Rufomycin Targets ClpC1 Proteolysis in Mycobacterium tuberculosis and M. abscessus.

ClpC1 is an emerging new target for the treatment of infections, and several cyclic peptides (ecumicin, cyclomarin A, and lassomycin) are known to act on this target. This study identified another group of peptides, the rufomycins (RUFs), as bactericidal to through the inhibition of ClpC1 and subsequent modulation of protein degradation of intracellular proteins. Rufomycin I (RUFI) was found to be a potent and selective lead compound for both (MIC, 0.

Comparison of immunogenicity and vaccine efficacy between heat-shock proteins, HSP70 and GrpE, in the DnaK operon of Mycobacterium tuberculosis.

Antigens (Ags) in Mycobacterium tuberculosis (Mtb) that are constitutively expressed, overexpressed during growth, essential for survival, and highly conserved may be good vaccine targets if they induce the appropriate anti-Mtb Th1 immune response. In this context, stress response-related antigens of Mtb might serve as attractive targets for vaccine development as they are rapidly expressed and are up-regulated during Mtb infection in vivo. Our group recently demonstrated that GrpE, encoded by rv0351 as a cofactor of heat-shock protein 70 (HSP70) in the DnaK operon, is a novel immune activator that interacts with DCs to generate Th1-biased memory T cells in an antigen-specific manner.

Immunomodulating role of IL-10-producing B cells in Leishmania amazonensis infection.

This work aims to study the immunomodulation of B lymphocytes during L. amazonensis infection. We demonstrated in this study that follicular B cells from draining lymph nodes of infected wild type BALB/c mice are the major source of IL-10 during infection.

Human Kinetoplastid Protozoan Infections: Where Are We Going Next?

Kinetoplastida trypanosomatidae microorganisms are protozoan parasites exhibiting a developmental stage in the gut of insect vectors and tissues of vertebrate hosts. During the vertebrate infective stages, these parasites alter the differential expression of virulence genes, modifying their biological and antigenic properties in order to subvert the host protective immune responses and establish a persistent infection. One of the hallmarks of kinetoplastid parasites is their evasion mechanisms from host immunity, leading to disease chronification.

Detection of Rifampicin- and Isoniazid-Resistant Mycobacterium tuberculosis Using the Quantamatrix Multiplexed Assay Platform System.

Background: The increasing prevalence of drug-resistant tuberculosis (TB) infection represents a global public health emergency. We evaluated the usefulness of a newly developed multiplexed, bead-based bioassay (Quantamatrix Multiplexed Assay Platform [QMAP], QuantaMatrix, Seoul, Korea) to rapidly identify the Mycobacterium tuberculosis complex (MTBC) and detect rifampicin (RIF) and isoniazid (INH) resistance-associated mutations.

Methods: A total of 200 clinical isolates from respiratory samples were used.

Performance of an Xpert-based diagnostic algorithm for the rapid detection of drug-resistant tuberculosis among high-risk populations in a low-incidence setting.

Timely diagnosis of drug-resistant tuberculosis (DR-TB) is beneficial for case treatment and management. We implemented an algorithm to improve molecular diagnostic utilization to intensify DR-TB case findings. The GeneXpert MTB/RIF (Xpert) test was used for initial diagnosis.

Role of Hormonal Circuitry Upon T Cell Development in Chagas Disease: Possible Implications on T Cell Dysfunctions.

T cell response plays an essential role in the host resistance to infection by the protozoan parasite , the causative agent of Chagas disease. This infection is often associated with multiple manifestations of T cell dysfunction, both during the acute and the chronic phases of disease. Additionally, the normal development of T cells is affected.

Urine IP-10 as a biomarker of therapeutic response in patients with active pulmonary tuberculosis.

Background: Prior to clinical trials of new TB drugs or therapeutic vaccines, it is necessary to develop monitoring tools to predict treatment outcomes in TB patients. Urine interferon gamma inducible protein 10 (IP-10) is a potential biomarker of treatment response in chronic hepatitis C virus infection and lung diseases, including tuberculosis. In this study, we assessed IP-10 levels in urine samples from patients with active TB at diagnosis, during treatment, and at completion, and compared these with levels in serum samples collected in parallel from matched patients to determine whether urine IP-10 can be used to monitor treatment response in patients with active TB.

Validation and comparison of ELISA kits to measure interferon gamma responses in QuantiFERON cultural supernatants for diagnosis of tuberculosis.

Much effort has been made to reduce the cost of LTBI diagnosis with equivalent efficacy and efficiency of interferon-γ release assay (IGRA). This study showed that repeatability, intermediate precision, and accuracy of the Bionote-ELISA were comparable to QFT-ELISA. The Bionote-ELISA could provide the alternative method.

Patterns of rpoC Mutations in Drug-Resistant Mycobacterium tuberculosis Isolated from Patients in South Korea.

Background: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB.

Extensively drug-resistant tuberculosis in Myanmar: burden and mutations causing second-line drug resistance.

