Infection and Immunity

Many Clostridioides difficile strains can form two colony morphotypes: rough and smooth. The rough and smooth morphotypes differ in multiple phenotypes, including cell length and chaining, motility, biofilm production, and virulence in the hamster model of C. difficile infection (CDI). Colony morphology undergoes phase variation and is determined by the ON/OFF expression of cmrRST, which encodes a signal transduction system. Here, we test the hypothesis that differences in colony morphology and...

Chlamydia pneumoniae (Cpn) is an obligate intracellular parasitic pathogen that replicates inside a membrane-bound vacuole termed the inclusion. This compartment is modified by chlamydial inclusion membrane proteins (Incs), which interact with host proteins to facilitate chlamydial development and pathogenicity. Among these, Cpn0308 localizes specifically to the inclusion membrane. Our previous study demonstrated that exogenously expressed Cpn0308 can interact with host protein ACBD3; here, we...

Muco-obstructive airway diseases result in an increase in mucus accumulation and a decrease in mucus clearance. MUC5B is the most abundant secreted mucin in the human airways, and MUC5B mucin strands dimerize to create the mucus mesh network in the healthy respiratory tract. In muco-obstructive airway diseases like cystic fibrosis (CF), immune cells and bacteria release enzymes that degrade MUC5B into smaller fragments that become entangled and compacted, contributing to pathogenesis. We...

Therapeutic strategies that manipulate the host response to infection to reduce inflammation and host driven tissue damage may reduce disease pathogenesis. However, therapeutic approaches that have dual host-modulatory and antimicrobial therapeutic effects remain limited. Mammalian targeting MEK1/2 inhibitor compounds represent one class of small molecules that have now been recognized to have anti-viral effects through disruption of viral replication in epithelial cells and have direct...

TonB-dependent transport systems (consisting of TonB-dependent transporters, TonB, ExbB, and ExbD) facilitate uptake of nutrients across the bacterial outer membrane. Tol-Pal systems contain components related to those of TonB systems. In this study, we investigated TonB-dependent transport systems in Helicobacter pylori. H. pylori genomes contain three tonB paralogs (designated tonB1, tonB2, and tonB3/tolA), three exbB paralogs, three exbD paralogs, six genes encoding putative TonB-dependent...

Human babesiosis is an emerging disease caused by intraerythrocytic Babesia parasites, primarily transmitted through tick bites. Among the species of Babesia that infect humans, Babesia duncani causes severe disease in murine models, associated with excessive cytokine responses that contribute to immunopathology. The parasite factors that mediate host immune activation remain poorly defined. Here, we show that B. duncani, similar to B. microti, exports antigens through vesicle-mediated pathways....

Lyme disease (LD), caused by Borrelia burgdorferi (Bb), is the most common vector-borne disease in the United States. Novel strategies to control transmission of Bb to humans via ticks are critical for the prevention of LD. One such strategy is to leverage non-infectious mutant strains of Bb for pathogen-derived biologics to block Bb transmission during the natural infectious cycle. Deletion of Borrelia host-adaptation Regulator (ΔbadR) and replacement of eight conserved residues with alanines...

Shigella flexneri causes shigellosis, the second leading cause of diarrheal deaths worldwide. The pathogen invades colonic epithelial cells using a type III secretion system (T3SS) that delivers effector proteins to remodel the host actin cytoskeleton. Following invasion, S. flexneri acquires actin-based motility and spreads cell to cell, driving epithelial destruction and bloody diarrhea. These intracellular infection processes have been investigated primarily using exponentially growing...

The goals of this study were to develop a model to study host-pathogen interactions in primary human colon organoids and to test the hypothesis that Bacteroides fragilis toxin (BFT-2) secreted in outer membrane vesicles (OMVs) modulates mucosal immunity and CFTR Cl⁻ secretion. Since Bacteroides species reside in mucus, OMVs are likely to represent a mechanism of communication between Bacteroides and the host. Two strains of Bacteroides were studied: enterotoxigenic Bacteroides fragilis (ETBF),...

Bacterial pathogens must possess finely tuned physiological adaptations to adapt to their infectious niche. One such niche inhabited by Listeria monocytogenes (L. monocytogenes) is the host cell cytosol, a compartment characterized by significant barriers to entry, metabolic limitation, and immune surveillance. Previously, we identified L. monocytogenes transposon mutants defective for intracellular survival due to disruptions in key metabolic pathways, including cell wall biosynthesis,...

Klebsiella pneumoniae makes up 85% of carbapenem-resistant Enterobacteriaceae, bacteria that have become an urgent threat to public health. K. pneumoniae is largely transmitted in healthcare settings, where inpatients and outpatients are often anesthetized with the widely used anesthetic induction agent propofol. Recent evidence obtained from rodent infection models indicates that propofol exposure can dramatically increase host susceptibility to microbial infections. Given that intensive care...

Sulfur modification of tRNAs enhances translational accuracy and efficiency, yet its contribution to bacterial pathogenesis remains poorly understood. In Escherichia coli, the TusDCB complex catalyzes 2-thiolation of wobble uridines in lysine-, glutamate-, and glutamine-decoding tRNAs. To investigate its role in intestinal virulence, we constructed an in-frame tusDCB deletion mutant in enterohemorrhagic Escherichia coli (EHEC). Comparative analyzes revealed that deletion of tusDCB reduced...

Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, can infect intact corneal epithelium, leading to inflammation, corneal perforation, and blindness. Models for studying this type of gonococcal infection are few and limited. We have tested stratified, polarized cornea models based on an immortalized hTCEpi corneal epithelium cell line for infection research using four derivatives of the N. gonorrhoeae MS11 strain that differ in pilus expression. We show...

Clostridioides difficile and vancomycin-resistant Enterococcus faecium (VRE) are commonly co-isolated from hospitalized patients. We sought to develop a co-culture biofilm model to characterize interactions between these two opportunistic pathogens. Upon growth in biofilm-promoting media containing added glucose, fructose, or trehalose, VRE produces sufficient acid to lower the pH and inhibit growth of C. difficile. We found this effect depended on the carbon source, and that acidification by...

As a zoonotic opportunistic pathogen, adhesion to the porcine upper respiratory tract epithelium is a prerequisite for Streptococcus suis serotype 2 (SS2) to breach epithelial barriers and cause systemic infections under certain conditions. In this study, we first demonstrated the adhesive function of the autolysin Atl of SS2 to swine tracheal epithelial cells. We found that Atl functions as a molecular bridge for epithelial adhesion. The Bsp-like domain (Atl^(Bsp)) specifically binds bacterial...