Biology subjects

Ahmad, H.

Publications and source records attributed to Ahmad, H..

16 recordsLinked to original sources

bioRxiv2026

Restoring Antibiotic Sensitivity via Metabolic Pathway Manipulation in Pseudomonas aeruginosa

Stopping antimicrobial multidrug resistance (AMR) is essential to maintain the efficacy of current treatments and sustain modern medicine, but current control relies on a coordinated One Health approach involving stewardship, infection prevention and other control measures, without direct actionable mechanisms against resistance itself. Here, integrating proteomics and metabolomics with high-throughput Caenorhabditis elegans infection models, we show that unique synergy of biotin biosynthesis inhibition with metformin uncouples virulence from bacterial viability shutting down major Pseudomonas aeruginosa (PA) virulence mechanisms that impair host survival. Under directed evolution induced by central carbon metabolic stress, laboratory and clinical PA strain isolates acquire mutations in the MexAB-OprM multidrug efflux pump, leading to reversal of the AMR phenotype and restored susceptibility to multiple legacy and last-resort antibiotics such as meropenem. Our findings reveal a previously unexploited vulnerability in PA, its co-dependence on biotin biosynthesis and energy metabolism for virulence and resistance. This work establishes a conceptual framework in which metabolic co-targeting can abolish pathogenesis and drive reversal of antimicrobial resistance. It lays the foundation for first-in-class, non-antibiotic PA-selective anti-virulence and resistance-reversing therapies, key to extending the lifesaving duration of existing antibiotics.

microbiology↗

bioRxiv2026

A Type VII-secreted toxin enables inter-mycobacterial competition

Summary ParagraphMost bacteria live in complex environments where resources are scarce and competition is fierce. These organisms have evolved mechanisms to compete with other bacteria, often through the specialised secretion of proteinaceous toxins. Mycobacteria have not previously been reported to engage in this form of competition. The thick and unusual cell wall of mycobacteria, comprised of peptidoglycan, arabinogalactan and mycolic acids, is generally thought to be highly protective to these bacteria. Many enzymes have evolved to maintain this structure, including the GH183 family, which cleaves arabinogalactan. Here, we establish for the first time that some mycobacteria have weaponised a subset of these endo-D-arabinanases to enable inter-bacterial competition. We show that mycobacteria secrete an endo-D-arabinanase effector via the type VII secretion system that specifically targets the arabinogalactan layer of the Mycobacteriales cell envelope. Using structural biology and biochemistry, we identify the molecular basis for this activity and reveal a new protein family that protects the bacterium from the activity of this toxin. Finally, our data uncover widespread T7-secreted toxins in the Mycobacteriales, pointing to extensive inter-mycobacterial competition.

microbiology↗

bioRxiv2026

Chemical genomics screening reveals novel functions for unannotated genes in Vibrio cholerae C6706

Vibrio cholerae, the causative agent of cholera, remains a major global health burden despite ongoing initiatives for vaccination and improved sanitation. Much of the V. cholerae life cycle occurs in aquatic environments, requiring gene functions that enable survival under diverse stresses associated with this niche and during the transition to the human host. Although numerous V. cholerae genome sequences are available, functional annotation across its pan-genome remains incomplete, and many annotated genes lack experimental validation. In this study, we employed a chemical genomics approach to profile fitness phenotypes across 104 diverse stress conditions using a library of 3,026 single-gene mutants of V. cholerae C6706, a widely used research strain. In total, we identified significant growth phenotypes for 1,518 mutants, of which 88 correspond to unannotated (hypothetical or putative) genes. Together, these data provide a comprehensive resource for exploring gene function in V. cholerae, supported by detailed quality metrics and open-access tools to facilitate community-driven discovery. AUTHOR SUMMARYAlthough many bacterial pathogens have been extensively sequenced, we still know relatively little about what many of their genes actually do. In many cases, gene functions are solely predicted by computer algorithms but have not been confirmed in the laboratory, and we can assume that some of those predictions may be incorrect. Chemical genomics -- a method that tests thousands of single-gene mutants under different stresses -- can help reveal what these genes are responsible for. Using this approach, we screened a library of Vibrio cholerae C6706 mutants under 104 different conditions. We found that more than half of the mutants showed measurable effects on growth, including many genes that were previously uncharacterized. Here, we describe our experimental pipeline, present key quality checks, and share how other researchers can use this dataset as a resource to explore V. cholerae mutant phenotypes.

