Tuberculosis.

Tuberculosis is a leading cause of death globally. Given the airborne transmission of tuberculosis, anybody can be infected, but people in high-incidence settings are more exposed. Risk of progression to disease is higher in the first years after infection, and in people with undernourishment, immunosuppression, or who smoke, drink alcohol, or have diabetes.

Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis in Vietnam.

Background: Prevention of drug-resistant tuberculosis is a global health priority. However, trials evaluating the effectiveness of treating infection among contacts of persons with drug-resistant tuberculosis are lacking.

Methods: We conducted a double-blind, randomized, controlled trial comparing 6 months of daily levofloxacin (weight-based doses) with placebo to treat infection.

Rational Exploration of 2,4-Diaminopyrimidines as DHFR Inhibitors Active against and , Two Emerging Human Pathogens.

Nontuberculous mycobacteria (NTM) are emerging human pathogens linked to severe pulmonary diseases. Current treatments involve the prolonged use of multiple drugs and are often ineffective. Bacterial dihydrofolate reductase (DHFR) is a key enzyme targeted by antibiotics in Gram-negative bacterial infections.

Discovery of benzo[c]phenanthridine derivatives with potent activity against multidrug-resistant .

(Mtb), the pathogen responsible for tuberculosis (TB), is the leading cause of bacterial disease-related death worldwide. Current antibiotic regimens for the treatment of TB remain dated and suffer from long treatment times as well as the development of drug resistance. As such, the search for novel chemical modalities that have selective or potent anti-Mtb properties remains an urgent priority, particularly against multidrug-resistant (MDR) Mtb strains.

Alveolar macrophage function is impaired following inhalation of berry e-cigarette vapor.

In the lower respiratory tract, the alveolar spaces are divided from the bloodstream and the external environment by only a few microns of interstitial tissue. Alveolar macrophages (AMs) defend this delicate mucosal surface from invading infections by regularly patrolling the site. AMs have three behavior modalities to achieve this goal: extending cell protrusions to probe and sample surrounding areas, squeezing the whole cell body between alveoli, and patrolling by moving the cell body around each alveolus.

Implications of subclinical tuberculosis for vaccine trial design and global effect.

Tuberculosis is a leading cause of death from an infectious agent globally. Infectious subclinical tuberculosis accounts for almost half of all tuberculosis cases in national tuberculosis prevalence surveys, and possibly contributes to transmission and might be associated with morbidity. Modelling studies suggest that new tuberculosis vaccines could have substantial health and economic effects, partly based on the assumptions made regarding subclinical tuberculosis.

Genetic and chemical control of tuberculostearic acid production in subspecies .

Tuberculostearic acid (TBSA) is a fatty acid unique to mycobacteria and some corynebacteria and has been studied due to its diagnostic value, biofuel properties, and role in membrane dynamics. In this study, we demonstrate that TBSA production can be abrogated either by addition of pivalic acid to mycobacterial growth cultures or by a gene knockout encoding a flavin adenine dinucleotide (FAD)-binding oxidoreductase. subspecies () growth and TBSA production were inhibited in 0.

Complete genome sequence of an ovine ancestral strain of subspecies 6756.

The complete genome sequence of the most ancestral type SI strain of subspecies 6756, isolated from a sheep, was determined. The genome was sequenced using PacBio technology, yielding a genome size of 4,830,294 nucleotides with no identified plasmids.

Challenging the gold standard: the limitations of molecular assays for detection of heteroresistance.

Objectives: Heteroresistant infections are defined as infections in which a mixture of drug-resistant and drug-susceptible populations are present. In (), heteroresistance poses a challenge in diagnosis and has been linked with poor treatment outcomes. We compared the analytical sensitivity of molecular methods, such as GeneXpert and whole genome sequencing (WGS) in detecting heteroresistance when compared with the 'gold standard' phenotypic assay: the agar proportion method (APM).

Molecular detection and characterization of the complex subspecies responsible for bovine tuberculosis in Punjab, Pakistan.

Bovine tuberculosis (bTB), traditionally associated with , presents significant public health and economic challenges worldwide. This study investigated the causative agents of bTB in slaughtered cattle and buffalo in Lahore, Pakistan. Of the 3,581 animals screened, 34 were identified with gross TB-like lesions.

An imputed ancestral reference genome for the complex better captures structural genomic diversity for reference-based alignment workflows.

Reference-based alignment of short-reads is a widely used technique in genomic analysis of the complex (MTBC) and the choice of reference sequence impacts the interpretation of analyses. The most widely used reference genomes include the ATCC type strain (H37Rv) and the putative MTBC ancestral sequence of Comas both of which are based on a lineage 4 sequence. As such, these reference sequences do not capture all of the structural variation known to be present in the ancestor of the MTBC.

Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment.

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a chronic gastrointestinal disease affecting ruminants. This disease remains widespread in part due to the limitations of available diagnostics and vaccines.

An Aspiration to Radically Shorten Phase 3 Tuberculosis Vaccine Trials.

A new tuberculosis vaccine is a high priority. However, the classical development pathway is a major deterrent. Most tuberculosis cases arise within 2 years after Mycobacterium tuberculosis exposure, suggesting a 3-year trial period should be possible if sample size is large to maximize the number of early exposures.

A nod to the bond between NOD2 and mycobacteria.

Mycobacteria are responsible for several human and animal diseases. NOD2 is a pattern recognition receptor that has an important role in mycobacterial recognition. However, the mechanisms by which mutations in NOD2 alter the course of mycobacterial infection remain unclear.