Superoxide Dismutase: A Key Enzyme for the Survival of Intracellular Pathogens in Host

Superoxide dismutase (SOD) is a crucial enzyme required to maintain the redox potential of the cells. It plays a vital role in protecting normal cells from reactive oxygen species (ROS) produced during many intracellular pathogens infections. SOD removes excess superoxide radicals (O2−) by converting them to hydrogen peroxide (H2O2) and molecular oxygen (O2). Several superoxide dismutase enzymes have been identified based on the metal ion as a cofactor. Human SOD differs from the intracellular pathogens in having Cu/Zn and Mn as metal cofactors. However, SOD of intracellular pathogens such as Trypanosoma, Leishmania, Plasmodium, and Mycobacterium have iron (Fe) as metal cofactors. Iron Superoxide Dismutase (FeSOD) is an essential enzyme in these pathogens that neutralizes the free radical of oxygen (O−) and prevents the formation of Peroxynitrite anion (ONOO−), helping the pathogens escape from redox-based cytotoxic killing. Moreover, most intracellular bacteria hold MnSOD or FeSOD in their cytoplasm such as Salmonella and Staphylococcus, whereas periplasm of some pathogenic bacteria and fungi are also cofactors with Cu/Zn and identified as CuZnSOD. This chapter will review the various types SOD present in intracellular pathogens and their role in the survival of these pathogens inside their host niche

Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis

Visceral leishmaniasis (VL) is a life-threatening disease characterized by uncontrolled parasitization of the spleen, liver, and bone marrow. Interleukin (IL)-10 has been implicated in the suppression of host immunity in human VL based on the elevated levels of IL-10 observed in plasma and lesional tissue, and its role in preventing clearance of Leishmania donovani in murine models of VL. The aim of this study was to identify the cellular source of IL-10 in human VL and determine if CD4+CD25+ (Foxp3high) regulatory T (T reg) cells are associated with active disease. We analyzed surface marker and gene expression in peripheral blood mononuclear cells and splenic aspirates from Indian VL patients before and 3–4 wk after treatment with Amphotericin B. The results did not point to an important role for natural CD4+CD25+ (Foxp3high) T reg cells in human VL. They did not accumulate in and were not a major source of IL-10 in the spleen, and their removal did not rescue antigen-specific interferon γ responses. In contrast, splenic T cells depleted of CD25+ cells expressed the highest levels of IL-10 mRNA and were the predominant lymphocyte population in the VL spleen. The elevated levels of IL-10 in VL plasma significantly enhanced the growth of L. donovani amastigotes in human macrophages. The data implicate IL-10–producing CD25−Foxp3− T cells in the pathogenesis of human VL

Leptin Functions in Infectious Diseases

Leptin, a pleiotropic protein has long been recognized to play an important role in the regulation of energy homeostasis, metabolism, neuroendocrine function, and other physiological functions through its effects on the central nervous system (CNS) and peripheral tissues. Leptin is secreted by adipose tissue and encoded by the obese (ob) gene. Leptin acts as a central mediator which regulates immunity as well as nutrition. Importantly, leptin can modulate both innate and adaptive immune responses. Leptin deficiency/resistance is associated with dysregulation of cytokine production, increased susceptibility toward infectious diseases, autoimmune disorders, malnutrition and inflammatory responses. Malnutrition induces a state of immunodeficiency and an inclination to death from communicable diseases. Infectious diseases are the disease of poor who invariably suffer from malnutrition that could result from reduced serum leptin levels. Thus, leptin has been placed at the center of many interrelated functions in various pathogenic conditions, such as bacterial, viruses and parasitic infections. We review herein, the recent advances on the role of leptin in malnutrition in pathogenesis of infectious diseases with a particular emphasis on parasitic diseases such as Leishmaniasis, Trypanosomiasis, Amoebiasis, and Malaria

COVID-19 Severity in Obesity: Leptin and Inflammatory Cytokine Interplay in the Link Between High Morbidity and Mortality

Obesity is one of the foremost risk factors in coronavirus infection resulting in severe illness and mortality as the pandemic progresses. Obesity is a well-known predisposed chronic inflammatory condition. The dynamics of obesity and its impacts on immunity may change the disease severity of pneumonia, especially in acute respiratory distress syndrome, a primary cause of death from SARS-CoV-2 infection. The adipocytes of adipose tissue secret leptin in proportion to individuals’ body fat mass. An increase in circulating plasma leptin is a typical characteristic of obesity and correlates with a leptin-resistant state. Leptin is considered a pleiotropic molecule regulating appetite and immunity. In immunity, leptin functions as a cytokine and coordinates the host’s innate and adaptive responses by promoting the Th1 type of immune response. Leptin induced the proliferation and functions of antigen-presenting cells, monocytes, and T helper cells, subsequently influencing the pro-inflammatory cytokine secretion by these cells, such as TNF-α, IL-2, or IL-6. Leptin scarcity or resistance is linked with dysregulation of cytokine secretion leading to autoimmune disorders, inflammatory responses, and increased susceptibility towards infectious diseases. Therefore, leptin activity by leptin long-lasting super active antagonist’s dysregulation in patients with obesity might contribute to high mortality rates in these patients during SARS-CoV-2 infection. This review systematically discusses the interplay mechanism between leptin and inflammatory cytokines and their contribution to the fatal outcomes in COVID-19 patients with obesity

