Adenosine A receptor as a potential regulator of survival mechanisms: new insights into leprosy neural damage.

Background: Leprosy is a chronic infectious disease caused by , which can lead to a disabling neurodegenerative condition. preferentially infects skin macrophages and Schwann cells-glial cells of the peripheral nervous system. The infection modifies the host cell lipid metabolism, subverting it in favor of the formation of cholesterol-rich lipid droplets (LD) that are essential for bacterial survival.

Baseline and end-of-treatment host serum biomarkers predict relapse in adults with pulmonary tuberculosis.

Background: There is a need for new tools for monitoring of the response to TB treatment. Such tools may allow for tailored treatment regimens, and stratify patients initiating TB treatment into different risk groups. We evaluated combinations between previously published host biomarkers and new candidates, as tools for monitoring TB treatment response, and prediction of relapse.

Drug resistant strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages.

, the causative agent of tuberculosis (TB), is considered one of the top infectious killers in the world. In recent decades, drug resistant (DR) strains of have emerged that make TB even more difficult to treat and pose a threat to public health. has a complex cell envelope that provides protection to the bacterium from chemotherapeutic agents.

Drug-resistant strains of : cell envelope profiles and interactions with the host.

In the past few decades, drug-resistant (DR) strains of (), the causative agent of tuberculosis (TB), have become increasingly prevalent and pose a threat to worldwide public health. These strains range from multi (MDR) to extensively (XDR) drug-resistant, making them very difficult to treat. Further, the current and future impact of the Coronavirus Disease 2019 (COVID-19) pandemic on the development of DR-TB is still unknown.

Immunological and metabolic characterization of environmental Mycobacterium chimaera infection in a murine model.

Mycobacterium chimaera causes pulmonary disease, but little is known of gradations in isolate virulence. Previously, 17 M. chimaera isolates were screened for survival in THP1 macrophages.

Polyunsaturated Fatty Acid-Derived Lipid Mediators as Potential Biomarkers for Leprosy Among Individuals with Asymptomatic Infection.

Intra-household contacts (HCs) of leprosy patients are at increased risk of infection by and about ∼5-10% will develop active disease. A prognostic tool to identify HCs with the greatest risk of progressing to active disease would enhance early leprosy diagnosis and optimize prophylactic intervention. Previous metabolomics studies suggest that host lipid mediators derived from ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are potential biomarkers for leprosy.

Localization of EccA at the growing pole in Mycobacterium smegmatis.

Background: Bacteria require specialized secretion systems for the export of molecules into the extracellular space to modify their environment and scavenge for nutrients. The ESX-3 secretion system is required by mycobacteria for iron homeostasis. The ESX-3 operon encodes for one cytoplasmic component (EccA) and five membrane components (EccB3 - EccE3 and MycP).

Biomarker selection and a prospective metabolite-based machine learning diagnostic for lyme disease.

We provide a pipeline for data preprocessing, biomarker selection, and classification of liquid chromatography-mass spectrometry (LCMS) serum samples to generate a prospective diagnostic test for Lyme disease. We utilize tools of machine learning (ML), e.g.

Corrigendum: Reductive Power Generated by Through Cholesterol Oxidation Contributes to Lipid and ATP Synthesis.

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Evaluation of autophagy mediators in myeloid-derived suppressor cells during human tuberculosis.

Myeloid-derived suppressor cells (MDSC) are induced during active TB disease to restore immune homeostasis but instead exacerbate disease outcome due to chronic inflammation. Autophagy, in conventional phagocytes, ensures successful clearance of M.tb.

Reductive Power Generated by Through Cholesterol Oxidation Contributes to Lipid and ATP Synthesis.

Upon infection, , an obligate intracellular bacillus, induces accumulation of cholesterol-enriched lipid droplets (LDs) in Schwann cells (SCs). LDs are promptly recruited to -containing phagosomes, and inhibition of this process decreases bacterial survival, suggesting that LD recruitment constitutes a mechanism by which host-derived lipids are delivered to intracellular . We previously demonstrated that has preserved only the capacity to oxidize cholesterol to cholestenone, the first step of the normal cholesterol catabolic pathway.

An -Like Operon and Its Relationship to Riboflavin Utilization and Mammalian Infectivity by Borrelia burgdorferi.

