Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied

Background Macrophages play an important role in the host immune response against mycobacterial infection, and this process is regulated by various factors, including circular RNAs (circRNAs). We intended to explore the role of circ_0001490 in tuberculosis (TB) using Mycobacterium tuberculosis (M.tb)-infected THP-1 macrophages. Methods Real-time quantitative polymerase chain reaction (RT-qPCR) and

Helminth induced expansion of regulatory T cells (Tregs) may take part in suppressing protective host responses during tuberculosis (TB), although Tregs functionality and link to TB disease severity remains unexplored. We investigated the species-specific effect of helminths on frequency and TGF-β producing capacity of Tregs, and possible connection to TB disease severity. 89 pulmonary TB patients

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a major cause of death worldwide. Diverse genotypes have been demonstrated to drive the epidemiology of drug resistant (DR-) TB globally. Currently, there is limited knowledge on the genotypes and transmission dynamics of M. tuberculosis in Zambia. This study aimed to describe the genotypes of DR-TB from the Copperbelt and Northern regions

Much of the morbidity and mortality caused by tuberculous meningitis (TBM) is mediated by a dysregulated immune response. Effective host-directed therapy is therefore critical to improve survival and clinical outcomes. Currently only one host-directed therapy (HDT), corticosteroids, is proven to improve mortality. However, there is no evidence that corticosteroids reduce morbidity and the mechanism

The purpose of the present study was to evaluate a real-time PCR system for 12 nontuberculous mycobacteria (NTM) species identification developed by Central Tuberculosis Research Institute (CTRI; Moscow, Russia) in cooperation with Syntol LLC (Moscow, Russia). NTM cultures (210 strains, 19 species), Mycobacterium tuberculosis complex (MTBC) cultures (21 strains, 2 species), non-mycobacterial microorganisms

The purpose of this study was to investigate the minimum level of heteroresistance that predicts poor tuberculosis treatment outcomes. This retrospective study enrolled 45 new tuberculosis patients with varied treatment outcomes and 16 drug-susceptible retreatment cases. Pretreatment isolates from these 61 patients were whole genome sequenced to detect heteroresistance. Heteroresistance was not found

Because of the current limits of immunological tests in the diagnosis of tuberculosis there is a need to identify new and rapid tests that can be carried out on a large scale in endemic countries and useful in the identification of infected subjects, but also able to discriminate those with latent infection from subjects with active. We have taken into consideration and analysed the LIODetect®TB-ST

Background There is an urgent need for new, accurate, rapid, and affordable tuberculosis (TB) diagnostic tests. The aim of the present study was to use mass spectrometry to identify new preliminary candidate TB diagnostic protein biomarkers in saliva obtained from individuals with TB, and patients with other respiratory diseases (ORD). Methods Saliva samples were collected from 22 individuals who self-presented

Tuberculous lymphadenitis (TBL) is defined by reduced proinflammatory cytokines and elevated CD4+, CD8+ T cells and decreased CD8+ cytotoxic markers. However, ex-vivo phenotyping of diverse leucocytes in TBL has not been done. We show activated and atypical B cells, myeloid dendritic cells (mDCs), classical, non-classical and intermediate monocytes, T regulatory (T regs) cells, CD4+ T cell effector

Tuberculosis remains one of the most significant causes of mortality worldwide and the current situation shows a re-emergence of TB due to the emergence of new antibiotic-resistant strains and the widespread of disease caused by immunodeficiencies. For these reasons, a big effort is made to improve the therapeutic strategies against Mycobacterium tuberculosis and to perform new therapeutic and diagnostic

Tumor necrosis factor (TNF) is essential for the host defense against tuberculosis (TB). However, scarcity or excessive TNF production in macrophages can also increase susceptibility to TB. The precise mechanisms underlying how Mycobacterium tuberculosis (Mtb) induces TNF over-expression are unclear. Here, we show that Mtb infection significantly increases 5-hydroxylmethylocytosine (5hmC) levels in

Objectives 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography- Computed Tomography (PET/CT) scans can be used to assess healing following treatment for spinal tuberculosis (TB) but have limited accessibility and high cost. This study investigated the association between immune biomarkers and FDG-PET/CT activity after ≥9 months of treatment for spinal TB. Methods Patients who had completed ≥9

