Biology subjects

Yaqub, M.

Publications and source records attributed to Yaqub, M..

7 recordsLinked to original sources

bioRxiv2026

Polystyrene Microplastics Accelerate Antibiotic Resistance Evolution and Exacerbate Pathogenicity in Acinetobacter Baumannii

Microplastics are pervasive environmental contaminants and are increasingly detected in contexts relevant to human health, yet their effects on antimicrobial resistance, host-pathogen interactions, and infection outcomes remain poorly understood. Here, we show that exposure to polystyrene microplastics alters both antibiotic resistance evolution and pathogenic behavior in Acinetobacter baumannii, a leading cause of multidrug-resistant hospital-acquired infections. Using experimental evolution under antibiotic selection, we demonstrate that microplastic exposure accelerates resistance emergence across multiple antibiotic classes. Although microplastic exposure did not uniformly enhance biofilm formation, it modestly impaired macrophage-mediated bacterial clearance, suggesting broader effects on bacterial adaptation and host interaction. In vivo, microplastic-associated infection resulted in more severe disease, characterized by increased lung tissue damage and reduced survival in a murine model of A. baumannii pneumonia. Together, these findings identify microplastics as ecological modifiers of bacterial adaptation, linking widespread plastic pollution to enhanced antimicrobial resistance and worsened infectious disease outcomes.

microbiology↗

bioRxiv2026

DISRUPTION OF A DNA REPAIR PROTEIN PROMOTES ANTIBIOTIC RESISTANCE IN ACINETOBACTER BAUMANNII

Acinetobacter baumannii is a high priority Gram negative opportunistic pathogen known for its high rates of multidrug resistance (MDR). Minocycline (MIN), a tetracycline class antibiotic, is one of the most effective antibiotics for treating A. baumannii infections in patients. Unfortunately, MIN resistance is spreading internationally and has begun to emerge in the United States. While efflux pumps are correlated with MIN resistant A. baumannii, clinical data suggests alternative mechanisms of MIN resistance. To explore the genetic basis for MIN resistance in A. baumannii we employed a machine learning model to predict genetic resistance correlates from clinical isolates. Mutations in ruvB, a DNA repair protein, were strongly correlated with MIN resistant clinical strains of A. baumannii .Consistent with the prediction, tn26 insertion in ruvB in A. baumannii strain AB5075, and deletion of ruvB in strain ATCC 19606, increased MIN minimum inhibitory concentrations to a level that exceeds the MIN resistance breakpoint. RuvB complexes with RuvA and RuvC to resolve Holliday junctions during recombination. However, only ruvB mutants showed the resistance phenotype; neither ruvA nor ruvC mutants were MIN resistant, suggesting loss of the activity of the complex was not the basis for resistance. We observed ruvB mutants produced increased biomass during planktonic growth relative to the other two ruv mutants. Upon examination, the ruvB::tn26 mutant had a 451% increase in biomass and 360% thicker biofilms relative to wildtype. We determined the disruption of ruvB lead to thicker biofilms and enriched in extracellular DNA (eDNA), and DNase I treatment collapsed the enhanced biofilm phenotype and markedly reduced tetracycline class MICs. FLAG-RuvA accumulated within the biofilm matrix in the absence of RuvB, supporting a model in which RuvA contributes to stabilization of eDNA-rich structures. In a murine pneumonia model, ruvB disruption did not significantly alter survival or pulmonary burden in untreated infection but reduced bacterial dissemination and increased minocycline resistance. Together, these findings reveal an unexpected connection between Holliday junction processing, eDNA-rich biofilm architecture, and antibiotic resistance in A. baumannii.

microbiology↗

bioRxiv2026

A Clinically Silent Resistance Phenotype That Promotes Acinetobacter baumannii Survival During Colistin Therapy

Acinetobacter baumannii is a major cause of multidrug-resistant nosocomial infections, particularly ventilator-associated pneumonia, for which therapeutic options are increasingly limited. Colistin, a polymyxin antibiotic, is a drug of last resort for A. baumannii, boasting high susceptibility rates. Yet, despite relatively low rates of breakpoint-defined colistin resistance, clinical outcomes are highly variable, and the bacterial strategies that enable survival during colistin therapy remain poorly understood. Here, we integrate supervised machine-learning-guided genomic prioritization with functional, physiological, and in vivo analyses to interrogate the genetic basis of colistin response in A. baumannii. Machine-learning analysis of clinical isolates identified candidate loci associated with colistin survival, many of which did not alter minimum inhibitory concentration (MIC) when disrupted. Instead, growth-dynamic assays uncovered a subset of mutants capable of maintaining fitness upon inhibitory colistin exposure despite classification as susceptible via standardized antibiotic susceptibility testing. We define this phenotype as clinically silent resistance (CSR), a genetically encoded, MIC-independent survival state. Using a murine pneumonia model, we further demonstrate that CSR mutants thrive during colistin therapy in vivo. Together, these findings reveal a hidden layer of colistin survival that is not captured by standard susceptibility testing and highlight fundamental limitations of breakpoint-centric paradigms for predicting treatment outcomes in A. baumannii.

microbiology↗

bioRxiv2024

Biosynthesis of mitis group streptococcal glycolipids and their roles in physiology and antibiotic susceptibility

