Biology subjects

Sharp, M. E.

Publications and source records attributed to Sharp, M. E..

2 recordsLinked to original sources

bioRxiv2025

RodA Promotes Intestinal Colonization by Group B Streptococcus

BackgroundGroup B Streptococcus (GBS) intestinal colonization is critical for the pathogenesis of late-onset (LO) disease in infants. Using a murine model, we explore the role of rodA, which encodes a peptidoglycan polymerase RodA, belonging to the Shape, Elongation, Division, and Sporulation (SEDS) family that participates in peptidoglycan synthesis and maintenance of cell wall integrity. MethodsWe investigated the contribution of rodA to GBS gastrointestinal (GI) colonization using a wild-type strain (A909 WT) and an isogenic in-frame deletion mutant of rodA (A909{Delta}rodA). Morphological differences between the two strains were examined by transmission electron microscopy (TEM), and the contribution of rodA to GI colonization was assessed in a murine model through monocolonization and cocolonization experiments. We evaluated the growth of the mutant strain under intestinal physiological stress conditions and characterized its interactions with host epithelial cells in vitro. ResultsA909{Delta}rodA showed a unique chaining/aggregation phenotype compared to the A909 WT strain, with the presence of capsule confirmed via TEM and immunoblotting. In murine cocolonization experiments, A909 WT outcompeted A909{Delta}rodA; however, monocolonization experiments exhibited comparable colonization and bacterial burden across the GI tract. In vitro experiments revealed impaired growth in bile and an increase in adhesion to intestinal epithelial cells by the {Delta}rodA mutant. Conclusion(s)rodA plays a role in GBS intestinal colonization. Deletion of rodA increases sensitivity to gastrointestinal stressors in vitro and causes a pronounced defect in competition in vivo, suggesting that the presence of rodA increases the fitness of GBS in the gut.

microbiology↗

bioRxiv2019

Dopamine modulates learning-related changes in dynamic striatal-cortical connectivity in Parkinson’s disease

Learning from reinforcement is thought to depend on striatal dopamine inputs, which serve to update the value of actions by modifying connections in widespread cortico-striatal circuits. While considerable research has described the activity of individual striatal and midbrain regions in reinforcement learning, the broader role for dopamine in modulating network-level processes has been difficult to decipher. To examine whether dopamine modulates circuit-level dynamic connectivity during learning, we characterized the effects of dopamine on learning-related dynamic functional connectivity estimated from fMRI data acquired in patients with Parkinsons disease. Patients with Parkinsons disease have severe dopamine depletion in the striatum and are treated with dopamine replacement drugs, providing an opportunity to compare learning and network dynamics when patients are in a low dopamine state (off drugs) versus a high dopamine state (on drugs). We assessed the relationship between dopamine and dynamic connectivity while patients performed a probabilistic reversal learning task. We found that reversal learning altered dynamic network flexibility in the striatum and that this effect was dependent on dopaminergic state. We also found that dopamine modulated changes in connectivity between the striatum and specific task-relevant visual areas of inferior temporal cortex, providing empirical support for theories stipulating that value is updated through changes in cortico-striatal circuits. These results suggest that dopamine exerts a widespread effect on neural circuitry and network dynamics during reinforcement learning.

neuroscience↗