Interplay of human macrophage response and natural resistance of ( .) to pentavalent antimony.

Unlabelled: Macrophages are the principal host cells of . in human infection and play a critical role in controlling infection and enabling parasite survival and persistence. Nevertheless, understanding of drug resistance in leishmaniasis has primarily focused on the parasite.

da_Tracker: Automated workflow for high throughput single cell and single phagosome tracking in infected cells.

Time-lapse microscopy has emerged as a crucial tool in cell biology, facilitating a deeper understanding of dynamic cellular processes. While existing tracking tools have proven effective in detecting and monitoring objects over time, the quantification of signals within these tracked objects often faces implementation constraints. In the context of infectious diseases, the quantification of signals at localized compartments within the cell and around intracellular pathogens can provide even deeper insight into the interactions between the pathogen and host cell organelles.

Innate biosignature of treatment failure in human cutaneous leishmaniasis.

The quality and magnitude of the immune and inflammatory responses determine the clinical outcome of infection, and contribute to the efficacy of antileishmanial treatments. However, the precise immune mechanisms involved in healing or in chronic immunopathology of human cutaneous leishmaniasis (CL) are not completely understood. Through sequential transcriptomic profiling of blood monocytes (Mo), neutrophils (Nφ), and eosinophils (Eφ) over the course of systemic treatment with meglumine antimoniate, we discovered that a heightened and sustained Type I interferon (IFN) response signature is a hallmark of treatment failure (TF) in CL patients.

The stand-alone regulator RofA exhibits characteristics of a PRD-containing virulence regulator.

[group A streptococcus (GAS)] is a human pathogen capable of infecting diverse tissues. To successfully infect these sites, GAS must detect available nutrients and adapt accordingly. The phosphoenolpyruvate transferase system (PTS) mediates carbohydrate uptake and metabolic gene regulation to adapt to the nutritional environment.

da_Tracker: Automated workflow for high throughput single cell and single phagosome tracking in infected cells.

Time-lapse microscopy has emerged as a crucial tool in cell biology, facilitating a deeper understanding of dynamic cellular processes. While existing tracking tools have proven effective in detecting and monitoring objects over time, the quantification of signals within these tracked objects often faces implementation constraints. In the context of infectious diseases, the quantification of signals at localized compartments within the cell and around intracellular pathogens can provide even deeper insight into the interactions between the pathogen and host cell organelles.

Macrophage metallothioneins participate in the antileishmanial activity of antimonials.

Host cell functions that participate in the pharmacokinetics and pharmacodynamics (PK/PD) of drugs against intracellular pathogen infections are critical for drug efficacy. In this study, we investigated whether macrophage mechanisms of xenobiotic detoxification contribute to the elimination of intracellular upon exposure to pentavalent antimonials (Sb). Primary macrophages from patients with cutaneous leishmaniasis (CL) (n=6) were exposed to infection and Sb, and transcriptomes were generated.

Consolidation of a Molecular Signature of Healing in Cutaneous Leishmaniasis Is Achieved during the First 10 Days of Treatment.

The immune response is central to the pathogenesis of cutaneous leishmaniasis (CL). However, most of our current understanding of the immune response in human CL derives from the analysis of systemic responses, which only partially reflect what occurs in the skin. In this study, we characterized the transcriptional dynamics of skin lesions during the course of treatment of CL patients and identified gene signatures and pathways associated with healing and nonhealing responses.

Characterization of the Entner-Doudoroff pathway in catheter-associated urinary tract infections.

is an opportunistic nosocomial pathogen responsible for a subset of catheter-associated urinary tract infections (CAUTI). In a murine model of CAUTI, we previously demonstrated that urea within urine suppresses quorum sensing and induces the Entner-Doudoroff (E-D) pathway. The E-D pathway consists of the genes , , , and .

Characterization of the Entner-Douderoff Pathway in Catheter-associated Urinary Tract Infections.

is an opportunistic nosocomial pathogen responsible for catheter-associated urinary tract infections (CAUTI). In a murine model of CAUTI, we previously demonstrated that urea within urine suppresses quorum sensing and induces the Entner-Douderoff (E-D) pathway. The E-D pathway consists of the genes , , , and .

Catheter-associated urinary tract infection by progresses through acute and chronic phases of infection.

Healthcare-associated infections are major causes of complications that lead to extended hospital stays and significant medical costs. The use of medical devices, including catheters, increases the risk of bacterial colonization and infection through the presence of a foreign surface. Two outcomes are observed for catheterized patients: catheter-associated asymptomatic bacteriuria and catheter-associated urinary tract infection (CAUTI).

Loss of Encoding the δ-Factor of RNA Polymerase Impacts Pathophysiology of the M1T1 Strain 5448.

Streptococcus pyogenes, also known as the Group A Streptococcus (GAS), is a Gram-positive bacterial pathogen of major clinical significance. Despite remaining relatively susceptible to conventional antimicrobial therapeutics, GAS still causes millions of infections and hundreds of thousands of deaths each year worldwide. Thus, a need for prophylactic and therapeutic interventions for GAS is in great demand.

Physiological magnesium concentrations increase fidelity of diverse reverse transcriptases from HIV-1, HIV-2, and foamy virus, but not MuLV or AMV.

Reverse transcriptases (RTs) are typically assayed using optimized Mg concentrations (~5-10 mM) several-fold higher than physiological cellular free Mg (~0.5 mM). Recent analyses demonstrated that HIV-1, but not Moloney murine leukaemia (MuLV) or avain myeloblastosis (AMV) virus RTs has higher fidelity in low Mg.

Early Leukocyte Responses in Models of Healing and Non-Healing Human Infections.