Riboflavin is an essential micronutrient, but its transport and utilization have remained largely understudied among pathogenic spirochetes. Here, we show that Borrelia burgdorferi, the zoonotic spirochete that causes Lyme disease, is able to import riboflavin via products of its -like operon as well as synthesize flavin mononucleotide and flavin adenine dinucleotide despite lacking canonical genes for their synthesis. Additionally, a mutant deficient in the -like operon is resistant to the antimicrobial effect of roseoflavin, a natural riboflavin analog, and is attenuated in a murine model of Lyme borreliosis.

Metabolic Response in Patients With Post-treatment Lyme Disease Symptoms/Syndrome.

Background: Post-treatment Lyme disease symptoms/syndrome (PTLDS) occurs in approximately 10% of patients with Lyme disease following antibiotic treatment. Biomarkers or specific clinical symptoms to identify patients with PTLDS do not currently exist and the PTLDS classification is based on the report of persistent, subjective symptoms for ≥6 months following antibiotic treatment for Lyme disease.

Methods: Untargeted liquid chromatography-mass spectrometry metabolomics was used to determine longitudinal metabolic responses and biosignatures in PTLDS and clinically cured non-PTLDS Lyme patients.

Dengue virus dominates lipid metabolism modulations in Wolbachia-coinfected Aedes aegypti.

Competition between viruses and Wolbachia for host lipids is a proposed mechanism of Wolbachia-mediated virus blocking in insects. Yet, the metabolomic interaction between virus and symbiont within the mosquito has not been clearly defined. We compare the lipid profiles of Aedes aegypti mosquitoes bearing mono- or dual-infections of the Wolbachia wMel strain and dengue virus serotype 3 (DENV3).

Quantitative 18F-FDG PET-CT scan characteristics correlate with tuberculosis treatment response.

Background: There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity.

Host Metabolic Response in Early Lyme Disease.

Lyme disease is a tick-borne bacterial illness that occurs in areas of North America, Europe, and Asia. Early infection typically presents as generalized symptoms with an erythema migrans (EM) skin lesion. Dissemination of the pathogen can result in multiple EM skin lesions or in extracutaneous manifestations such as Lyme neuroborreliosis.

Immunoproteomic analysis of Borrelia miyamotoi for the identification of serodiagnostic antigens.

The tick-borne spirochete, Borrelia miyamotoi, is an emerging pathogen of public health significance. Current B. miyamotoi serodiagnostic testing depends on reactivity against GlpQ which is not highly sensitive on acute phase serum samples.

Increased serum sialic acid is associated with morbidity and mortality in a murine model of dengue disease.

Dengue virus (DENV) causes the most prevalent arboviral infection of humans, resulting in a spectrum of outcomes, ranging from asymptomatic infection to dengue fever to severe dengue characterized by vascular leakage and shock. Previously, we determined that DENV nonstructural protein 1 (NS1) induces endothelial hyperpermeability, disrupts the endothelial glycocalyx layer (EGL) and triggers shedding of structural components, including sialic acid (Sia) and heparan sulfate. Here, using a murine model of dengue disease disease, we found high levels of Sia and NS1 circulating in mice with DENV-induced morbidity and lethal DENV infection.

Distinct serum biosignatures are associated with different tuberculosis treatment outcomes.

Biomarkers for TB treatment response and outcome are needed. This study characterize changes in immune profiles during TB treatment, define biosignatures associated with treatment outcomes, and explore the feasibility of predictive models for relapse. Seventy-two markers were measured by multiplex cytokine array in serum samples from 78 cured, 12 relapsed and 15 failed treatment patients from South Africa before and during therapy for pulmonary TB.

A pilot metabolomics study of tuberculosis immune reconstitution inflammatory syndrome.

Background: Diagnosis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is challenging and new tools are needed for early diagnosis as well as to understand the biochemical events that underlie the pathology in TB-IRIS.

Methods: Plasma samples were obtained from participants from a randomized HIV/TB treatment strategy study (AIDS Clinical Trials Group [ACTG] A5221) with (n = 26) and without TB-IRIS (n = 22) for an untargeted metabolomics pilot study by liquid-chromatography mass spectrometry. The metabolic profile of these participants was compared at the study entry and as close to the diagnosis of TB-IRIS as possible (TB-IRIS window).

Mycobacteria and their sweet proteins: An overview of protein glycosylation and lipoglycosylation in M. tuberculosis.

Post-translational modifications represent a key aspect of enzyme and protein regulation and function. Post-translational modifications are involved in signaling and response to stress, adaptation to changing environments, regulation of toxic and damaged proteins, proteins localization and host-pathogen interactions. Glycosylation in Mycobacterium tuberculosis (Mtb), is a post-translational modification often found in conjunction with acylation in mycobacterial proteins.