Antibacterial and Anti-HIV Metabolites from Marine Streptomyces albus MAB56 Isolated from Andaman and Nicobar Islands, India.

Marine-derived actinobacteria have tremendous potential to produce novel metabolites with diverse biological activities. The Andaman coast of India has a lot of microbial diversity, but it is still a relatively unknown ecology for isolating novel actinobacteria with beneficial bioactive compounds. We have isolated 568 actinobacterial strains from mangrove rhizosphere sediments and sponge samples.

In-vivo studies on Transitmycin, a potent Mycobacterium tuberculosis inhibitor.

This study involves the in-vitro and in-vivo anti-TB potency and in-vivo safety of Transitmycin (TR) (PubChem CID:90659753)- identified to be a novel secondary metabolite derived from Streptomyces sp (R2). TR was tested in-vitro against drug resistant TB clinical isolates (n = 49). 94% of DR-TB strains (n = 49) were inhibited by TR at 10μg ml-1.

Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study.

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens.

Adequacy of examining one sputum specimen in tuberculosis drug resistance surveys.

Objective/background: Collection of one spot and one morning sputum specimen is recommended for tuberculosis (TB) drug resistance surveys. This was a retrospective analysis of Mycobacterium tuberculosis cultures isolated from two spot sputum specimens collected from smear positive TB patients in a TB drug resistance survey. It was conducted to understand the value of a second specimen.

Homology modeling, substrate docking, and molecular simulation studies of mycobacteriophage Che12 lysin A.

Mycobacteriophages produce lysins that break down the host cell wall at the end of lytic cycle to release their progenies. The ability to lyse mycobacterial cells makes the lysins significant. Mycobacteriophage Che12 is the first reported temperate phage capable of infecting and lysogenising Mycobacterium tuberculosis.

Drug resistance among extrapulmonary TB patients: Six years experience from a supranational reference laboratory.

Background & Objectives: There is limited information available about the drug resistance patterns in extrapulmonary tuberculosis (EPTB), especially from high burden countries. This may be due to difficulty in obtaining extrapulmonary specimens and limited facilities for drug susceptibility testing. This study was undertaken to review and report the first and second-line anti-TB drug susceptibility patterns in extrapulmonary specimens received at the National Institute for Research in Tuberculosis (NIRT), Chennai, India, between 2005 and 2012.

Revisiting the susceptibility testing of Mycobacterium tuberculosis to ethionamide in solid culture medium.

Background & Objectives: Increase in the isolation of drug resistant phenotypes of Mycobacterium tuberculosis necessitates accuracy in the testing methodology. Critical concentration defining resistance for ethionamide (ETO), needs re-evaluation in accordance with the current scenario. Thus, re-evaluation of conventional minimum inhibitory concentration (MIC) and proportion sensitivity testing (PST) methods for ETO was done to identify the ideal breakpoint concentration defining resistance.

Andrographolide: A potent antituberculosis compound that targets Aminoglycoside 2'-N-acetyltransferase in Mycobacterium tuberculosis.

Tuberculosis (TB) still remains a major challenging infectious disease. The increased rate of emergence of multi-drug resistant and extensively-drug resistant strains of the organism has further complicated the situation, resulting in an urgent need for new anti-TB drugs. Antimycobacterial activity of Andrographis paniculata was evaluated using a rapid LRP assay and the probable targets were identified by docking analysis.

High rates of ofloxacin resistance in Mycobacterium tuberculosis among both new and previously treated patients in Tamil Nadu, South India.

Periodic drug resistance surveillance provides useful information on trends of drug resistance and effectiveness of tuberculosis (TB) control measures. The present study determines the prevalence of drug resistance among new sputum smear positive (NSP) and previously treated (PT) pulmonary TB patients, diagnosed at public sector designated microscopy centers (DMCs) in the state of Tamil Nadu, India. In this single-stage cluster-sampling prevalence survey, 70 of 700 DMCs were randomly selected using a probability-proportional to size method.

Sputum culture conversion with moxifloxacin-containing regimens in the treatment of patients with newly diagnosed sputum-positive pulmonary tuberculosis in South India.

Background: Rapid sputum culture conversion at 2 months indicates the sterilizing capacity and potential of regimens to shorten duration of tuberculosis treatment. We compared results of sputum culture conversion by moxifloxacin and control regimens and identified factors affecting sputum culture positivity after 2 months of treatment.

Methods: Human immunodeficiency virus-uninfected adults with newly diagnosed smear-positive pulmonary tuberculosis were randomized to receive a 3- or 4-month moxifloxacin regimen (moxifloxacin [M], isoniazid [H], rifampicin [R], pyrazinamide [Z], ethambutol [E]) or the control regimen (RHZE thrice weekly).

Stratifying low level Isoniazid resistance using additional intermediate drug concentration.

Isoniazid (INH) susceptibility testing for 100 Mycobacterium tuberculosis performed by conventional minimum inhibitory concentration (MIC) method was stratified using additional drug concentrations. Introduction of additional drug concentrations did not greatly improve the discriminatory capacity, but can be used in specialized studies pertaining to cross resistance between structural analogues of INH.

HIV-infected patients retreated for tuberculosis with intermittent Category II regimen--treatment outcome at 24-month follow-up.

Background: The management of tuberculosis re-treatment in HIV-infected individuals is complex. The clinical and radiological manifestations in this group and response to Category II treatment is not well described.

Methods: We performed a prospective cohort study of HIV-infected patients retreated for TB due to failure, relapse or default after treatment, at Tuberculosis Research Centre, Chennai, between February 2001 to September 2005.

Bioactive Potential of Actinomycetes from Less Explored Ecosystems against Mycobacterium tuberculosis and Other Nonmycobacterial Pathogens.

