Small Interfering RNA Mediated Messenger RNA Knockdown in the Amphibian Pathogen Batrachochytrium dendrobatidis.

RNA interference (RNAi) has not been tested in the pandemic amphibian pathogen, Batrachochytrium dendrobatidis, but developing this technology could be useful to elucidate virulence mechanisms, identify therapeutic targets, and may present a novel antifungal treatment option for chytridiomycosis. To manipulate and decipher gene function, rationally designed small interfering RNA (siRNA) can initiate the destruction of homologous messenger RNA (mRNA), resulting in the "knockdown" of target gene expression. Here, we investigate whether siRNA can be used to manipulate gene expression in B.

Antibodies as clinical tools for tuberculosis.

Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Global research efforts to improve TB control are hindered by insufficient understanding of the role that antibodies play in protective immunity and pathogenesis. This impacts knowledge of rational and optimal vaccine design, appropriate diagnostic biomarkers, and development of therapeutics.

Glutathione is required for growth and cadmium tolerance in the amphibian chytrid fungus, Batrachochytrium dendrobatidis.

Batrachochytrium dendrobatidis (Bd) is a lethal amphibian pathogen, partly due to its ability to evade the immune system of susceptible frog species. In many pathogenic fungi, the antioxidant glutathione is a virulence factor that helps neutralise oxidative stressors generated from host immune cells, as well as other environmental stressors such as heavy metals. The role of glutathione in stress tolerance in Bd has not been investigated.

Effect of Savirin or Ticagrelor Treatment on the Expression of Commonly Used Reference Genes in .

Reference genes are frequently used for the normalization of quantitative reverse transcriptase PCR (qRTPCR) data in gene expression studies. is one of the most common causes of biofilm-related infections. Savirin and ticagrelor show in vitro as well as in vivo antibiofilm activity against .

Seroepidemiology of Strongyloides spp. Infection in Balimo, Western Province, Papua New Guinea.

Strongyloidiasis in Papua New Guinea (PNG) is poorly understood. There have been limited surveys describing the levels of endemicity in some regions of PNG, but in the Western Province, its occurrence and level of burden are unknown. This study aimed to determine the seroepidemiology of Strongyloides spp.

Effect of savirin in the prevention of biofilm-related prosthetic joint infection.

Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated . In a recent experimental study, savirin has been used to prevent and treat skin infections in animal models. We explored the application of savirin in a PJI mouse model to determine its utility as an adjunct therapy to prevent PJI.

The Effect of Tropical Temperatures on the Quality of RNA Extracted from Stabilized Whole-Blood Samples.

Whole-blood-derived transcriptional profiling is widely used in biomarker discovery, immunological research, and therapeutic development. Traditional molecular and high-throughput transcriptomic platforms, including molecular assays with quantitative PCR (qPCR) and RNA-sequencing (RNA-seq), are dependent upon high-quality and intact RNA. However, collecting high-quality RNA from field studies in remote tropical locations can be challenging due to resource restrictions and logistics of post-collection processing.

Non-Antimicrobial Adjuvant Therapy Using Ticagrelor Reduced Biofilm-Related Prosthetic Joint Infection.

Prosthetic joint infection (PJI), frequently caused by , leads to a significant arthroplasty failure rate. Biofilm is a crucial virulence factor of that is intrinsic to the pathogenesis of PJI. Biofilm-related infections are recalcitrant to antibiotic treatment.

Identification of defective early immune responses to Burkholderia pseudomallei infection in a diet-induced murine model of type 2 diabetes.

Co-occurrence of bacterial infections with type 2 diabetes (T2D) is a global problem. Melioidosis caused by Burkholderia pseudomallei is 10 times more likely to occur in patients with T2D, than in normoglycemic individuals. Using an experimental model of T2D, we observed that greater susceptibility in T2D was due to differences in proportions of infiltrating leucocytes and reduced levels of MCP-1, IFN-γ and IL-12 at sites of infection within 24 h post-infection.

Disparate Effects of Metformin on Mycobacterium tuberculosis Infection in Diabetic and Nondiabetic Mice.

Comorbid type 2 diabetes poses a great challenge to the global control of tuberculosis. Here, we assessed the efficacy of metformin (MET), an antidiabetic drug, in mice infected with a very low dose of In contrast to diabetic mice, infected nondiabetic mice that received the same therapeutic concentration of MET presented with significantly higher disease burden. This warrants further studies to investigate the disparate efficacy of MET against tuberculosis in diabetic and nondiabetic individuals.

Increased susceptibility to Mycobacterium tuberculosis infection in a diet-induced murine model of type 2 diabetes.

Tuberculosis (TB)-type 2 diabetes mellitus (T2D) comorbidity is re-emerging as a global public health problem. T2D is a major risk factor for increased susceptibility to TB infection and reactivation leading to higher morbidity and mortality. The pathophysiological mechanisms of T2D contributing to TB susceptibility are not fully understood, but likely involve dysregulated immune responses.

A systematic approach to simultaneously evaluate safety, immunogenicity, and efficacy of novel tuberculosis vaccination strategies.

