Drug susceptibility testing and line probe assay of first-line anti-tuberculosis drugs among presumptive tuberculosis patients attending a secondary care hospital in Bhubaneswar.

Background: Pyrazinamide (PZA) is important for identification in multi-drug-resistant tuberculosis patients before starting therapy. PZA drug susceptibility testing (DST) is essential for the management of drug-resistant and susceptible TB patients. Aims: The degree of drug resistance among TB patients and discrepancy between DST results of the phenotype and genotype were assessed. Materials and Methods: Socio-demographic and clinical profiles of TB patients recruited in the study were documented. Sputum samples were processed for diagnosis using TrueNat Xpert MTB, TrueNat Xpert MTB Plus, and MGIT culture. Results: Rifampicin (RIF) line probe assay (LPA) showed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100%, whereas isoniazid (INH) LPA testing showed a sensitivity of 85.7%, a specificity and PPV of 100%, and NPV of 94.8%. The gene mutation for RIF resistance was between the codon, 530-533 of rpoB gene, and that for INH resistance was at the codon, 315 of katG gene. Conclusion: Our findings demonstrated high prevalence of mono- and poly-drug resistance as well as pyrazinamide resistance.

A Comparative Investigation on Cytokine Expression in Pulmonary Tuberculosis and Comorbidity with Type 2 Diabetes Mellitus.

BACKGROUND: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), with a high global prevalence and mortality rate. To control the gruesome pathogen, a deep understanding of pathophysiology and host-pathogen interaction is essential for early diagnosis and novel drug development. Cytokines play a crucial role in infection and susceptibility, and their expressions could serve as potential biomarkers to enhance our understanding of Mtb pathophysiology for improved therapeutic approaches. This cross-sectional study investigates the levels of four important T-cell immune-mediated cytokines: interleukins (IL-6 and IL-10), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha in 80 cohort samples, with 20 people in each group. METHODS: Following proper ethics and patient consent, we collected blood samples and isolated serum from all four groups: TB, type 2 diabetes mellitus (T2DM), type 2 diabetes-TB comorbidity (T2DM + TB), and a healthy individual as a control group (C). Furthermore, cytokine expression was measured in individual serum samples through the enzyme-linked immunosorbent assay method using commercial kits (Diaclone, French). Statistical significance was observed by analyzing triplicate data using t-tests and the one-way ANOVA method with GraphPad Prism 10. RESULTS: The results showed that all four cytokine levels were higher (P ≤ 0.0001) than the control, especially IL-6, IL-10, and IFN-γ, which were found to be upregulated in T2DM + TB samples (P ≤ 0.0001) than individual TB or T2DM samples. CONCLUSION: The high levels of cytokines in comorbidity cases raise the risk of insulin resistance and the severity of TB infection. These levels of expression could be used to keep track of the Mtb infection status or severity, aid in early diagnosis as a possible biomarker, and suggest possible treatment plans.

Drug resistance reversal potential of multifunctional thieno[3,2-c]pyran via potentiation of antibiotics in MDR P. aeruginosa.

We explored the antibacterial potential (alone and combination) against multidrug resistant (MDR) Pseudomonas aeruginosa isolates KG-P2 using synthesized thieno[3,2-c]pyran-2-ones in combination with different antibiotics. Out of 14 compounds, two compounds (3g and 3l) abridged the MIC of tetracycline (TET) by 16 folds. Compounds was killing the KG-P2 cells, in time dependent manner, lengthened post-antibiotic effect (PAE) of TET and found decreased the mutant prevention concentration (MPC) of TET. In ethidium bromide efflux experiment, two compounds repressed the drug transporter (efflux pumps) which is further supported by molecular docking of these compounds with efflux complex MexAB-OprM. In another study, these compounds inhibited the synthesis of biofilm.

Drug Resistance Reversal Potential of Nanoparticles/Nanocomposites via Antibiotic's Potentiation in Multi Drug Resistant P. aeruginosa.

Bacteria employ numerous resistance mechanisms against structurally distinct drugs by the process of multidrug resistance. A study was planned to discover the antibacterial potential of a graphene oxide nanosheet (GO), a graphene oxide-zinc oxide nanocomposite (GO/ZnO), a graphene oxide-chitosan nanocomposite (GO-CS), a zinc oxide decorated graphene oxide-chitosan nanocomposite (GO-CS/ZnO), and zinc oxide nanoparticles (ZnO) alone and in a blend with antibiotics against a PS-2 isolate of Pseudomonas aeruginosa. These nanocomposites reduced the MIC of tetracycline (TET) from 16 folds to 64 folds against a multidrug-resistant clinical isolate. Efflux pumps were interfered, as evident by an ethidium bromide synergy study with nanocomposites, as well as inhibiting biofilm synthesis. These nanoparticles/nanocomposites also decreased the mutant prevention concentration (MPC) of TET. To the best of our knowledge, this is the first report on nanomaterials as a synergistic agent via inhibition of efflux and biofilm synthesis.

Therapeutic Potential of Endophytic Compounds: A Special Reference to Drug Transporter Inhibitors.

From the discovery to the golden age of antibiotics (miracle), millions of lives have been saved. The era of negligence towards chemotherapeutic agents gave birth to drug resistance. Among all the regulators of drug resistance, drug transporters are considered to be the key regulators for multidrug resistance. These transporters are prevalent from prokaryotes to eukaryotes. Endophytes are one of the unexplored wealths of nature. Endophytes are a model mutualistic partner of plants. They are the reservoir of novel therapeutics. The present review deals with endophytes as novel drug resistance reversal agents by inhibiting the drug transporters across the genera. This review also focuses on drug transporters, and mutualistic chemical diversity, exploring drug transporter modulating potential of endophytes.