Infection and Immunity

Diabetic wounds are often infected with microbes, which perpetuate inflammation, and stall wound healing. The bacterium Group B Streptococcus (GBS) is frequently isolated from diabetic wounds; however, little is known about how GBS adapts to survive in this niche. Previously, we found that GBS acquires stable mutations in the major two-component system CovRS during murine diabetic wound infection that result in increased pigmentation. Here, we further characterize these pigmented variants and...

Giardia duodenalis is an intestinal protozoan transmitted through contaminated food and water and is a major cause of diarrheal disease worldwide and has been linked to post-infectious sequelae and growth impairment in children. Quantifying parasite burden in vivo is essential for studying infection dynamics and host responses, yet commonly used methods (stool PCR, antigen detection, and terminal trophozoite counts from segments of the intestine) are limited by intermittent stool shedding,...

Pseudomonas aeruginosa is a high-priority pathogen and significant burden to health care worldwide. Although often regarded as an extracellular pathogen, P. aeruginosa is also capable of existing intracellularly in multiple cell types, including epithelial cells, goblet cells, and macrophages. This designation is attributed to two of its type three secretion system (T3SS)-dependent exotoxins, ExoS and ExoT, which inactivate host proteins that facilitate phagocytosis. However, studies...

Many intracellular pathogens stimulate host cell stress by directly or indirectly causing an imbalance in host nutrients. Depletion of amino acid pools, in particular, can act as a danger signal to infected cells. Using a restrictive host model of Salmonella enterica serovar Typhi (S. Typhi) infection, we identify early induction of the integrated stress response (ISR) by viable bacteria, but not by heat-killed bacteria. Genetic deletion of the amino acid-sensing ISR kinase GCN2 (also known as...

Bacterial physiology plays an important role in virulence. Being a pathogen is energetically expensive, requiring the production of specialized virulence factors and other proteins that enable survival within the host. The most efficient way for bacteria to generate the energy required for virulence is by electron-coupled oxidative phosphorylation, with oxygen as the terminal acceptor, also called aerobic respiration. Cytochrome oxidases are critical components of the electron transport chain...

Zoonotic infections constitute a major cause of reproductive failure and perinatal mortality in humans and animals. Among the most relevant etiological agents are Listeria monocytogenes, Brucella spp., and Toxoplasma gondii, which, despite distinct biological properties, share the capacity to breach placental defenses, establish intracellular niches, and impair fetal development. This review aims to synthesize current knowledge on the pathological and pathogenic mechanisms underlying fetal and...

Pulmonary infections caused by Mycobacterium abscessus (Mab), a rapidly growing nontuberculous mycobacterium (NTM), are rising in patients with preexisting lung disease. Unfortunately, the natural recalcitrance of Mab to antibiotics drives high rates of treatment failures. Understanding the initial host-pathogen interactions that result in Mab control or disease is critical to identify new therapeutic targets. Lung macrophages are the first immune cells that Mab encounters, yet how distinct...

The vaginal microbiome plays a critical role in reproductive health and undergoes characteristic remodeling during pregnancy that influences maternal and neonatal outcomes. Although the non-pregnant vaginal microbiome shows substantial inter-individual variability, pregnancy is associated with reduced microbial diversity and increased dominance by Lactobacillus species, creating a protective environment for fetal development. Disruption of this balance, termed vaginal dysbiosis, has been linked...

Chlamydia trachomatis (Ct) is a causal agent of upper reproductive tract pathology. There is a broad spectrum of cervical Ct load in infected women, and upper tract infection is associated with higher cervical Ct load. Recent studies indicate that bacterial vaginosis (BV) can modulate host-Ct outcomes. To identify features associated with BV status and Ct load, we performed an integrated multi-omics analysis of the cervicovaginal microbiome, tryptophan metabolome, and cytokines. Samples were...

Mycoplasma gallisepticum (MG) is an avian respiratory pathogen of global concern, responsible for hundreds of millions of dollars in estimated economic damage each year. Given that MG is distributed across every continent except Antarctica, any globally applicable vaccine must provide protection against numerous strains. We previously published that an R(low)-based subunit vaccine reduced both MG bacterial burden and tracheal pathology in a homologous infection model using virulent MG strain...

Hereditary hemochromatosis (HH) increases susceptibility to bacterial infections. In our previous study, an oral Yersinia pseudotuberculosis Δfur mutant (Δfur) infection led to intestinal barrier disruption and acute mortality in HH (Hfe^(-/-)) mice. However, the systemic features of this fulminant infection are incompletely characterized. Here, HH mice infected with a hyperyersiniabactin-producing Δfur rapidly develop sepsis symptoms, marked by an influx of immature CD101^(-) neutrophils with...

The Helicobacter pylori Cag Type IV Secretion System (T4SS) and the secreted CagA effector protein have key roles in gastric cancer pathogenesis. The Cag T4SS outer membrane core complex (OMCC) consists of an outer membrane cap (OMC), a periplasmic ring (PR), and a stalk. CagX and CagY span both the OMC (14 copies) and PR (17 copies) subassemblies of the OMCC. CagX is structurally related to VirB9 proteins found in other bacterial T4SSs, except for a unique 130-amino-acid region, designated as...

Neisseria gonorrhoeae (Gc) causes the sexually transmitted infection gonorrhea, an urgent public health concern. Gc infection elicits a robust neutrophil response and serum leakage, but Gc has developed specialized defenses to evade both complement and neutrophils. We recently reported that the classical complement pathway inhibitor C4b-binding protein (C4BP) binds to Gc and reduces phagocytic killing by neutrophils in a complement-independent manner. Here, we used a Chinese hamster ovary (CHO)...

To inhabit aerobic environments, microbes must be able to cope with the reactive byproducts of aerobic growth. These toxic compounds, also named reactive oxygen species (ROS), damage a variety of cellular macromolecules, and thus demand universal adaptive responses in microorganisms. Beyond ROS, microbes must also contend with exogenous oxidants such as reactive chlorine species (RCS) and reactive nitrogen species (RNS). In the context of antimicrobial activity, discussions on exogenous reactive...

Staphylococcus aureus (S. aureus) is a highly virulent pathogen responsible for chronic infections such as osteomyelitis. Although its interaction with the host immune system has been widely studied, the specific role of inflammasomes in regulating the infection within macrophages remains unclear. We investigated this question using bone marrow-derived macrophages (BMDMs) infected with S. aureus for up to 96 hours (h). We observed a significant reduction in intracellular bacterial load beginning...