withhold essential nutrients, including the transition metal manganese, by a process termed nutritional immunity. A critical component of this host response is the manganese-chelating protein calprotectin. While many bacterial mechanisms for overcoming nutritional immunity have been identified, the intersection between metal starvation and other essential inorganic nutrients has not been...
Bacterial InfectionsRole of Pseudomonas aeruginosa Glutathione Biosynthesis in Lung and Soft Tissue InfectionThe opportunistic pathogen Pseudomonas aeruginosa is a leading cause of morbidity and mortality worldwide. To survive in both the environment and the host, P. aeruginosa must cope with redox stress. In P. aeruginosa, a primary...
Host Response and Inflammation
Host Response and InflammationMice Lacking γδ T Cells Exhibit Impaired Clearance of Pseudomonas aeruginosa Lung Infection and Excessive Production of Inflammatory CytokinesPseudomonas aeruginosa is an opportunistic pathogen that causes chronic and life-threatening infections in immunocompromised patients. A better understanding of the role that innate immunity plays in the control of P. aeruginosa infection is crucial for therapeutic development. Specifically, the...
Host Response and Inflammation | SpotlightAging Dampens the Intestinal Innate Immune Response during Severe Clostridioides difficile Infection and Is Associated with Altered Cytokine Levels and Granulocyte MobilizationClostridioides (formerly Clostridium) difficile is the most common cause of hospital-acquired infection, and advanced age is a risk factor for C. difficile infection. Disruption of the intestinal microbiota and immune responses contribute to host susceptibility and severity of C...
Fungal and Parasitic Infections
Fungal and Parasitic InfectionsResolvin D1 Administration Is Beneficial in Trypanosoma cruzi InfectionChagas disease is a major public health issue, affecting ∼10 million people worldwide. Transmitted by a protozoan named Trypanosoma cruzi, this infection triggers a chronic inflammatory process that can lead to cardiomyopathy (Chagas disease). Resolvin D1 (RvD1) is a novel proresolution lipid mediator whose effects on inflammatory diseases dampens pathological...
Microbial Immunity and Vaccines
Microbial Immunity and VaccinesCombination of Mycobacterium indicus pranii and Heat-Induced Promastigotes Cures Drug-Resistant Leishmania Infection: Critical Role of Interleukin-6-Producing Classical Dendritic CellsThe major issues in available therapeutic modalities against leishmaniasis are cost, toxicity, and the emergence of drug resistance. The aim of this work was to develop a successful therapeutic adjuvant against drug-resistant Leishmania donovani infection by means of combining Mycobacterium indicus pranii with heat-induced promastigotes (HIP). One-month...
Host-Associated Microbial Communities
Host-Associated Microbial CommunitiesChlamydia Deficient in Plasmid-Encoded pGP3 Is Prevented from Spreading to Large IntestineThe cryptic plasmid pCM is critical for chlamydial colonization in the gastrointestinal tract. Nevertheless, orally inoculated plasmid-free Chlamydia sp. was still able to colonize the gut. Surprisingly, orally inoculated Chlamydia sp. deficient in only plasmid-encoded pGP3 was no longer able to colonize the gut. A comparison of live organism recoveries from individual gastrointestinal tissues revealed that pGP3-...
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