Early host-pathogen interactions drive the host response and shape the outcome of natural infections caused by intracellular microorganisms. These interactions involve a number of immune and non-immune cells and tissues, along with an assortment of host and pathogen-derived molecules. Our current knowledge has been predominantly derived from research on the relationships between the pathogens and the invaded host cell(s), limiting our understanding of how microbes elicit and modulate immunological responses at the organismal level.

PIWI silencing mechanism involving the retrotransposon nimbus orchestrates resistance to infection with Schistosoma mansoni in the snail vector, Biomphalaria glabrata.

Background: Schistosomiasis remains widespread in many regions despite efforts at its elimination. By examining changes in the transcriptome at the host-pathogen interface in the snail Biomphalaria glabrata and the blood fluke Schistosoma mansoni, we previously demonstrated that an early stress response in juvenile snails, manifested by induction of heat shock protein 70 (Hsp 70) and Hsp 90 and of the reverse transcriptase (RT) domain of the B. glabrata non-LTR- retrotransposon, nimbus, were critical for B.

A zinc finger protein that is implicated in the control of epimastigote-specific gene expression and metacyclogenesis.

Trypanosoma cruzi has three biochemically and morphologically distinct developmental stages that are programmed to rapidly respond to environmental changes the parasite faces during its life cycle. Unlike other eukaryotes, Trypanosomatid genomes contain protein coding genes that are transcribed into polycistronic pre-mRNAs and have their expression controlled by post-transcriptional mechanisms. Transcriptome analyses comparing three stages of the T.

Draft Genome Sequence of Pseudomonas aeruginosa Strain PA14-UM.

is a Gram-negative nosocomial pathogen that is a leading cause of morbidity and mortality in cystic fibrosis patients and immunocompromised individuals worldwide. The isolate examined in this study, PA14-UM, is a well-characterized isolate utilized in studies from the University of Maryland.

Identification of Zinc-Dependent Mechanisms Used by Group B To Overcome Calprotectin-Mediated Stress.

Nutritional immunity is an elegant host mechanism used to starve invading pathogens of necessary nutrient metals. Calprotectin, a metal-binding protein, is produced abundantly by neutrophils and is found in high concentrations within inflammatory sites during infection. Group B (GBS) colonizes the gastrointestinal and female reproductive tracts and is commonly associated with severe invasive infections in newborns such as pneumonia, sepsis, and meningitis.

The transition of M-CSF-derived human macrophages to a growth-promoting phenotype.

Stimulated macrophages are potent producers of inflammatory mediators. This activity is highly regulated, in part, by resolving molecules to prevent tissue damage. In this study, we demonstrate that inflammation induced by Toll-like receptor stimulation is followed by the upregulation of receptors for adenosine (Ado) and prostaglandin E2 (PGE2), which help terminate macrophage activation and initiate tissue remodeling and angiogenesis.

Gene expression network analyses during infection with virulent and avirulent Trypanosoma cruzi strains unveil a role for fibroblasts in neutrophil recruitment and activation.

Chagas disease is caused by Trypanosoma cruzi, a protozoan parasite that has a heterogeneous population composed of a pool of strains with distinct characteristics, including variable levels of virulence. In previous work, transcriptome analyses of parasite genes after infection of human foreskin fibroblasts (HFF) with virulent (CL Brener) and non-virulent (CL-14) clones derived from the CL strain, revealed a reduced expression of genes encoding parasite surface proteins in CL-14 compared to CL Brener during the final steps of the intracellular differentiation from amastigotes to trypomastigotes. Here we analyzed changes in the expression of host genes during in vitro infection of HFF cells with the CL Brener and CL-14 strains by analyzing total RNA extracted from cells at 60 and 96 hours post-infection (hpi) with each strain, as well as from uninfected cells.

Immune Complex-Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity.

To maintain homeostasis, macrophages must be capable of assuming either an inflammatory or an anti-inflammatory phenotype. To better understand the latter, we stimulated human macrophages in vitro with TLR ligands in the presence of high-density immune complexes (IC). This combination of stimuli resulted in a broad suppression of inflammatory mediators and an upregulation of molecules involved in tissue remodeling and angiogenesis.

Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides.

Cell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. Here we identify gacH, a gene in the Streptococcus pyogenes group A carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA-secreted phospholipase A. Subsequent structural and phylogenetic analysis of the GacH extracellular domain revealed that GacH represents an alternative class of glycerol phosphate transferase.

Host and parasite responses in human diffuse cutaneous leishmaniasis caused by L. amazonensis.

Diffuse cutaneous leishmaniasis (DCL) is a rare form of leishmaniasis where parasites grow uncontrolled in diffuse lesions across the skin. Meta-transcriptomic analysis of biopsies from DCL patients infected with Leishmania amazonensis demonstrated an infiltration of atypical B cells producing a surprising preponderance of the IgG4 isotype. DCL lesions contained minimal CD8+ T cell transcripts and no evidence of persistent TH2 responses.

Inhibits Autocrine Type I IFN Signaling to Increase Intracellular Survival.

The type I IFNs (IFN-α and -β) are important for host defense against viral infections. In contrast, their role in defense against nonviral pathogens is more ambiguous. In this article, we report that IFN-β signaling in murine bone marrow-derived macrophages has a cell-intrinsic protective capacity against via the increased production of NO.

Glucose Levels Alter the Mga Virulence Regulon in the Group A Streptococcus.

Many bacterial pathogens coordinately regulate genes encoding important metabolic pathways during disease progression, including the phosphoenolpyruvate (PEP)-phosphotransferase system (PTS) for uptake of carbohydrates. The Gram-positive Group A Streptococcus (GAS) is a pathogen that infects multiple tissues in the human host. The virulence regulator Mga in GAS can be phosphorylated by the PTS, affecting Mga activity based on carbohydrate availability.