Biology subjects

Bhawal, R.

Publications and source records attributed to Bhawal, R..

3 recordsLinked to original sources

bioRxiv2025

Harmful algal bloom species Microcystis aeruginosa releases thiamin antivitamins to suppress competitors

In environmental ecosystems, vitamin concentrations are often exceedingly low (1, 2) and auxotrophy, or reliance on exogenous vitamin or vitamin precursors, is widespread (3-5). We show here that the widespread harmful algal bloom (HAB) species Microcystis aeruginosa, threatening freshwater aquatic ecosystems globally, releases a complex mixture of thiamin antivitamins, including bacimethrin and methoxythiamin, which induce thiamin deficiency in the benign model green alga Chlamydomonas reinhardtii. Putative biosynthetic genes for bacimethrin were upregulated in M. aeruginosa when grown in co-culture resulting in greater production of bacimethrin. Bacimethrin, methoxythiamin, oxidized forms of thiamin and methoxythiamin, and a novel structural homolog of bacimethrin were all found at elevated levels in the co-culture exometabolome extracts and were all inhibitory to the growth of C. reinhardtii individually at very low concentrations and as a mixture in culture medium extracts. The thiamin-requiring mutant C. reinhardtii, CC-25, was much more sensitive to bacimethrin and methoxythiamin than the wildtype. Thiamin addition largely rescued the inhibitory effects of exposure to antivitamins in both the wildtype and mutant strain. Finally, we determined that bacimethrin is present in aquatic environments and is elevated during Microcystis blooms. Thus, allelopathic suppression of competitors, particularly those that are auxotrophic for thiamin, by M. aeruginosa via the production of antivitamins in environments where thiamin availability is low, could help this species to become dominant and form blooms.

microbiology↗

bioRxiv2023

Post-ischemic ubiquitination at the postsynaptic density reversibly influences the activity of ischemia-relevant kinases

Ubiquitin modifications alter protein function and stability, thereby regulating cell homeostasis and viability, particularly under stress. Ischemic stroke induces protein ubiquitination at the ischemic periphery, wherein cells remain viable, however the identity of ubiquitinated proteins is unknown. Here, we employed a proteomics approach to identify these proteins in mice undergoing ischemic stroke. The data are available in a searchable web interface (https://hochrainerlab.shinyapps.io/StrokeUbiOmics/). We detected increased ubiquitination of 198 proteins, many of which localize to the postsynaptic density (PSD) of glutamatergic neurons. Among these were proteins essential for maintaining PSD architecture, such as PSD95, as well as NMDA and AMPA receptor subunits. The largest enzymatic group at the PSD with elevated post-ischemic ubiquitination were kinases, such as CaMKII, PKC, Cdk5, and Pyk2, whose aberrant activities are well-known to contribute to post-ischemic neuronal death. Concurrent phospho-proteomics revealed altered PSD-associated phosphorylation patterns, indicative of modified kinase activities following stroke. PSD-located CaMKII, PKC, and Cdk5 activities were decreased while Pyk2 activity was increased after stroke. Removal of ubiquitin restored kinase activities to pre-stroke levels, identifying ubiquitination as the responsible molecular mechanism for post-ischemic kinase regulation. These findings unveil a previously unrecognized role of ubiquitination in the regulation of essential kinases involved in ischemic injury.

neuroscience↗

bioRxiv2019

Succinylation Links Metabolic Reductions to Amyloid and Tau Pathology

Abnormalities in glucose metabolism and misfolded protein deposits composed of the amyloid-{beta} peptide (A{beta}) and tau are the three most common neuropathological hallmarks of Alzheimers disease (AD), but their relationship(s) to the disease process or to each other largely remains unclear. In this report, the first human brain quantitative lysine succinylome together with a global proteome analysis from controls and patients reveals that lysine succinylation contributes to these three key AD-related pathologies. Succinylation, a newly discovered protein post-translational modification (PTM), of multiple proteins, particularly mitochondrial proteins, declines with the progression of AD. In contrast, amyloid precursor protein (APP) and tau consistently exhibit the largest AD-related increases in succinylation, occurring at specific sites in AD brains but never in controls. Transgenic mouse studies demonstrate that succinylated APP and succinylated tau are detectable in the hippocampus concurrent with A{beta} assemblies in the oligomer and insoluble fiber assembly states. Multiple biochemical approaches revealed that succinylation of APP alters APP processing so as to promote A{beta} accumulation, while succinylation of tau promotes its aggregation and impairs its microtubule binding ability. Succinylation, therefore, is the first single PTM that can be added in parallel to multiple substrates, thereby promoting amyloidosis, tauopathy, and glucose hypometabolism. These data raise the possibility that, in order to show meaningful clinical benefit, any therapeutic and/or preventative measures destined for success must have an activity to either prevent or reverse the molecular pathologies attributable to excess succinylation.

neuroscience↗