systems biology↗

bioRxiv2025

ChemGenXplore: An Interactive Tool for Exploring and Analysing Chemical Genomic Data

MotivationChemical genomics is a useful high-throughput approach to systematically link phenotypes to genotypes. However, the vast datasets generated remain challenging to explore due to the lack of integrated, interactive tools for visualisation and analysis. Existing workflows often require multiple independent software tools, limiting data accessibility and collaboration. Therefore, we created a user-friendly platform that enable efficient exploration and sharing of chemical genomics data. ResultsWe developed ChemGenXplore, a web-based Shiny application designed to streamline the visualisation and analysis of chemical genomic screens. It offers two primary functionalities: one for exploring pre-implemented datasets and another for analysing user-uploaded datasets. ChemGenXplore enables users to visualise phenotypic profiles, assess gene-gene and condition-condition correlations, perform GO and KEGG enrichment analysis, and generate customisable, interactive heatmaps. By consolidating these features into an interactive and accessible tool, ChemGenXplore facilitates data sharing, enhances reproducibility, and promotes collaboration within the research community. Availability and ImplementationChemGenXplore is freely accessible as a web application at https://chemgenxplore.kaust.edu.sa/ and is also available for local deployment via GitHub at https://github.com/Hudaahmadd/ChemGenXplore.

bioinformatics↗

bioRxiv2024

PARP inhibition enhances exemestane efficacy in triple-negative breast cancer

Triple negative breast cancer (TNBC) remains the breast cancer subtype with the poorest prognosis and median survival rate. Targeting PARP1/2 with PARP inhibitors (PARPi) and achieving synthetic lethality is an effective strategy for TNBCs with BRCA1/2 mutations, however, the majority of TNBCs are BRCA1/2 wild type. Synergistic drug combinations with PARPi offers the potential to expand the use of PARPi towards BRCA-proficient cancers, including TNBC. To identify new PARPi combinations, we screened a library of 166 FDA-approved oncology drugs for synergy with the PARPi Olaparib in TNBC cells. We found that Exemestane, an aromatase inhibitor, synergised with Olaparib with a significant decrease in IC50 values and clonogenicity accompanied by elevated DNA damage and apoptosis seen in combination treatment. The mechanistic basis for synergy was rationalised by the previously unreported ability of Exemestane to induce replication stress, as evidenced by ATR pathway activation and RPA foci formation. Low impact of this combination towards normal breast epithelial cells was observed and Exemestane has no reported severe toxicity as a monotherapy. This combination was able to achieve enhanced tumor growth inhibition in a murine xenograft model, greater than either drug employed as a single-agent. GO and KEGG enrichment analysis of differential genes indicated alterations in pathways associated with cell death in response to Exemestane and Olaparib treatment.

pharmacology and toxicology↗

bioRxiv2024

Detection of Echinococcus spp. and other taeniid species in lettuces and berries: two international multicenter studies from the MEmE project