Whole genome sequencing (WGS) analysis in tuberculosis allows the prediction of drug-resistant phenotypes, identification of lineages, and to better understanding of the epidemiology and transmission chains. Nevertheless the procedure has been scarcely assessed in Mexico, in this work we analyze by WGS isolates of Mycobacterium tuberculosis circulating in Jalisco, Mexico. Lineage and phylogenetic characterization

Mycobacterium bovis BCG has been the only practical vaccine for tuberculosis. However, BCG cannot fully prevent adult pulmonary tuberculosis. Therefore, the improvement of BCG vaccine is necessary. We previously produced recombinant (r) BCG (BCG-PEST) for the better control of tuberculosis. BCG-PEST was developed by introducing PEST-Heat Shock Protein (HSP)70-Major Membrane Protein (MMP)–II–PEST fusion

While some healthcare systems have shifted to molecular diagnostics, culture still remains the gold standard for tuberculosis diagnosis, but it is limited by its long duration to a positive result. Methods to reduce time to culture positivity (TTP) are urgently required. We determined if growth factor supplementation in the mycobacterial growth indicator tube (MGIT) culture system reduces TTP. MGITs

It is important to accurately quantify Mycobacterium tuberculosis (Mtb) load in laboratory-based tuberculosis (TB) research. This study aims to determine if real-time quantitative PCR (qPCR) and digital PCR (dPCR) can be used instead of colony forming unit (CFU) enumeration, to quantify Mtb load in rhesus and cynomolgus macaque tissue samples. Tissue samples of actively infected high Mtb-burden rhesus

Objectives To determine the usefulness of hsa-miR-346, a potential biomarker enhancing the activity of non-tuberculous mycobacterial diseases, as a biomarker of tuberculosis activity. Methods We investigated whether hsa-miR-346 is secreted by human macrophages infected with Mycobacterium tuberculosis (M. tuberculosis) in an in vitro study. In addition, a cross-sectional study was conducted first to

Isoniazid (INH) remains a cornerstone for treatment of drug susceptible tuberculosis (TB), yet the quantitative structure-activity relationships for INH are not well documented in the literature. In this paper, we have evaluated a systematic series of INH analogs against contemporary Mycobacterium tuberculosis strains from different lineages and a few non-tuberculous mycobacteria (NTM). Deletion of

Multi-Drug-Resistant strains of Mycobacterium tuberculosis (MDR-TB) are a serious obstacle to global TB eradication. While most MDR-TB strains are infrequently transmitted, a few cause large transmission clusters that contribute substantially to local MDR-TB burdens. Here we examine whether the known mutations in these strains can explain their success. Drug resistance mutations differ in fitness costs

For tuberculosis to be eradicated, the transmission of Multi-Drug-Resistant and eXtensively Drug Resistant strains of Mycobacterium tuberculosis (MDR and XDR-TB) must be considerably reduced. Drug resistant strains were initially thought to have reduced fitness, and the majority of resistant strains may actually have compromised fitness because they are found in only one or a few patients. In contrast

Tuberculosis is initiated by the entry of Mycobacterium tuberculosis (Mtb) into macrophages in the lungs. A study of the cellular factors responsible for the entry of Mtb into host cells will potentially benefit the development of therapeutic treatments or preventive agents against Mtb infection. Using human THP1-derived macrophages as a model, we found that infection of Mtb H37Ra transiently reduced

Background Mycobacterium tuberculosis (MTB) sRNAs are abundant. However, the level of MTB sRNA in peripheral blood remains elusive. Methods Twenty MTB sRNAs annotated in the reference genome of H37Rv were detected in the plasma of 170 active pulmonary tuberculosis patients and 124 healthy people by qRT-PCR detection system. The differential expression of sRNAs were analyzed in two groups. The value

There is a clear need to improve host-directed therapy for tuberculous meningitis (TBM), the most severe and deadly manifestation of tuberculosis. Corticosteroids represent the only host-directed therapy of proven benefit in TBM, yet their effect is modest, the mechanism by which they reduce mortality is unknown, and there is evidence for heterogeneity in their effect. Novel therapeutic approaches

