Intracellular tubercle bacilli (TB) reside in vacuoles in infected human macrophages (MPs). The relative impotency of streptomycin against TB in MPs and the contrary greatly increased potency of pyrazinamide (PZA) have been attributed to the fact that these vacuoles are phagolysosomes and, therefore, acidic. Chloroquine (CQ) is a lysomotropic base which can be used to raise phagolysosomal pH. C...

The resurgence of tuberculosis along with the increased resistance of Mycobacterium tuberculosis has emphasized the need for timely susceptibility testing for control of the disease. Previous studies have shown that rapid susceptibility testing can be accomplished for isoniazid, ethambutol, and rifampin using the flow cytometric assays. In this study we compared the flow cytometric susceptibili...

Quinolinic acid phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) is a key enzyme in the de novo pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis and a target for the development of new anti-tuberculosis drugs. QAPRTase catalyzes the synthesis of nicotinic acid mononucleotide from quinolinic acid (QA) and 5-phosphoribosyl-1-pyrophosphate (PRPP) through a phosphoribosyl transfer r...

Pyrazinamide (PZA) is a critical component of first- and second-line treatments of tuberculosis (TB), yet its mechanism of action largely remains an enigma. We carried out a genetic screen to isolate Mycobacterium bovis BCG mutants resistant to pyrazinoic acid (POA), the bioactive derivative of PZA, followed by whole genome sequencing of 26 POA resistant strains. Rather than finding mutations i...

*Corresponding author: Mailing address: International Medical Center of Japan, Toyama 1-21-1, Shinjuku-ku, Tokyo 162-8655, Japan. Fax: +81-3-3202-7364, E-mail: [email protected] Multidrug-resistant tuberculosis (MDR-TB) resulting from failure to control primary tuberculosis (1) poses a serious clinical problem. Understanding how an organism can acquire resistance to multiple drugs is esse...

TO THE EDITOR—We read with interest the recent article by Kurbatova et al [1]. Pyrazinamide (PZA) is a key component of multidrug antituberculosis therapy, in both firstand second-line regimens. In their article, Kurbatova and colleagues underscore the public health importance of describing the epidemiology of PZAresistantMycobacterium tuberculosis (MTB) infection in the United States. Resistan...

The technical limitations of common tests used for detecting pyrazinamide (PZA) resistance in Mycobacterium tuberculosis isolates pose challenges for comprehensive and accurate descriptions of drug resistance in patients with multidrug-resistant tuberculosis (MDR-TB). In this study, a 606-bp fragment (comprising the pncA coding region plus the promoter) was sequenced using Ion Torrent next-gene...

BACKGROUND & OBJECTIVES Concomitant feeding and anti-tuberculosis (TB) drug administration are likely to reduce nausea and enhance compliance to treatment. However, food could lower plasma drug concentrations. This study was undertaken to examine the effect of food on two-hour plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA), and pharmacokinetics of these drugs ...

OBJECTIVE To determine the extent of drug resistance in multidrug-resistant tuberculosis (MDR-TB) cases, we conducted a retrospective, population-based analysis using drug susceptibility testing (DST) results of MDR Mycobacterium tuberculosis complex isolates obtained from 2007-2014 in Taiwan. METHODS M. tuberculosis isolates collected from 1,331 MDR-TB cases were included in this survey. Tre...

Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)-positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the n...