Biology subjects

Afzal, T.

Publications and source records attributed to Afzal, T..

4 recordsLinked to original sources

bioRxiv2026

Comparison of Galleria mellonella, Epithelial Cell Cytotoxicity, and Mouse Model of Bacteremia to Measure Pseudomonas aeruginosa Virulence

Considerable effort has focused on identifying alternatives to mouse models in research studies. In the field of bacterial pathogenesis, Galleria mellonella and epithelial cell lines have been widely used for this purpose, but the concordance of these models with mice remains unclear. To begin to address this knowledge gap, we used 105 clinical isolates of Pseudomonas aeruginosa for which the virulence had been previously determined in a mouse bacteremia model. A semistrong correlation was observed between G. mellonella median time to 50% mortality and mouse 50% pre-lethal dose (LD50) values (Spearmans rank correlation coefficient [{rho}] = 0.75), whereas percent A549 epithelial-like cell lysis during co-culture showed a weak correlation to mouse LD50 values ({rho} = -0.47). Given the stronger correlation between G. mellonella and mouse virulence, we next examined whether G. mellonella could substitute for mice when asking questions about the virulence of large numbers of P. aeruginosa isolates. Results from mice indicated that isolates with resistance to more antibiotics were significantly less virulent, and the use of G. mellonella identified the same inverse correlation. Furthermore, both models found no evidence for the existence of hypervirulent clonal lineages. In particular, isolates belonging to sequence types defined as high-risk clones were not consistently more virulent than other isolates, despite the known association of high-risk clones with poor clinical outcomes. These findings suggest that G. mellonella can serve as an adequate substitute for mice when addressing specific population-based virulence questions, although conclusions should be confirmed in mice. Author SummaryWe found that virulence measurements in a G. mellonella infection model showed a semistrong correlation with those from a mouse bacteremia model and that this insect larval model adequately detected population-level trends similarly to mice. In contrast, A549 epithelial-like cell lysis during bacterial co-culture correlated less well with mouse virulence. Together, these results support the use of G. mellonella as a scalable, low-cost, and humane first-line model for assessing P. aeruginosa virulence but also indicate that conclusions should be validated in mice.

microbiology↗

bioRxiv2026

Virtual Immersion in Biomedical Engineering (VIBE): Exposing undergraduates to culturally sensitive engineering design and professional experiences at scale

ChallengeUndergraduate engineering students often face two major barriers: limited access to culturally sensitive global experiences and difficulty securing design internship opportunities. Traditional study abroad and internship programs can be inaccessible due to financial, geographic, or structural constraints, hindering the development of global competencies and practical engineering skills. Novel InitiativeTo address these gaps, we created the Virtual Immersion in Biomedical Engineering (VIBE) program, a free, inclusive, and scalable summer experience. The 8-week online program blends interactive sessions on the engineering design process (EDP), faculty led research talks, and professional development workshops. Collaborative team-based design challenges focused on global health and healthcare disparities are completed by international teams of 3-4 students. From 2021 to 2024, more than 800 students from over 20 countries participated, with an even balance of male and female students. Student presentations (four-minute videos uploaded to YouTube) were evaluated using rubrics with the aid of a large language model. The assessment revealed substantial learning of the EDP, especially in problem definition and communication. ReflectionParticipant feedback underscored the programs benefits: exposure to global collaboration, professional development, and flexibility. However, common challenges included time zone coordination and team dynamics. Despite these hurdles, VIBE has demonstrated that virtual experiential learning can effectively build engineering design skills and global awareness. It offers a promising, accessible alternative to traditional high-cost global programs, expanding equitable opportunities for engineering students worldwide.

bioengineering↗

bioRxiv2025

Atorvastatin suppresses cardiac fibrosis and dysfunction induced by HIV and certain antiretroviral drugs in mice by blocking platelet TGFβ1