Background The remains of a 3-5 year-old child from the late mediaeval cemetery serving the Priory of St. Peter and St. Paul, Taunton, Somerset, UK was the subject of an aDNA study. Objective The aim was to distinguish between two differential diagnoses suggested by earlier osteological examination of the remains; either tuberculosis or Langerhans cell histiocytosis. Findings The remains tested positive

Mycobacterium tuberculosis is the major etiological agent for tuberculosis (TB), which is the leading cause of single pathogen infection-related deaths worldwide. The End TB Strategy of the World Health Organization aimed to decrease the incidence of TB by 20% between 2015 and 2020, which was not achieved. Here, the growth-inhibitory effects of tris-(1,10-phenanthroline) iron (II) complex ([Fe(phen)3]2+)

Antimalarial drugs have been suggested as promising scaffolds with anti-tubercular activities. In this work, we demonstrated, for the first time, the effectiveness of tafenoquine against mycobacteria. Firstly, tafenoquine inhibited the growth of Mycobacterium smegmatis and Mycobacterium tuberculosis with lower MICs values as compared to other antimalarial drugs, such as mefloquine, chloroquine, and

Tuberculosis (TB) is an infectious disease that poses a serious threat to human health. Rifampin (RIF) is an important first-line anti-TB drug, and rifampin resistance (RIF-R) is a key factor in formulating treatment regimen and evaluating the prognosis of TB. Compared with other drugs resistance, the RIF-R mechanism of Mycobacterium tuberculosis (M. tuberculosis) is one of the clearest, which is mainly

New tools to monitor treatment response and predict outcome from tuberculous meningitis (TBM) are urgently required. We retrospectively evaluated the 16S rRNA-based molecular bacterial load assay (MBLA) to quantify viable Mycobacterium tuberculosis in serial cerebrospinal fluid (CSF) from adults with TBM. 187 CSF samples were collected before and during the first two months of treatment from 99 adults

We investigated the preclinical efficacy and safety/tolerability of biodegradable polymeric particles containing isoniazid (INH) and rifabutin (RFB) dry powder for inhalation (DPI) as an adjunct to oral first-line therapy. Mice and guinea pigs infected with Mycobacterium tuberculosis H37Rv (Mtb) were treated with ∼80 and ∼300 μg of the DPI, respectively, for 3–4 weeks starting 3, 10, and 30 days post-infection

Host markers to monitor the response to tuberculosis (TB) therapy hold some promise. We evaluated the changes in concentration of Mycobacterium tuberculosis (M.tb)-induced soluble biomarkers during early treatment for predicting short- and long-term treatment outcomes. Whole blood samples from 30 cured and 12 relapsed TB patients from diagnosis, week 1, 2, and 4 of treatment were cultured in the presence

Several studies have documented the interaction between the immune and endocrine systems as an effective defense strategy against tuberculosis, involving the production of several molecules and immunological processes. In this study, we determined the effect of cortisol and dehydroepiandrosterone (DHEA) on the production of antimicrobial peptides such as cathelicidin and human β-defensin (HBD) −2,

Mycobacterium tuberculosis (MTB) has co-evolved with humans for decades and developed several mechanisms to evade host immunity. It can efficiently alter the host epigenome, thus playing a major role in immunomodulation by either activating or suppressing genes responsible for mounting an immune response against the pathogen. Epigenetic modifications such as DNA methylation and chromatin remodelling

Mycobacterium tuberculosis H37Ra (Mtb-Ra) ORF MRA_1916 is annotated as a D-amino acid oxidase (DAO). These enzymes perform conversion of d-amino acids to corresponding imino acids followed by conversion into α-keto-acids. In the present study Mtb-Ra recombinants with DAO knockout (KO) and knockout complemented with DAO over-expressing plasmid (KOC) were constructed. The growth studies showed loss of

The biomarker significance of IL-35, chemokines (CXCL9 and CXCL10) and human beta-defensins (hBD2 and hBD3) was determined in pulmonary tuberculosis (TB) of 105 Iraqi patients; 37 had active disease, 41 had multi-drug resistant (MDR) PTB and 27 had a relapse of TB. A control sample of 79 healthy persons was also included. Serum levels of markers were assessed using enzyme-linked immunosorbent assay