Bacterial cell surface components such as lipoteichoic acids (LTAs) play critical roles in host-microbe interactions and alter host responses based on their chemical structures. Mitis group streptococci have commensal and pathogenic interactions with the human host and produce Type IV LTAs that are slightly different in chemical structures between species. To reveal the molecular bases for the intricate interactions between MGS and human hosts, a detailed understanding of the structure and biosynthetic process of MGS LTAs is needed. In this study, we used genomic and lipidomic techniques to elucidate the biosynthetic processes of Type IV LTA and its associated glycolipid anchors, monohexosyl-diacylglycerol and dihexosyl-diacyglycerol, in the infectious endocarditis isolate Streptococcus sp. strain 1643. Through establishing a murine sepsis model, we validated the essentiality of these glycolipids in the full virulence of S. mitis. Additionally, we found that these glycolipids play an important role in protecting the bacteria from antimicrobials. Overall, results obtained through this study both confirm and dispute aspects of the existing model of glycolipids biosynthesis, provide insights into the fundamental roles of bacterial glycolipids, as well as suggest the potential of targeting glycolipids for developing antimicrobial therapeutics. Significance/ImportanceGlycolipids and glycolipid-anchored LTAs are common and essential membrane components in Gram-positive bacteria. Yet, the biosynthesis and functions of LTAs have not been fully understood for many significant Gram-positive pathogens. Through genomic, lipidomic, and animal infection model analyses, as well as antimicrobial susceptibility assays, this study advances our understanding of Type IV LTA biosynthesis and the physiological roles of glycolipids in mitis group streptococci. Overall, our work establishes the essentiality of glycolipids in both bacterial virulence and defense against antimicrobials.

microbiology↗

bioRxiv2024

Antimicrobial Activity of Clove Extracts against Microorganisms Isolated from Vaginal Discharge

Infections of the genitourinary and reproductive tracts pose significant health concerns for women, particularly those of reproductive age. These infections often manifest as vaginal discharge and can be caused by a variety of microorganisms, including pathogenic bacteria and fungi. Traditional antibiotic treatments are increasingly challenged by the rise of antibiotic-resistant strains, underscoring the need for alternative therapies. This study aimed to isolate and identify microorganisms from vaginal swab samples and evaluate the antimicrobial efficacy of clove (Eugenia caryophyllata) extracts against these isolates. Using CLED agar, nutrient agar, and Sabouraud dextrose agar, a diverse range of bacterial and fungal flora were isolated from eight vaginal swab samples. The primary bacterial isolates included Proteus mirabilis, Escherichia coli, Staphylococcus aureus, and Lactobacillus spp., while Candida albicans was the main fungal isolate. Biochemical tests confirmed the identity of these microorganisms. The study found that ethanol clove extract exhibited significant antimicrobial activity, particularly against Staphylococcus aureus and Candida albicans, with the minimum inhibitory concentration (MIC) values being 20 mg/ml and 10 mg/ml, respectively. Additionally, ciprofloxacin, used as a control antibiotic, showed maximum inhibition against Lactobacillus spp., highlighting a potential risk for disrupting beneficial vaginal flora when using conventional antibiotics. The findings suggest that ethanol clove extract could serve as an effective alternative antimicrobial agent, reducing the risk of antibiotic resistance and preserving the balance of the vaginal microbiome. This research emphasizes the importance of exploring plant-based antimicrobial agents as viable alternatives to traditional antibiotics. The significant antimicrobial properties of clove extract against common vaginal pathogens offer promising implications for future therapeutic applications in managing vaginal infections.

microbiology↗

bioRxiv2021

PET-BIDS, an extension to the brain imaging data structure for positron emission tomography

The Brain Imaging Data Structure (BIDS) is a standard for organizing and describing neuroimaging datasets. It serves not only to facilitate the process of data sharing and aggregation, but also to simplify the application and development of new methods and software for working with neuroimaging data. Here, we present an extension of BIDS to include positron emission tomography (PET) data (PET-BIDS). We describe the PET-BIDS standard in detail and share several open-access datasets curated following PET-BIDS. Additionally, we highlight several tools which are already available for converting, validating and analyzing PET-BIDS datasets.

neuroscience↗

bioRxiv2020

DNA methylation classification in diffuse glioma shows little spatial heterogeneity after adjusting for tumor purity

Intratumoral heterogeneity is a hallmark of diffuse gliomas. We used neuronavigation to acquire 133 image-guided and spatially-separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma, which we characterized using DNA methylation arrays. Samples were obtained from regions with and without imaging abnormalities. Methylation profiles were analyzed to devise a three-dimensional reconstruction of genetic and epigenetic heterogeneity. Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and largely explains apparent epigenetic spatial heterogeneity. Indeed, we observed that DNA methylation subtypes are highly conserved in space after adjusting for tumor purity. Genome-wide heterogeneity analysis showed equal or increased heterogeneity among normal tissue when compared to tumor. These findings were validated in a separate cohort of 61 multi-sector tumor and 64 normal samples. Our findings underscore the infiltrative nature of diffuse gliomas and suggest that heterogeneity in DNA methylation is innate to somatic cells and not a characteristic feature of this tumor type.

cancer biology↗