Biology subjects

Ngugi, M. P.

Publications and source records attributed to Ngugi, M. P..

3 recordsLinked to original sources

bioRxiv2026

Natural product-based putative efflux inhibitors restore bedaquiline susceptibility in a drug-resistant Mycobacterium tuberculosis mutant

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a potent threat to global public health. Moreover, the alarming surge in the number of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains will continue to imperil TB control efforts. Thus, the discovery of new TB agents with novel modes of action or resistance-reversing therapeutics is a pressing priority. In this study, we report the generation of spontaneous Mtb mutants exhibiting bedaquiline (BDQ) resistance and the subsequent evaluation of natural product-derived efflux inhibitors (EIs) that restored the antimicrobial efficacy of BDQ against the mutants. BDQ-resistant mutants were successfully isolated, and colonies were observed on agar plates with concentrations up to 100x the minimum inhibitory concentration (MIC). Upon screening against BDQ, the resistant strains exhibited MIC values ranging from 0.098 M to 3.136 M, corresponding to 1-32-fold increases relative to the wild type, with higher resistance observed on 50x- and 100x-selection plates. Genetic analysis identified point mutations and frameshifts in key resistance-related genes, including Rv0678, pepQ, and atpE. Notably, combining BDQ with EIs such as berberine (BER), reserpine (RES), piperine (PIP), and lyoniresinol (LYO) remarkably lowered the MIC in the selected mutant strain. Synergistic effects were observed for BDQ+BER (FICI = 0.188; 16-fold MIC reduction) and BDQ+RES (FICI = 0.37; 8-fold MIC reduction). For BDQ+LYO, the FICI could not be calculated because LYO did not have an MIC at the highest concentration tested; however, this combination produced the strongest effect, restoring susceptibility with a 64-fold MIC reduction and exhibiting bactericidal activity. These results highlight the role of efflux pumps in BDQ resistance and support the use of natural product-derived EIs as potential supplementary therapies against drug-resistant Mtb.

microbiology↗

bioRxiv2023

Overexpressing the IPT gene improves drought tolerance and nutritional value of tropical maize (Zea mays L.)

Drought stress poses a significant threat to crop productivity, making the development of drought-tolerant crops a priority. The impact of drought on grain yield loss varies significantly, ranging from 10% to 76%, depending on the specific stage of occurrence and the severity of the drought. In this study, we investigated the effects of introducing the pSARK::IPT transgene on the drought tolerance and nutritional composition of successive generations of tropical maize. Towards this goal, we screened different generations of maize plants by genotyping PCR, exposed them to long term drought stress and analysed several drought stress markers and nutritional profiles of the plants. Our results demonstrated that the pSARK::IPT transgene was present in 4 successive generations of maize plants. Under drought conditions, transgenic maize exhibited higher relative water content, and delayed senescence compared to wild-type plants. Additionally, transgenic plants showed increased levels of total chlorophyll, chlorophyll a, and chlorophyll b, indicating improved photosynthetic activity under water deficit. Our study also showed that IPT-transgenic plants produced substantially higher yields and demonstrated enhanced nutritional value compared to wildtype plants when grown under well-watered conditions. Further research is warranted to investigate the underlying molecular mechanisms involved in these improvements and assess the performance of pSARK::IPT maize under field conditions.

bioengineering↗

bioRxiv2019

Effects of DCM leaf Extract of Gnidia glauca (Fresen) on Locomotor Activity, Anxiety and Exploration-Like Behaviors in High Fat Diet-Induced Obese Rats

Obesity is the main component of metabolic syndromes involving distinct etiologies which target different underlying behavioral and physiological functions within the brain structures and neuronal circuits. An alteration in the neuronal circuitry stemming from abdominal or central obesity stimulates a cascade of changes in neurochemical signaling that directly or indirectly mediate spontaneously emitted behaviors such as locomotor activity patterns, anxiety and exploration. Pharmacological agents available for the treatment of neurologic disorders have been associated with limited potency and intolerable adverse effects. These have necessitated the upsurge in utilization of herbal prescriptions due to their affordability, easy accessibility and are firmly embedded within wider belief systems of many people. Gnidia glauca has been used in management of many ailments including obesity and associated symptomatic complications. However, its upsurge in use has not been accompanied with authentication of these folkloric claims. The present study aimed to determine the modulatory effect of Dichloromethane leaf extract of Gnidia glauca on locomotor activity, exploration and anxiety-like behaviors in high fat diet-induced obese rats in an Open Field Arena. Obesity was experimentally induced by feeding the rats with prepared high fat diet and water ad libitum for a period of 6 weeks. The in-vivo anti-obesity effects were determined by oral administration of G. glauca at dosage levels of 200, 250 and 300mg/kg body weight in high fat diet-induced obese rats from the 6th to 12th week. Phytochemical analysis was done using gas chromatography linked to mass spectroscopy. Results indicated that Gnidia glauca showed anxiolytic effects and significantly increased spontaneous locomotor activity and exploration-like behaviors in HFD-induced obese rats. The plant extract also contained phytocompounds that have been associated with amelioration of the main neurodegenerative mediators viz inflammation and oxidative stress. These findings provide qualified leads for the synthesis of new alternative therapeutic agent for management of neurologic disorders. However, theres need to conduct toxicity studies of Gnidia glauca to establish its safety profiles.

animal behavior and cognition↗