Evaluation of Blood Agar Microtiter Plates for Culturing Leishmania Parasites To Titrate Parasite Burden in Spleen and Peripheral Blood of Patients with Visceral Leishmaniasis▿

Serial dilution of blood and spleen biopsy specimens, plated on Novy-MacNeal-Nicolle (NNN) blood agar using microtiter culture plates, is a sensitive and reproducible method for detection and growth of Leishmania parasites. Plates could be easily monitored, and growth could be rapidly detected. Moreover, parasite number may be estimated using this technique

Impact of Potassium Inoculants and Biotite on Soil Microbial Population and Enzymatic Activity under Maize (Zea mays L.) Cultivation in Gangetic Plains

The study explores the impact of potassium inoculants and black mica on soil microbial populations and enzymatic activity in maize cultivated soils. Microbial communities fueled by root exudates play essential roles in nutrient cycling, plant health, and soil structure. This study investigates the effects of potassium-solubilizing bacteria (KSB) and mineral potassium on microbial populations and enzymatic activity across different growth stages of maize. The experiment was conducted in randomized block design with 14 treatments, including combinations of KSB isolates, mineral potassium, and inorganic potassium. Microbial populations (bacteria, fungi, actinomycetes, and KSB) were quantified using serial dilution and plating techniques. Enzymatic activities (dehydrogenase, phosphatase, and urease) were assessed to understand nutrient interactions and microbial influences. The findings indicate that all treatments exhibited increased microbial populations compared to the control. Notably, treatment 75% recommended potassium dose + 25% potassium from Biotite + OVPS 05 consistently demonstrated the highest microbial growth. The presence of KSB appeared crucial in enhancing bacterial and fungal populations. Additionally, enzymatic activities were significantly influenced by treatments, with 75% recommended potassium dose + 25% potassium from Biotite + OVPS 05 showing the highest dehydrogenase, alkaline phosphatase, and urease activities. These results suggest that the combination of KSB isolates and mineral potassium contributes to enhanced microbial populations and soil enzymatic activities, offering insights into sustainable agriculture practices that balance productivity and soil health. The study sheds light on the intricate relationships between microorganisms, nutrients, and soil biochemical processes, providing valuable guidance for future agricultural strategies

MOESM1 of Homology modelling, molecular docking, and molecular dynamics simulations reveal the inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase enzyme by Withaferin-A

Additional file 1: Figure S1. The structures of ligands: (A) Withaferin-A, (B) Methotrexate, (C) DHFA drawn using Chemdraw ultra version 12.0 software. Figure S2. Sequence identity between Hu DHFR and Ld DHFR-TS. Asterisks indicate identical amino acids. Dots and colons indicate conserved amino acid substitutions. Dashes indicate gaps. Figure S3. Sequence identity between Hu TS and Ld DHFR-TS. Asterisks indicate identical amino acids. Dots and colons indicate conserved amino acid substitutions. Dashes indicate gaps. Figure S4. Sequence identity between Ld DHFR-TS and T.cruzichain A. Asterisks indicate identical amino acids. Dots and colons indicate conserved amino acid substitutions. Dashes indicate gaps. Figure S5. Ramachandran Plot: (A) Modelled Ld DHFR-TS and (B) reference T. cruzi DHFR-TS obtained using PROCHECK. Figure S6. Local quality estimate of (A) modelled Ld DHFR-TS and (B) reference T.cruzi DHFR-TS obtained from Swiss model. Figure S7. Secondary structures of (A) modelled Ld DHFR-TS and (B) reference T.cruzi DHFR-TS obtained from PDB sum. Table S1. Features of the generated Ld DHFR-TS model from Swiss model. Table S2. Ramachandran plot Statistics from PROCHECK results for modelled Ld DHFR-TS protein and reference T. cruzi DHFR-TS protein. Table S3. Drug likeness properties of WA from molsoft

Rapid, Noninvasive Diagnosis of Visceral Leishmaniasis in India: Comparison of Two Immunochromatographic Strip Tests for Detection of Anti-K39 Antibody

Used with blood or serum, a new anti-K39 antibody immunochromatographic strip test (IT-Leish; DiaMed AG) proved sensitive (range, 99 to 100%) and specific (range, 95 to 100%) for the noninvasive serodiagnosis of visceral leishmaniasis in India. Used with serum, the IT-Leish test and the existing Kalazar Detect test (InBios International, Inc.) yielded comparable results for symptomatic infection and identified apparent subclinical infection in 15 to 32% of healthy residents in a region where visceral leishmaniasis is highly endemic