Tuberculosis (TB) is the deadliest infectious disease worldwide. Bacille-Calmette-Guérin (BCG), the only licensed TB vaccine, affords variable protection against TB but remains the gold standard. BCG improvement is focused around three strategies: recombinant BCG strains, heterologous routes of administration, and booster vaccination.

Spatial distribution of tuberculosis in a rural region of Western Province, Papua New Guinea.

Introduction: There is a high burden of tuberculosis (TB) in the Western Province, Papua New Guinea. This study aims to describe the spatial distribution of TB in the Balimo District Hospital (BDH) catchment area to identify TB patient clusters and factors associated with high rates of TB.

Methods: Information about TB patients was obtained from the BDH TB patient register for the period 26 April 2013 to 25 February 2017.

Diversity of Mycobacterium tuberculosis in the Middle Fly District of Western Province, Papua New Guinea: microbead-based spoligotyping using DNA from Ziehl-Neelsen-stained microscopy preparations.

Tuberculosis remains the world's leading cause of death from an infectious agent, and is a serious health problem in Papua New Guinea (PNG) with an estimated 36,000 new cases each year. This study describes the genetic diversity of Mycobacterium tuberculosis among tuberculosis patients in the Balimo/Bamu region in the Middle Fly District of Western Province in PNG, and investigates rifampicin resistance-associated mutations. Archived Ziehl-Neelsen-stained sputum smears were used to conduct microbead-based spoligotyping and assess genotypic resistance.

Anti-streptococcal antibody and T-cell interactions with vascular endothelial cells initiate the development of rheumatic carditis.

The role of group A streptococcal and Streptococcus dysgalactiae subspecies equisimilis M-protein specific Abs and T-cells in endothelial cell activation was investigated using cultured rat aortic endothelial cells, and in a rat model of autoimmune valvulitis. Heat inactivated serum and mononuclear cells from streptococcal M-protein immunized rats independently induced upregulation of the endothelial cell adhesion molecules, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in cultured cells. We also observed T-cell migration across endothelial cell monolayers incubated with serum from M-protein-immunized rats.

Dysregulation of key cytokines may contribute to increased susceptibility of diabetic mice to Mycobacterium bovis BCG infection.

Diabetes is one of the major co-morbidities contributing to the high global burden of tuberculosis (TB). The increased susceptibility of individuals with type 2 diabetes (T2D) to TB is multifactorial and may influence the efficacy of vaccines. This study was undertaken to determine the early immune responses that occur following infection with Mycobacterium bovis Bacille Calmette-Guérin (BCG) in a diet-induced murine model of T2D.

Molecular Evidence of Drug-Resistant Tuberculosis in the Balimo Region of Papua New Guinea.

Papua New Guinea (PNG) has a high burden of tuberculosis (TB), including drug-resistant TB (DR-TB). DR-TB has been identified in patients in Western Province, although there has been limited study outside the provincial capital of Daru. This study focuses on the Balimo region of Western Province, aiming to identify the proportion of DR-TB, and characterise (MTB) drug resistance-associated gene mutations.

9- and 13-HODE regulate fatty acid binding protein-4 in human macrophages, but does not involve HODE/GPR132 axis in PPAR-γ regulation of FABP4.

Background: Both activation of monocytes and increased serum fatty acid binding protein-4 (FABP4) occur in diabetes and are associated with increased atherosclerosis. The oxidized lipid, 9-hydroxyoctadecadienoic acid (9-HODE) increases FABP4 in macrophages, and is a ligand for G protein-coupled receptor 132 (GPR132). We investigated the involvement of GPR132 in mediating the 9-, 13-HODE stimulation of FABP4 secretion, and whether GPR132 expression is increased in monocytes from patients with type 2 diabetes.

Group G Streptococcus Induces an Autoimmune Carditis Mediated by Interleukin 17A and Interferon γ in the Lewis Rat Model of Rheumatic Heart Disease.

Acute rheumatic fever and rheumatic heart disease (ARF/RHD) have long been described as autoimmune sequelae of Streptococcus pyogenes or group A streptococcal (GAS) infection. Both antibody and T-cell responses against immunodominant GAS virulence factors, including M protein, cross-react with host tissue proteins, triggering an inflammatory response leading to permanent heart damage. However, in some ARF/RHD-endemic regions, throat carriage of GAS is low.

Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B. mallei-like Variation in the bimA Motility Gene, Australia.

Neurologic melioidosis is a serious, potentially fatal form of Burkholderia pseudomallei infection. Recently, we reported that a subset of clinical isolates of B. pseudomallei from Australia have heightened virulence and potential for dissemination to the central nervous system.

Wnt Signaling Pathway Inhibitor Sclerostin Inhibits Angiotensin II-Induced Aortic Aneurysm and Atherosclerosis.

Objective: Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations.

Approach And Results: SOST protein was downregulated in human and mouse AA samples compared with controls.

Anti-mycobacterial function of macrophages is impaired in a diet induced model of type 2 diabetes.

Type 2 diabetes (T2D) is one of the major risk factors for tuberculosis (TB). In this study, a diet induced murine model of T2D (DIMT2D) was developed and characterized in the context of metabolic, biochemical and histopathological features following diet intervention. Mycobacterial susceptibility was investigated using Mycobacterium fortuitum as a surrogate.