Cystic and alveolar echinococcosis are severe zoonotic diseases characterized by long asymptomatic periods lasting months or years. Viable Echinococcus eggs released into the environment through the feces of canids can infect humans through accidental ingestion via hand-to-mouth contact or consumption of contaminated food or water. Both Echinococcus multilocularis and Echinococcus granulosus sensu lato are considered as foodborne parasites. However, when considering possible pathways of human infection, it appears that food and water-borne related variables do not significantly increase the risk of infection. Providing evidence-based data for the presence of DNA and, potentially, eggs in fresh produce is crucial in understanding foodborne transmission of Echinococcus spp. to humans. Two multicenter and multicountry studies were conducted within the One Health EJP framework to estimate the proportion of lettuces and berries contaminated by E. multilocularis, E. granulosus s.l., and other taeniid DNAs from 12 European countries, Tunisia and Pakistan. A total of 1,117 lettuces, 300 strawberries and 130 blueberries samples were collected and analyzed by washing, sequential sieving and real-time PCRs. Echinococcus multilocularis DNA was detected in 1.2% (7/570) of samples tested from the seven European endemic areas and in 2% (2/100) from Pakistan. In the five European endemic countries for E. granulosus s.l., E. granulosus sensu stricto DNA was identified in 1.3% of lettuces (9/695). The proportion of lettuces contaminated by E. granulosus sensu stricto DNA was 12% (9/75) in Tunisia and 4% (4/100) in Pakistan. Regarding berries, E. multilocularis DNA was detected in 5.4% of strawberries (n=11/202), 7.3% of blueberries (6/82) from the seven European endemic countries and 56% of blueberries (14/25) from Pakistan. High contamination rates of E. granulosus s.s were found outside of Europe, with 12.0% in blueberries (3/25) from Pakistan and 81.3%. DNA in strawberries (13/16) from Tunisia. The total contamination rate of all taeniid species DNA in lettuces (5.3%; 59/1,117) and berries (12.1%; 58/480) suggests that the transfer of taeniid eggs from carnivore feces to food is not uncommon. Although we assume that eggs are the source of the DNA detected in this study, the viability of such eggs is unknown. The detection of Echinococcus species in lettuces and berries suggests a potential risk of foodborne human infection. The relative contribution of this risk remains to be estimated. Further studies on food and environmental contamination are necessary to cover different epidemiological contexts and social habits, leading to a better understanding of human infections by Echinococcus eggs.

microbiology↗

bioRxiv2024

αKG-mediated carnitine synthesis promotes homologous recombination via histone acetylation

Homologous recombination (HR) deficiency enhances sensitivity to DNA damaging agents commonly used to treat cancer. In HR-proficient cancers, metabolic mechanisms driving response or resistance to DNA damaging agents remain unclear. Here we identified that depletion of alpha-ketoglutarate (KG) sensitizes HR-proficient cells to DNA damaging agents by metabolic regulation of histone acetylation. KG is required for the activity of KG-dependent dioxygenases (KGDDs), and prior work has shown that changes in KGDD affect demethylases. Using a targeted CRISPR knockout library consisting of 64 KGDDs, we discovered that Trimethyllysine Hydroxylase Epsilon (TMLHE), the first and rate-limiting enzyme in de novo carnitine synthesis, is necessary for proliferation of HR-proficient cells in the presence of DNA damaging agents. Unexpectedly, KG-mediated TMLHE-dependent carnitine synthesis was required for histone acetylation, while histone methylation was affected but dispensable. The increase in histone acetylation via KG-dependent carnitine synthesis promoted HR-mediated DNA repair through site- and substrate-specific histone acetylation. These data demonstrate for the first time that HR-proficiency is mediated through KG directly influencing histone acetylation via carnitine synthesis and provide a metabolic avenue to induce HR-deficiency and sensitivity to DNA damaging agents.

cancer biology↗

bioRxiv2023

Study on Spatio-temporal Prevalence and Hematological Attributes of Bovine Babesiosis in Cattle Population of Layyah, Southern Punjab, Pakistan

The objective of the present study was to investigate the spatiotemporal prevalence of bovine babesiosis in cattle population (n=376) of District Layyah, South Punjab, Pakistan as affected by location, age, breed, gender and seasons. Blood samples were collected aseptically and assessed for babesiosis through microscopy and PCR, and through automated analyzer for hematological attributes. Overall results of prevalence as attained through PCR in cattle population showed a significantly (P[≤]0.05) lower prevalence of 19.4% (n=72/376) as compared to 37.2% (n=140/276) through microscopy. None of the studied cattle from Cholistani breed were Babesia-positive. However, significantly (P[≤]0.05) higher prevalence was noticed for crossbred cattle (46.7%, n= 50/107) followed by that in Friesian (16.1%, n= 10/62), Jersey (7%, n= 5/71) and Sahiwal (6.9%, n= 7/101) cattle breeds. Female cattle (19.5%, n= 55/281) and age group 1 (Up to 2 years) (40%, n= 42/105) had higher prevalence of Babesia as ascertained through PCR in comparison to their counterpart groups. Significantly (P[≤]0.05) higher prevalence of 35.9% (n=60/167) was shown in summer as compared to that in winter season (5.7%, n= 12/209). All the positive samples produced the 490bp amplicons specific and typical for Babesia bigemina. Regarding hematology, hemoglobin concentration, erythrocytic count, hematocrit and mean corpuscular volume were significantly (P[≤]0.05) lower in babesia-positive cattle as compared to healthy ones. In a nutshell, indigenous cattle breeds are tick-resistant hardy breeds and do not show severe signs of babesiosis as compared to exotic and crossbred cattle. Furthermore, Southern Punjab area of Pakistan has a different spatiotemporal distribution of babesiosis with bigemina being predominant.