Tuberculosis is a major threat to global health and its increased incidence in adolescents as well as onset in the elderly presents a serious problem. One strategy to control tuberculosis involves taking advantage of Bacillus Calmette–Guérin's (BCG) superior effects on childhood tuberculosis. Accordingly, here we aimed to develop a booster vaccine for adults who received the BCG vaccine during early

Xinjiang is a unique region of Central Asian part of China. It is widely noted for high tuberculosis burden and particularly for growing prevalence of drug resistance. Understanding genotypic distribution of Mycobacterium tuberculosis could help clarify unknown causes for the spread of drug-resistant strains. We analyzed 986 M. tuberculosis isolates collected from Xinjiang. Two genotyping schemes,

Background Tuberculosis, one of the deadliest infectious diseases worldwide, is difficult to diagnose. As long noncoding RNAs (lncRNAs) were demonstrated to be promising biomarkers, we aimed to identify lncRNAs in plasma as potential biomarkers for tuberculosis. Methods We analyzed a GEO dataset (GSE94907) to identify the differential lncRNAs in serum exosomes between active tuberculosis (ATB) patients

Serine/threonine-protein kinases in Mycobacterium tuberculosis (Mtb) form a preeminent regulatory system required to establish and maintain the infection in the host. Herein, we sought to decipher the biological role of PknL with the help of a gene replacement mutant RvΔpknL. Deletion of pknL results in the compromised growth under redox stress. The mutant showed significant survival defects in peritoneal

BACKGROUND Timely drug resistance detection is essential to global tuberculosis management. Unfortunately, rapid molecular tests assess resistance to only a few drugs, with culture required for comprehensive susceptibility test results. METHODS We evaluated targeted next generation sequencing (tNGS) for tuberculosis on 40 uncultured sputum samples. Resistance profiles from tNGS were compared with profiles

Recently, the number of artificial intelligence powered computer-aided detection (CAD) products that detect tuberculosis (TB)-related abnormalities from chest X-rays (CXR) available on the market has increased. Although CXR is a relatively effective and inexpensive method for TB screening and triaging, a shortage of skilled radiologists in many high TB-burden countries limits its use. CAD technology

HIV infection is a major risk factor predisposing for Mycobacterium tuberculosis infection and progression to active tuberculosis (TB). As host immune response defines the course of infection, we aimed to identify immuno-endocrine changes over six-months of anti-TB chemotherapy in HIV+ people. Plasma levels of cortisol, DHEA and DHEA-S, percentages of CD4+ regulatory T cell subsets and number of IFN-γ-secreting

Abstract We hypothesised that individuals with immunological sensitisation to Mycobacterium tuberculosis (Mtb), conventionally regarded as evidence of latent tuberculosis infection (LTBI), would demonstrate binary responses to preventive therapy (PT), reflecting the differential immunological consequences of the sterilisation of viable infection in those with active Mtb infection versus no Mtb killing

Rationale Host-directed therapeutics for Mycobacterium tuberculosis (Mtb) offer potential strategies for combatting antibiotic resistance and for killing non-replicating bacilli. Phenylbutyrate, a partially selective histone-deacetylase (HDAC) inhibitor, was previously shown to control Mtb growth and alter macrophage inflammatory pathways at 2–4 mM concentrations. Objective To identify a more potent

In this paper, a highly sensitive and specific technique based on the principle of giant magnetoresistance (GMR) has been proposed for the early stage Tuberculosis (TB) diagnostics. This GMR biosensing assay employs monoclonal antibodies against M. tuberculosis specific ESAT-6 antigen with the use of magnetic nanoparticles (MNPs) as labels. MNPs bind to the GMR sensor in presence of ESAT-6 and the

Tuberculosis (TB) is a global health problem, being prevalent in the developing countries. A rapid, reliable and cost effective diagnostic method would help in controlling TB in the endemic populations. Development of suitable fusion molecules detecting multiple antibodies produced against Mycobacterium tuberculosis antigens would enhance sensitivity of serodiagnostic assays. In this study, EspC, CFP7

Tuberculosis remains a serious global health problem. BCG is the only prophylactic TB vaccine and it shows variable protective efficacy. Chimeric protein subunit vaccines hold great potential as stand-alone vaccines or heterologous BCG prime boosters. We have designed a protein chimera, PP31, by combining Mtb ESAT-6 family antigen Rv1198 and MoCo biosynthesis family antigen Rv3111. Further, PP31 was