Setting: Two tuberculosis (TB) reference laboratories in Myanmar.

Objectives: To determine the proportion of extensively drug-resistant TB (XDR-TB) cases among multidrug-resistant TB (MDR-TB) cases and the mutations that cause resistance to second-line drugs in Myanmar.

Design: This was a cross-sectional, retrospective study.

Carbon monoxide poisoning in Iran during 1999-2016: A systematic review and meta-analysis.

Background: Carbon monoxide (CO) poisoning is a common cause of emergency department (ED) visits worldwide with high levels of morbidity and mortality. No inclusive nationally statistics of CO poisoning in Iran is available. The present review aimed to describe and review the pattern of CO poisoning in Iran.

Urinary versus plasma neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of mortality for acute kidney injury in intensive care unit patients.

Objective: To examine urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL) levels in predicting ICU mortality.

Design: Prospective observational.

Setting: University Critical Care setting.

Host blood RNA signatures predict the outcome of tuberculosis treatment.

Biomarkers for tuberculosis treatment outcome will assist in guiding individualized treatment and evaluation of new therapies. To identify candidate biomarkers, RNA sequencing of whole blood from a well-characterized TB treatment cohort was performed. Application of a validated transcriptional correlate of risk for TB revealed symmetry in host gene expression during progression from latent TB infection to active TB disease and resolution of disease during treatment, including return to control levels after drug therapy.

Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis.

Background: Fluoroquinolones and second-line injectable drugs are the backbone of treatment regimens for multidrug-resistant tuberculosis, and resistance to these drugs defines extensively drug-resistant tuberculosis. We assessed the accuracy of an automated, cartridge-based molecular assay for the detection, directly from sputum specimens, of Mycobacterium tuberculosis with resistance to fluoroquinolones, aminoglycosides, and isoniazid.

Methods: We conducted a prospective diagnostic accuracy study to compare the investigational assay against phenotypic drug-susceptibility testing and DNA sequencing among adults in China and South Korea who had symptoms of tuberculosis.

Molecular screening of multidrug-resistance tuberculosis by a designated public health laboratory in Taiwan.

This manuscript describes our experience in early identifying MDR-TB cases in high-risk populations by setting up a single-referral molecular diagnosis laboratory in Taiwan. Taiwan Centers for Disease Control designated a single-referral laboratory to provide the GenoType MTBDRplus test for screening high-risk MDR-TB populations nationwide in 2012-2015. A total of 5,838 sputum specimens from 3,308 patients were tested within 3 days turnaround time.

TNF-α-Induced NOD2 and RIP2 Contribute to the Up-Regulation of Cytokines Induced by MDP in Monocytic THP-1 Cells.

Nucleotide-binding oligomerization domain containing 2 (NOD2)-induced signal transduction and cytokine production is regulated by a number of factors. However, the feedback effect of the pro-inflammatory TNF-α on NOD2-induced inflammation is not fully understood. In this study, we found unexpectedly that TNF-α up-regulated NOD2 ligand MDP-induced production of the CXC chemokines, including CXCL1, 2, and 8, and the pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, in a dose-dependent manner at both mRNA and protein levels in monocytic THP-1 cells.

Comparison of the characteristics of Mycobacterium tuberculosis isolates from sputum and lung lesions in chronic tuberculosis patients.

Mycobacterium tuberculosis (Mtb) in sputum originates from lung cavities in tuberculosis (TB) patients. But drug susceptibility testing (DST) of sputum Mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. This could be one of the reasons for low cure rates for multi-drug resistant (MDR)-TB.

Using genotyping to delineate tuberculosis transmission in long-term care facilities: single facility 4-year experience.

Background: Residents in long-term care facilities (LTCFs) are vulnerable to tuberculosis (TB) transmission; however, to delineate possible routes of TB transmission in LTCFs is difficult. This study aimed to address the use of regular genotyping surveillance to delineate TB transmission in LTCFs.

Methods: All of Mycobacterium tuberculosis isolates in the reported 620-bed LTCF between July 2011 and August 2015 were genotyped, and we retrospectively compared epidemiological data and genotyping results.

Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa.

Determining the Frequencies of Th9 Cells from Whole Blood.

Th9 cells are a subset of CD4+ T cells producing the cytokine, IL-9. Th9 cells are increasingly recognized as being important player in allergy, autoimmunity, and antitumor responses. The polarization and expansion of Th9 cells requires the cytokines IL-4, TGF-β.

Accurate and effective multidrug-resistant Mycobacterium tuberculosis detection method using gap-filling ligation coupled with high-resolution capillary electrophoresis-based single strand conformation polymorphism.

Tuberculosis (TB) has severely threatened public health via emerging multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (MTB) strains. For effective TB treatment, rapid, accurate, and multiplex detection of drug resistance is extremely important. However, conventional methods for TB diagnosis are time consuming and have a limited effect on treatment.