Biology subjects

Shamsuzzaman, S.

Publications and source records attributed to Shamsuzzaman, S..

3 recordsLinked to original sources

bioRxiv2026

Comparative immunogenicity and protective efficacy of formaldehyde-inactivated whole-cell and sonicated whole-cell extract vaccines against multidrug-resistant Pseudomonas aeruginosa in mice

Background: Pseudomonas aeruginosa is a major opportunistic Gram-negative pathogen responsible for healthcare-associated infections, while increasing antimicrobial resistance has narrowed therapeutic options. Vaccine development therefore represents an important complementary strategy for prevention. This study compared the immunogenicity and protective efficacy of a formaldehyde-inactivated whole-cell vaccine with a sonicated whole cell extract preparation against multidrug-resistant (MDR) P. aeruginosa in mouse model. Methods: Clinical P. aeruginosa isolates were obtained from specimens collected at Dhaka Medical College Hospital between July 2022 and February 2026. Formaldehyde-inactivated whole-cell and sonicated whole cell extract preparations were produced from P. aeruginosa. A total of 144 female Swiss albino mice aged 6-8 weeks were used: 120 mice were allocated to two independent immunization experiments and 24 mice were used for LD50 determination. Mice received three intramuscular immunizations on days 0, 14, and 28. Antigen-specific serum IgG was assessed by enzyme-linked immunosorbent assay (ELISA), functional antibody activity was evaluated by serum bactericidal assay (SBA), and protective efficacy was assessed following lethal intraperitoneal challenge. Results: Ten isolates from MDR P. aeruginosa were selected by simple random sampling from the clinical isolates for vaccine preparation. The estimated protein concentration of the sonicated preparation was 1.872 mg/mL. Both vaccine groups developed significantly higher anti-P. aeruginosa IgG responses than the control group after immunization (p<0.001). Following lethal challenge, survival was 100% in mice receiving the formaldehyde-inactivated vaccine and 91.7% among mice receiving the sonicated preparation; no control mice survived. Between-vaccine differences in survival were not statistically significant. SBA demonstrated complement-dependent bactericidal activity in sera from both vaccinated groups, with activity detectable to a dilution of 1:32 for the whole-cell vaccine and 1:64 for the sonicated preparation. Conclusions: Both vaccine preparations elicited strong humoral responses and substantial protection against lethal MDR P. aeruginosa challenge in mice. The findings support further investigation of multicomponent P. aeruginosa vaccine strategies, although additional studies using multiple challenge strains and broader immunological endpoints are required before conclusions regarding translational efficacy can be drawn.

microbiology↗

bioRxiv2026

Dietary depletion of glutamine is atheroprotective

Heart attacks and strokes are late-stage complications of rupture of unstable atherosclerotic plaques. Stable plaques contain stabilizing matrix-producing fibrotic cells, largely smooth muscle cell (SMC)-derived. The molecular drivers of SMC phenotypic transitions to beneficial fibrotic or destabilizing inflammatory and calcifying phenotypes are unclear. Since atherosclerosis develops over decades, there is extensive interest in identifying dietary alterations that enhance plaque stability. We demonstrate that SMC acquire a fibrotic phenotype dependent on glutamine-derived metabolites supporting both catabolism and collagen synthesis. Moreover, dietary glutamine restriction decreases mortality of mice susceptible to atherosclerotic plaque rupture. Lesions from glutamine-restricted mice are smaller and have increased SMC investment. This study identifies dietary glutamine as a driver of cardiovascular mortality, suggesting a new strategy for reducing late-stage complications of atherosclerosis.

physiology↗

bioRxiv2023

Mouse Model of Heart Attack and Stroke Shows Improved Survival with MPO Inhibition

Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of death worldwide1. Unfortunately, the lack of a mouse model that develops advanced coronary atherosclerosis and that exhibits a high incidence of spontaneous plaque rupture with MI or stroke has greatly stymied development of more effective therapeutic approaches for reducing these events beyond what has been achieved with aggressive lipid lowering. Herein, we describe a novel mouse model that develops widespread advanced atherosclerosis including in coronary, brachiocephalic, and carotid arteries. These mice show high mortality following Western Diet feeding with clear evidence of plaque rupture, MI, and stroke. To validate the utility of this model, mice were treated with the drug candidate AZM198, which inhibits myeloperoxidase, an enzyme primarily produced by activated neutrophils and predictive of rupture of human atherosclerotic lesions2-7. AZM198 treatment resulted in marked improvements in survival with a greater than 60% decrease in the incidence of plaque rupture, MI, and stroke. In summary, our work describes a novel mouse model that closely replicates late-stage clinical events of advanced human atherosclerotic disease and evidence that this model can be used to identify and test potential new therapeutic agents to prevent major adverse cardiac events.

physiology↗