immunology↗

bioRxiv2022

Plasmid Permissiveness of Wastewater Microbiomes can be Predicted from 16S rDNA sequences by Machine Learning

Wastewater Treatment Plants (WWTPs) contain a diverse microbial community with high cell density. They constantly receive antimicrobial residues and resistant strains and, therefore, may offer conditions for the Horizontal Gene Transfer (HGT) of antimicrobial resistance determinants, transmitting clinically important genes between, e.g., enteric and environmental bacteria and vice versa. Despite the clinical importance, tools for predicting HGT are still under-developed. In this study, we examined to which extent microbial community composition, as inferred by partial 16S rRNA gene sequences, can predict plasmid permissiveness, i.e., the ability of cells to receive a plasmid through conjugation, for microbial communities in the water cycle, using data from standardized filter mating assays using fluorescent bio-reporter plasmids. We leveraged a range of machine learning models for predicting the permissiveness for each taxon in the community, translating to the range of hosts a plasmid is able to transfer to, for three broad host-range resistance plasmids (pKJK5, pB10, and RP4). Our results indicate that the predicted permissiveness from the best performing model (random forest) showed a moderate-to-strong average correlation of 0.45 for pB10 (95% CI: 0.42-0.52), 0.42 for pKJK5 (0.95% CI: 0.38-0.45) and 0.52 for RP4 (0.95% CI:0.45-0.55) with the experimental permissiveness in the unseen test dataset. Predictive phylogenetic signals occurred despite these being broad host-range plasmids. Our results provide a framework that contributes to assessing the risk of AMR pollution in wastewater systems. The predictive tool is available as a an application under https://github.com/DaneshMoradigaravand/PlasmidPerm.

bioinformatics↗

bioRxiv2021

Impact of pre-anthesis drought stress on physiology, yield-related traits and drought responsive genes in green super rice

Optimum soil water availability is vital for maximum yield production in rice which is challenged by increasing spells of drought. The reproductive stage drought is among the main limiting factors leading to the drastic reduction in grain yield. Objective of this study was to investigate the molecular and morpho-physiological responses of pre-anthesis stage drought stress in green super rice. The study assessed the performance of 26 rice lines under irrigated and drought conditions. Irrigated treatment was allowed to grow normally while drought stress was imposed for 30 days at pre-anthesis stage. Three important physiological traits including pollen fertility percentage (PFP), cell membrane stability (CMS) and normalized difference vegetative index (NDVI) were recorded at anthesis stage during the last week of drought stress. Agronomic traits of economic importance including grain yield were recorded at maturity stage. The analysis of variance demonstrated significant variation among the genotypes for most of the studied traits. Correlation and principal component analyses demonstrated highly significant associations of particular agronomic traits with grain yield, and genetic diversity among genotypes, respectively. Our study demonstrated a higher drought tolerance potential of GSR lines compared to local cultivars, mainly by higher pollen viability, plant biomass, CMS, and harvest index under drought. In addition, the molecular basis of drought tolerance in GSR lines was related to upregulation of certain drought responsive genes including OsSADRI, OsDSM1, and OsDT11. Our study identified novel drought tolerance related genes (OsDRG-1, OsDRG-2, OsDRG-3 and OsDRG-4) that could be further characterized using reverse genetics to be utilized in molecular breeding for drought tolerance.

plant biology↗

bioRxiv2021

Interplay between BALL and CBP maintains H3K27 acetylation on active genes in Drosophila