A limited sampling strategy (LSS) to estimate the exposure to isoniazid was developed considering N-acetyltransferase 2 (NAT2) genotypes in Korean patients with tuberculosis. The influence of the genotypes on the pharmacokinetics of isoniazid was also evaluated. A total of 33 participants participated in the study and received isoniazid 300 mg once daily. Evaluable participants consist of ten slow

BACKGROUND We evaluated the performance of pyrosequencing, a genotypic test which detects TB and XDR-defining mutations within 6 h, directly on CSF samples for diagnosing TB meningitis(TBM). METHODS This retrospective, diagnostic accuracy study was conducted in Hinduja hospital, Mumbai from May-2017 to May-2019. 107 consecutive patients with physician-suspected TBM for whom CSF pyrosequencing was requested

Human macrophages play a major role in controlling tuberculosis (TB), but their anti-mycobacterial mechanisms remain unclear among individuals with metabolic alterations like obesity (TB protective) or diabetes (TB risk). To help discern this, we aimed to: i) Evaluate the impact of the host's TB status or their comorbidities on the anti-mycobacterial responses of their monocyte-derived macrophages

RNASeq analysis of PBMCs from treatment naïve TB patients and healthy controls revealed that M. tuberculosis (Mtb) infection dysregulates several metabolic pathways and upregulates BNIP3L/NIX receptor mediated mitophagy. Analysis of publicly available transcriptomic data from the NCBI-GEO database indicated that M. bovis (BCG) infection also induces similar rewiring of metabolic and mitophagy pathways

BACKGROUND Tuberculosis is chronic infection caused by Mycobacterium tuberculosis (M.tb), which infects specifically macrophages. Hif-1, hypoxia-inducible factor-1, was reported to act as master regulator of killing functions in macrophages. AIM To investigate whether Hif-1 activation would enhance bactericidal effect of macrophages and anti-tuberculosis effect of chemical reagent. METHODS Hif-1 and

Although treatable with antibiotics, tuberculosis is a leading cause of death. Mycobacterium tuberculosis antibiotic resistance is becoming increasingly common and disease control is challenging. Conventional drug susceptibility testing takes weeks to produce results, and treatment is often initiated empirically. Therefore, new methods to determine drug susceptibility profiles are urgent. Here, we

Tuberculosis infection activates the autoimmune system. However, the role of host-pathogen interactions involved in Mycobacterium tuberculosis infection is unclear. In this study, we analyzed 6 spinal tuberculosis tissues and 6 herniated disc tissues by using liquid chromatography-tandem mass spectrometry coupled with tandem mass spectrometry, and immunohistochemical staining was performed for validating

BACKGROUND Symptoms of infectious respiratory illnesses are often assumed to drive transmission. However, production and release of Mycobacterium tuberculosis (Mtb) bioaerosols is poorly understood. We report quantitation of Mtb exhaled during specific respiratory manoeuvres. METHODS Direct capture of nascent bioaerosol particles and indirect collection of aged particles was performed in 10 healthy

Two proof of concept clinical trials with TB vaccines demonstrate that new approaches can prevent sustained TB infection in adolescents (BCG revaccination) and TB disease in adults (M72/ASO1E) (Nemes et al., 2018; Tait et al., 2019) [1,2]. Both approaches are in late stage development and provide motivation and rationale to invest into a global TB vaccine pipeline. This pipeline needs to be diverse

Tuberculosis (TB) was a large burden of infections that peaked during the 19th century in Europe. Mummies from the 18th century CE, discovered in the crypt of a church at Vác, Hungary, had high TB prevalence, as revealed by amplification of key fragments of TB DNA and genome-wide TB analysis. Complementary methods are needed to confirm these diagnoses and one approach uses the identification of specific

OBJECTIVE To elucidate disease-specific host protein profile in vitreous fluid of patients with intraocular inflammation due to tubercular uveitis (TBU). METHODS Vitreous samples from 13 patients with TBU (group A), 7 with non-TBU (group B) and 9 with no uveitis (group C) were analysed by shotgun proteomics using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Differentially expressed proteins