Davies, M. C. | bioRxiv Science

bioRxiv2024

Staphylococcus aureus gliding comets: formation and observation

Staphylococcus aureus has been shown to move across soft agar surfaces by several different mechanisms. S. aureus can move using either spreading (a form of sliding motility producing generally round/frond like colonies) or by forming comets (slime covered aggregates of cells) that result in long thin dendrites branching out from the central colony. Spreading is agreed to be a form of passive motility whilst the comets are a form of gliding motility (i.e. active). Comets occur under similar conditions to spreading round colonies; however it can be difficult to get the comets to form. Here we examine the variables involved in determining whether comets form as well as report further observations of the comets themselves. We found that the conditions that favoured comet formation (and formed the associated dendrites) occurred over a more limited range than those that enabled spreading motility. Comet formation is very sensitive to the solidifying agents used, the amount of media used and the drying time. We further observed that the comets can propel themselves upwards against gravity unlike spreading motility and that S. aureus formed unusual dense aggregates and strand-like structures within comets unlike the normal growing arrangement of S. aureus observed in spreading. These results may aid others in producing motility assays to study spreading and comet formation in S. aureus and provides further insight into how comets behave.

microbiology↗

bioRxiv2023

Reduced S-acylation of SQSTM1/p62 in Huntington disease is associated with impaired autophagy

Disruption of macroautophagy/autophagy has emerged as a common feature in many neurodegenerative diseases. Autophagy is a membrane-dependent pathway that requires many key regulators to quickly localize on and off membranes during induction promoting membrane fusion. Previously, our bioinformatic approaches have shown that autophagy and Huntington disease (HD) are enriched in S-acylated proteins. S-acylation involves the reversible addition of long chain fatty acids to promote membrane binding. Herein, we show that inhibition of S-acylation regulates the abundance of several key regulators of autophagy and leads to a partial block of autophagic flux. We show that the autophagy receptor SQSTM1/p62 (sequestosome 1) is S-acylated and directed to the lysosome. Importantly, we see that SQSTM1 S-acylation is significantly reduced in HD patient and mouse model brains, thus providing a novel mechanism for the generation of empty autophagosomes previously seen in HD models and patient cells.

neuroscience↗