Infection and Immunity

Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) are ESKAPE pathogens that are responsible for severe skin and soft tissue infections (SSTIs), particularly in the elderly and those with immunocompromising conditions. Rising rates of methicillin-resistant S. aureus (MRSA) and carbapenem-resistant PA have rendered standard antibiotics less effective. Unfortunately, there are currently no licensed vaccines for either pathogen. To address this need, we developed a bivalent intranasal (IN)...

The biosynthetic locus encoding the exopolysaccharide poly-N-acetyl-glucosamine (PNAG) is widely conserved across bacteria, including the World Health Organization critical-priority pathogen Klebsiella pneumoniae (Kp). In Kp, PNAG synthesis is mediated by the pgaABCD operon, yet its lineage-specific regulation remains incompletely understood. Using a comparative genomics approach to interrogate the pgaABCD locus across the high-risk clonal Kp complex 258 (CC258) lineage, we identified a...

The ESKAPE group of pathogens comprises Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp., which are capable of developing profound biofilms while infecting host tissues and medical devices. In addition to acting as a barrier to antimicrobial treatments and as a niche for the transmission of antibiotic resistance genes, biofilm-associated extracellular polymeric substances and metabolites modulate innate and...

Curli fibers produced by Escherichia coli are functional amyloids that activate Toll-like receptor 2 (TLR2), initiating innate immune responses at mucosal surfaces. While microbiome-derived curli contribute to host-microbe interactions, their intrinsic immunostimulatory activity limits their utility as programmable scaffolds for engineered probiotic systems, and dysregulated TLR2 activation has been associated with inflammatory bowel disease, systemic lupus erythematosus, neurodegeneration, and...

Enterotoxigenic Escherichia coli (ETEC) remains a leading cause of diarrheal disease in low- and middle-income countries, yet vaccine efforts have struggled to achieve broad and durable protection. To better understand early steps in host-pathogen interactions, we utilized human stem cell-derived jejunal organoid monolayers to compare epithelial responses to ETEC H10407 and E24377A, prototypical strains frequently used in controlled human infection challenges. Transcriptomic analysis revealed...

Coxiella burnetii is an obligate intracellular bacterial pathogen that causes the zoonotic disease Q fever. Coxiella extensively subverts host vesicle traffic and replicates within lysosome-derived, spacious vacuoles by secreting a suite of effectors through the type IVB secretion system (T4BSS). This study investigates the regulation and role of a fundamental lysosomal process, exocytosis, in the prolonged maintenance of Coxiella vacuolar niche. Biochemical, microscopic, and proteomic...

For all pathogenic microbes, metabolic processes are essential for growth, development, and survival during infection. However, host niches are dynamic environments where nutrient availability can vary, and host defense mechanisms often restrict access to host-derived nutrients. Therefore, microbes must adapt to these microenvironments by regulating nutrient acquisition and metabolism, and by employing mechanisms such as virulence factors that release host-derived nutrients. This metabolic...

Giardiasis caused by the intestinal protozoan Giardia lamblia is a major global cause of diarrheal disease and malabsorption particularly affecting young children and populations in low- and middle-income countries. Despite evidence of immunity after infection, no human vaccine is available. Induction of effective mucosal immunity is critical for protection against this lumen-dwelling pathogen, but has been hampered by the lack of suitable adjuvants. We show here in a murine model that cyclic...

Canine and human anaplasmosis are tick-borne diseases caused by the obligate intracellular bacteria, Anaplasma phagocytophilum and Anaplasma platys, respectively. In veterinary medicine, peptides derived from the immunodominant P44 protein are used to detect antibodies in serological point-of-care tests for anaplasmosis. To inform efforts to develop improved chimeric diagnostic proteins for anaplasmosis, the structure of the predicted surface-exposed domain (residues 151-308) of P44 was...

Iron and oxygen availability fluctuate spatially across mammalian tissues as well as temporally during bacterial infection. The [2Fe-2S] cluster-coordinating transcription factor IscR senses changes in iron and oxygen levels and plays a pivotal role in how Yersinia, Salmonella, and Vibrio regulate critical virulence genes, like the type III secretion system (T3SS). We previously showed that clusterless apo-IscR promotes expression of the Yersinia pseudotuberculosis T3SS master regulator LcrF by...

Francisella tularensis is a gram-negative bacterium that causes tularemia, a fatal zoonotic disease. F. tularensis has been used in the bioweapon programs of several countries. Its potential use as a bioterrorism agent led the CDC to classify F. tularensis as a Tier 1 Select Agent. The cytosolic sensor absent in melanoma 2 (Aim2) detects double-stranded DNA in the cytosol of infected cells and subsequently assembles a multiprotein complex known as the inflammasome. Inflammasome activation drives...

Dendritic cells (DCs) require substantial metabolic reprogramming to mount an immune response against parasites. In the context of Echinococcus granulosus infection, parasite antigens can modulate host immune responses; however, their specific impact on DC metabolism remains poorly defined. We measured mitochondrial membrane potential (ΔΨM), intracellular reactive oxygen species (ROS), and nitric oxide (NO) production in FMS-like tyrosine kinase 3 ligand (FLT3-L)-derived DC (FL-DCs) stimulated...

Campylobacter jejuni is a microaerophilic, gram-negative bacterium and one of the leading causes of bacterial gastroenteritis worldwide, most commonly transmitted through contaminated poultry products. The organism exhibits striking host-specific behavior, persisting as a harmless commensal in the chicken intestine while causing inflammatory disease and rapid proliferation in the human gut. Despite its clinical importance, the mechanisms underlying nutrient acquisition, metabolic adaptation, and...

Pseudomonas aeruginosa is a key bacterial pathogen causing lethal infections in the lungs of cystic fibrosis (CF) patients. These infections involve complex interactions between P. aeruginosa and the airway mucosal epithelium, which are regulated by multiple factors including bacterial adhesion. Calcium (Ca^(2+)), a potent cellular signal, the levels of which increase in the airway fluids during CF, was shown to alter the expression of multiple virulence factors in P. aeruginosa. However, its...

Enteric viruses are major causes of gastrointestinal disease worldwide and are primarily transmitted through the fecal-oral route. Upon entering the gastrointestinal tract, these viruses encounter the dense and diverse population of intestinal microbiota, leading to frequent interactions with commensal bacteria. Over the past decade, numerous studies have demonstrated that bacteria can enhance enteric viral replication, stability, and overall pathogenesis. Although direct binding interactions...