CREB binding protein (CBP) is a multifunctional transcriptional co-activator that interacts with a variety of transcription factors and acts as a histone acetyltransferase. In Drosophila, CBP mediated acetylation of histone H3 lysine 27 (H3K27ac) is a known hallmark of gene activation regulated by trithorax group proteins (trxG). Recently, we have shown that a histone kinase Ballchen (BALL) substantially co-localizes with H3K27ac at trxG target loci and is required to maintain gene activation in Drosophila. Here, we report direct interaction between BALL and CBP, which positively regulates H3K27ac. Analysis of genome-wide binding profile of BALL and CBP reveals major overlap and their co-localization at actively transcribed genes. We show that BALL biochemically interacts with CBP and depletion of BALL results in drastic reduction in H3K27ac. Together, these results demonstrate a previously unknown synergy between BALL and CBP and reveals a potentially new pathway required to maintain gene activation during development.

genomics↗

bioRxiv2020

Infrared Spectral Markers for the Nephroprotective Effects of Ficus deltoidea in Streptozotocin-induced Diabetic Rats

Fourier Transform Infrared (FTIR) is an established analytical technique to elucidate new discriminatory biomarkers. Our previous study showed that Ficus deltoidea (Ficus: Moraceae) is capable of increasing insulin secretion and improving tissue regeneration by reducing oxidative stress in diabetic rats. However, the assessment of treatment response is limited by the paucity of biomarkers. We aimed to evaluate the potential use of FTIR for assessing the nephroprotective effects of Ficus deltoidea (Ficus: Moraceae) in diabetic rats. A rat model of diabetes was induced using a single intraperitoneal injection of streptozotocin (STZ) (60 mg/kg body weight). Methanolic extract of F. deltoidea was administered orally at a dose of 1000 mg/kg body weight for eight weeks. Fasting blood glucose, serum insulin and kidney function parameters were examined. The kidneys were subsequently subjected to FTIR and histological analyses. Enzyme-linked immunosorbent assays (ELISA) assessed the levels of oxidative stress, antioxidant, and apoptosis-related proteins in the kidney tissue. The results show, for the first time, that there is a good agreement between changes in kidney and FTIR peaks. The IR peaks (1545 cm-1 and 1511 cm-1) corresponding to amide II were restored by treatment with F. deltoidea. Multivariate analysis demonstrated that the diabetic rats treated with F. deltoidea had similar clustering pattern that of the normal animals. Biochemical and histological examination further confirmed the nephroprotective effect of F. deltoidea. Thus, demonstrating how FTIR spectroscopy could be used for the diagnosis of diabetes kidney disease.

physiology↗

bioRxiv2020

Implications of the COVID-19 lockdown on dengue transmission and the occurrence of Aedes aegypti (Linnaeus) and Aedes albopictus (Skuse) in Malaysia

The impact of movement restrictions during the COVID-19 lockdown on the existing endemic infectious disease dengue fever has generated considerable research interest. We compared the Malaysia weekly epidemiological records of dengue incidences during the period of lockdown to the trend of previous years (2015 to 2019) and a simulation at the corresponding period that expected no movement restrictions. We found that the dengue incidence declined significantly with a greater magnitude at phase 1 of lockdown, with a negative gradient of 3.2-fold steeper than the trend observed in previous years and 6.5-fold steeper than the simulation, indicating that the control of population movement did reduce dengue transmission. However, starting from phase 2 of lockdown, the dengue incidences demonstrated an elevation and earlier rebound by at least 4 weeks and grew with an exponential pattern compared to the simulation and previous years. Together with our data on Aedes mosquitoes from a district of Penang, Malaysia, we revealed that Aedes albopictus is the predominant species for both indoor and outdoor environments. The abundance of the mosquito was increasing steadily during the period of lockdown, and demonstrated strong correlation with the locally reported dengue incidences; therefore, we proposed the possible diffusive effect of vector that led to a higher acceleration of incidence rate. These findings would help authorities review the direction and efforts of the vector control strategy.

zoology↗

bioRxiv2020

Agro-morphological, yield, and genotyping-by-sequencing data of selected wheat germplasm