Cardiovascular disease (CVD) both atherosclerosis-related and heart failure with preserved ejection fraction (HFpEF) and linked to cardiac fibrosis, contributes to morbidity and mortality in people with HIV (PWH) receiving antiretroviral therapy (ART). In the REPRIEVE trial, pitavastatin reduced atherosclerotic CVD risk to a magnitude inconsistent with pitavastatins impact solely on LDL-cholesterol and inflammation. We hypothesized that HFpEF in PWH relates to HIV-induced fibrosis mediated by platelet TGF{beta}1, that it is accelerated by certain contemporary ART, and may also be inhibited by statins. ART drugs used in REPRIEVE, including a nucleoside/nucleotide, integrase inhibitor-based regimen (tenofovir (TDF), emtricitabine (FTC), and dolutegravir (DTG)), and the protease inhibitors ritonavir (RTV) and darunavir (DRV), and the impact of atorvastatin, were examined in two HIV mouse models: transgenic Tg26 mice and HIV-PDX mice engrafted with HIV-infected T cells. Tg26 and HIV-PDX mice had higher cardiac fibrosis than littermate controls without HIV (p<0.05). Administration of TDF-FTC-DTG or RTV, but not DRV, resulted in a further [~]2-fold increase in fibrosis (p<0.01). Higher cardiac fibrosis with intracardiac fat accumulation correlated with reduced diastolic function. Mice depleted of platelet TGF{beta}1 (TGF{beta}1Platelet-{Delta}Tg26), or treated with atorvastatin, were partially protected from HIV- and ART-induced cardiac fibrosis, steatosis, and diastolic dysfunction. Atorvastatin effects occurred independently of changes in inflammatory cytokines and total cholesterol. They correlated with reduced platelet activation and TGF{beta}1 signaling in cardiac endothelial cells, fibroblasts, and macrophages undergoing mesenchymal transition. These results indicate that certain ART regimens accelerate HIV-associated CVD characterized by HFpEF via platelet TGF{beta}1-dependent processes and mitigated by atorvastatin. They enhance understanding of the pleiotropic effects of statins in HIV/ART CVD and suggest a mechanism that might be targeted by antiplatelet agents or inhibition of TGF{beta} signaling. Key PointsO_LIContemporary ART regimens induce release of platelet TGF{beta}1 and are associated with cardiac fibrosis and diastolic dysfunction with ectopic fat deposition in HIV-infected mice. C_LIO_LIDepleting platelet TGF{beta}1 and/or treating with atorvastatin therapy suppresses HIV-ART-induced cardiac fibrosis, suggesting use of anti-platelet strategies to prevent heart failure among PWH. C_LI

biochemistry↗

bioRxiv2021

Genomic and phenotypic characterization of Pseudomonas hygromyciniae, a novel bacterial species discovered from a commercially purchased antibiotic

A purchased lot of the antibiotic hygromycin B was found to be contaminated with a novel bacterial species, which we designate Pseudomonas hygromyciniae. Characteristics of P. hygromyciniae include its ability to use a variety of compounds as carbon sources, its pathogenicity towards lettuce and Galleria mellonella, and its ability to inhibit the growth of an E. coli strain. P. hygromyciniae is unlikely to be a human pathogen, as it did not survive at 37 {degrees}C and was not cytotoxic towards a mammalian cell line. The P. hygromyciniae strain harbors a novel 250 kb megaplasmid which confers resistance to hygromycin B and contains numerous other genes predicted to encode replication and conjugation machinery. These findings indicate that commercially manufactured antibiotics represent another extreme environment that may support the growth of novel bacterial species. IMPORTANCEMicrobial ecologists have surveyed numerous natural and manmade environments in search of new microbial species. In some instances, these microbes are discovered in harsh conditions, such as deep-sea vents, and their discovery leads to better understanding of how microbes adapt to their environment. Here, we have discovered a new species of bacteria from an extreme manmade environment: a lyophilized, commercially available bottle of the antibiotic hygromycin B.

microbiology↗