Bioactive potential of actinomycetes isolated from certain less explored Indian ecosystems against Mycobacterium tuberculosis and other nonmycobacterial pathogens was investigated. Actinomycetes were isolated from the soil samples collected from desert, coffee plantation, rubber forest, and hill area and their cultural and micromorphological characteristics were studied. Crude extracts were prepared by agar surface fermentation and tested against M.

Randomized clinical trial of thrice-weekly 4-month moxifloxacin or gatifloxacin containing regimens in the treatment of new sputum positive pulmonary tuberculosis patients.

Background: Shortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India.

Methods: Newly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C).

Luciferase reporter phage phAE85 for rapid detection of rifampicin resistance in clinical isolates of Mycobacterium tuberculosis.

Objective: To evaluate luciferase reporter phage (LRP) phAE85 in rapid detection of rifampicin resistance in a region where TB is endemic.

Methods: One hundred and ninety primary isolates on Lowenstein-Jensen medium were tested. Middlebrook 7H9 complete medium with and without rifampicin at 2 μg/mL was inoculated with standard inoculum from suspensions of the clinical isolate.

Optimization of the conventional minimum inhibitory concentration method for drug susceptibility testing of ethionamide.

Evaluation of newer methods and optimization of existing methods for the susceptibility testing of second-line drugs, especially ethionamide, are essential when treatment of multidrug-resistant tuberculosis (MDR-TB) is warranted. The ideal method must clearly demarcate sensitive from resistant strains. Hence, optimization of the conventional minimum inhibitory concentration (MIC) method was attempted using diluted inoculum.

Characterization and phylogenetic analysis of antituberculous compound producing actinomycete strain D25 isolated from Thar Desert soil, Rajasthan.

During the course of the anti-infective drug discovery programme, actinomycete strain D25 was recovered from the Thar Desert soil, Rajasthan, India. Actinomycin type of compound isolated from the strain D25 showed promising activity against multi drug resistant and extensively drug resistant M. tuberculosis isolates.

Phage lysin to control the overgrowth of normal flora in processed sputum samples for the rapid and sensitive detection of Mycobacterium tuberculosis by luciferase reporter phage assay.

Background: Phage lysin, extracted from three bacteriophages was used in place of antibiotics to control the overgrowth of normal flora in processed sputum samples leading to the sensitive detection of Mycobacterium tuberculosis using diagnostic luciferase reporter phage assay (DLRPA).

Methods: A total of 129 sputum samples were processed by modified Petroff's method. Two Lowenstein Jensen slopes were inoculated from the processed sputum deposit thus obtained.

Equivalence of acid alone or acid-alcohol as decolourizing agent in Ziehl-Neelsen method.

Background: Microscopists opine that acid-alcohol decolourized slides may enhance acid-fast bacilli (AFB) smear positivity, and published documents on equivalence of acid and acid-alcohol in ZN staining method are not easily accessible.

Setting: National Institute for Research in Tuberculosis, Chennai, India.

Objective: To document the equivalence of 25% sulphuric acid (ZN-acid method) and 3% hydrochloric acid-alcohol (ZN-alcohol method) as decolourizing agents in ZN method for detection of acid-fast bacilli.

Modification of proportion sensitivity testing method for ethionamide.

Standardized methodology for drug susceptibility testing of second line drugs is vital for treatment of multi/extensively drug resistant tuberculosis. Discrepancy between laboratory methods and clinical interpretation is well established for bacteriostatic drugs such as ethionamide. Optimization of the standard proportion sensitivity testing (PST) method for ethionamide was under taken in 235 Mycobacterium tuberculosis isolates from new and previously treated pulmonary tuberculosis patients.

Quality indicators in a mycobacteriology laboratory supporting clinical trials for pulmonary tuberculosis.

Background: Documentation of structured quality indicators for mycobacteriology laboratories supporting exclusively controlled clinical trials in pulmonary tuberculosis (PTB) is lacking.

Objective: To document laboratory indicators for a solid (Lowenstein-Jensen medium) culture system in a mycobacteriology laboratory for a period of 4years (2007-2010).

Methods: The sputum samples, collected from PTB suspects/patients enrolled in clinical trials, were subjected to fluorescence microscopy, culture and drug sensitivity testing (DST).

Microwave-assisted synthesis, molecular docking and antitubercular activity of 1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives.

Based on bioisosteric similarities with isoniazid, a series of 1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives has been designed. The target compounds have been synthesized by multicomponent reaction which involves one-pot organic reactions using ethylcyanoacetate, urea/thiourea and arylaldehydes in presence of ethanolic K(2)CO(3). Two methodologies, conventional and microwave-assisted, have been adopted for the synthesis.

Retrieval of Mycobacterium tuberculosis cultures suspended in phosphate buffered saline.

One hundred and twenty-seven of 130 isolates of Mycobacterium tuberculosis, suspended in phosphate buffered saline (PBS) and stored at ambient conditions in the laboratory for 14days, and another 55 of 60 cultures, suspended as above, transported from reference laboratories within 7days, were successfully retrieved on LJ medium. Considering the maximum retrieval of M. tuberculosis, use of PBS can be explored further for transportation of M.

Performance indicators of fluorescence microscopy for sputum samples in pulmonary tuberculosis.

To get insight into the sensitivity of fluorescence microscopy for diagnostic and follow-up sputum samples from pulmonary tuberculosis patients in clinical trials, the yield of smear positivity - among culture positive sputum samples - encountered in diagnostic and follow-up samples was retrospectively analyzed from the data available in a mycobacteriology laboratory in India. The sensitivity of fluorescence microscopy for diagnostic and follow-up samples respectively was found to be 94.3% and 60.