Wheat (Triticum aestivum) is the most important staple food in Pakistan. Knowledge of its genetic diversity is critical for designing effective crop breeding programs. Here we report agro-morphological and yield data for 112 genotypes (including 7 duplicates) of wheat (Triticum aestivum) cultivars, advance lines, landraces and wild relatives, collected from several research institutes and breeders across Pakistan. We also report genotyping-by-sequencing (GBS) data for a selected sub-set of 52 genotypes. Sequencing was performed using Illumina HiSeq 2500 platform using the PE150 run. Data generated per sample ranged from 1.01 to 2.5 Gb; 90% of the short reads exhibited quality scores above 99.9%. TGACv1 wheat genome was used as a reference to map short reads from individual genotypes and to filter single nucleotide polymorphic loci (SNPs). On average, 364,074{+/-}54479 SNPs per genotype were recorded. The sequencing data has been submitted to the SRA database of NCBI (accession number SRP179096). The agro-morphological and yield data, along with the sequence data and SNPs will be invaluable resources for wheat breeding programs in future.

genetics↗

bioRxiv2019

The effect of single-task training on learning transfer to a novel bimanual task

BackgroundThe contextual interference effect suggests that the random practice of multiple-tasks is more beneficial for the retention and transfer of the learning as compared to blocked practice. Therefore, the transfer of learning is usually attributed to the contextual interference effect and is studied in a multi-task setting. ObjectiveThe goals of this study were to evaluate whether the transfer of learning (i) can occur when a single bimanual task is practiced, (ii) is affected by the knowledge of results (feedback), and (iii) sustains over an extended number of trials. MethodsFifty-two healthy subjects were equally divided into four groups. Before the transfer test, two groups practiced a bimanual finger-tapping task with feedback (EF) and without feedback (ENF). The third group (IM) practiced the same task using the kinesthetic motor imagery, whereas the last group acted as a control (CTRL) and performed only a bimanual button-pressing task used for the transfer test. ResultsLinear mixed-model showed that in the transfer test, groups EF, ENF and IM had similar performance but significantly higher scores compared to the CTRL group. Compared to the CTRL, the EF and IM groups showed significantly improved performance in most of the sessions but group ENF had similar results. ConclusionThis study suggests that the single-task practice of a discrete bimanual task can facilitate the learning transfer to a novel task and knowledge of results (feedback) have no significant impact on the transfer of learning. Moreover, the transfer of learning effect does not disappear in extended trials. HighlightsO_LISingle-task practice of a discrete bimanual task can facilitate the learning of a novel bimanual task C_LIO_LIKnowledge of results (feedback) does not improve learning transfer in single-task setting C_LIO_LITransfer of learning effect does not disappear in extended trials C_LI

neuroscience↗

bioRxiv2019

Diet composition of introduced Barn Owls (Tyto alba javanica) in urban area in comparison with agriculture settings

This study investigated the diet of introduced barn owls (Tyto alba javanica, Gmelin) in the urban area of the Main Campus of Universiti Sains Malaysia, Penang, Malaysia, based on collected regurgitated pellets. We also compared the diet of introduced urban barn owls with the diet of barn owls from two agricultural areas, i.e. oil palm plantations and rice fields. Pellet analysis of barn owls introduced in the urban area showed that commensal Norway rats, Rattus norvegicus, made up the highest proportion of the diet (65.37% prey biomass) while common shrews, Suncus murinus were the second highest consumed prey (30.12% prey biomass). Common plantain squirrel, Callosciurus notatus, made up 4.45% of the diet while insects were taken in a relatively small amount (0.046% prey biomass). Introduced barn owls showed a preference for medium-sized prey, i.e. 40 to 120g (52.96% biomass and 38.71% total). In agricultural areas, Rattus argentiventer predominated the diet of barn owls (98.24% prey biomass) in rice fields while Malayan wood rats, Rattus tiomanicus, were the most consumed prey in oil palm plantations (99.5% prey biomass). Food niche breadth value was highest for barn owls introduced in an urban area with a value of 2.90, and 1.06 in rice fields and 1.22 in oil palm plantations. Our analysis reiterates the prey preference of barn owls in various landscapes for small mammals. Our results also indicate the suitability of utilizing barn owls as a biological control not only in agricultural areas, but also as a biological control agent for commensal rodent pests in urban areas.

ecology↗