Biology subjects

Nahid, P.

Publications and source records attributed to Nahid, P..

3 recordsLinked to original sources

bioRxiv2026

Serum nutritional-metabolic recovery during tuberculosis treatment across BMI-defined undernutrition strata: A longitudinal proteomic reanalysis

Background Tuberculosis remains the leading cause of death from a single infectious agent, and undernutrition is a major modifiable risk factor. Serum proteomics can capture systemic host recovery during therapy, but whether baseline BMI-defined undernutrition alters this trajectory is unclear. Methods We reanalysed processed longitudinal tandem-mass-tag serum proteomics from 30 adults with pulmonary tuberculosis and durable cure sampled at baseline and weeks 8, 17, 26 and 52. Thirteen participants had baseline BMI <18.5 kg/m2 and 17 had BMI >=18.5 kg/m2. Protein-level analyses evaluated baseline differences and week-specific within-participant change; module and recovery-axis models evaluated BMI-by-time interactions, with random-intercept mixed models added as a repeated-measures sensitivity analysis. Three complementary treatment-responsive modules were integrated into an exploratory, nonredundant 36-protein nutritional-metabolic summary axis. Results The reconstructed dataset contained 1,923 quantified features across 150 participant-visits. Inflammatory/acute-phase and metal-handling/nutritional-immunity module scores declined during follow-up, whereas lipid/apolipoprotein-transport, nutritional-carrier and endocrine-immunometabolic scores increased. In the primary week-specific paired-change analyses, no protein-level between-BMI difference in longitudinal change survived false-discovery-rate correction; no curated-module BMI-by-time interaction survived correction. The 36-protein summary axis increased in both BMI strata from week 17 onward. In a random-intercept model without interaction, the BMI <18.5 kg/m2 stratum had a lower average axis score across visits than the BMI >=18.5 kg/m2 comparison stratum, although the confidence interval included zero (difference -1.34, 95% CI -2.76 to 0.08; p = .064). Categorical and continuous BMI-by-time interaction tests did not detect differential axis trajectories. Conclusions Tuberculosis treatment was accompanied by broad longitudinal remodelling of circulating inflammatory and nutritional-metabolic protein systems. An exploratory 36-protein summary axis increased in both baseline BMI strata, while formal interaction tests did not detect BMI-dependent trajectories and remained too imprecise to establish equivalence. BMI should be regarded as an anthropometric proxy rather than a comprehensive measure of nutritional state. The defined axis provides a framework for prospective validation alongside direct measures of body composition, micronutrients, treatment exposure and clinical outcomes.

bioinformatics↗

bioRxiv2023

Transcriptional adaptation of drug-tolerant Mycobacterium tuberculosis in mice

Transcriptome evaluation of Mycobacterium tuberculosis in the lungs of laboratory animals during long-term treatment has been limited by extremely low abundance of bacterial mRNA relative to eukaryotic RNA. Here we report a targeted amplification RNA sequencing method called SEARCH-TB. After confirming that SEARCH-TB recapitulates conventional RNA-seq in vitro, we applied SEARCH-TB to Mycobacterium tuberculosis-infected BALB/c mice treated for up to 28 days with the global standard isoniazid, rifampin, pyrazinamide, and ethambutol regimen. We compared results in mice with 8-day exposure to the same regimen in vitro. After treatment of mice for 28 days, SEARCH-TB suggested broad suppression of genes associated with bacterial growth, transcription, translation, synthesis of rRNA proteins and immunogenic secretory peptides. Adaptation of drug-stressed Mycobacterium tuberculosis appeared to include a metabolic transition from ATP-maximizing respiration towards lower-efficiency pathways, modification and recycling of cell wall components, large-scale regulatory reprogramming, and reconfiguration of efflux pumps expression. Despite markedly different expression at pre-treatment baseline, murine and in vitro samples had broadly similar transcriptional change during treatment. The differences observed likely indicate the importance of immunity and pharmacokinetics in the mouse. By elucidating the long-term effect of tuberculosis treatment on bacterial cellular processes in vivo, SEARCH-TB represents a highly granular pharmacodynamic monitoring tool with potential to enhance evaluation of new regimens and thereby accelerate progress towards a new generation of more effective tuberculosis treatment.

microbiology↗

bioRxiv2021

Combination of Mycobacterium tuberculosis RS ratio and CFU improves the ability of murine efficacy experiments to distinguish between drug treatments

Murine tuberculosis drug efficacy studies have historically monitored bacterial burden based on colony forming units of M. tuberculosis in lung homogenate. In an alternative approach, a recently described molecular pharmacodynamic marker called the RS ratio quantifies drug effect on a fundamental cellular process: ongoing ribosomal RNA synthesis. Here we evaluated the ability of different pharmacodynamic markers to distinguish between treatments in three BALB/c mouse experiments at two institutions. We confirmed that different pharmacodynamic markers measure distinct biological responses. We found that a combination of pharmacodynamic markers distinguishes between treatments better than any single marker. The combination of the RS ratio with colony forming units showed the greatest ability to recapitulate the rank order of regimen treatment-shortening activity, providing proof of concept that simultaneous assessment of pharmacodynamic markers measuring different properties will enhance insight gained from animal models and accelerate development of new combination regimens. These results suggest potential for a new era in which antimicrobial therapies are evaluated not only on culture-based measures of bacterial burden but also on molecular assays that indicate how drugs impact the physiological state of the pathogen.

microbiology↗