Biology subjects

Matheshwaran, S.

Publications and source records attributed to Matheshwaran, S..

3 recordsLinked to original sources

bioRxiv2023

Boronic acid derivative inhibits LexA mediated SOS response in Mycobacteria

Antimicrobial resistance (AMR) properties of several pathogens pose as one of the major global concerns demanding continuous innovation in order to be controlled. The bacterial "SOS" response, regulated by LexA and RecA, contributes to AMR through advantageous mutations. Therefore, targeting LexA/RecA system with a novel inhibitor could suppress "SOS" response and may reduce AMR. However, RecA presents a challenge as a therapeutic target due to its conservation across species, including humans. Concurrently, LexA, being absent in eukaryotes, can be potentially targeted, in part, due to its association with "SOS" response and developing AMR. Our studies combining bioinformatic, biochemical, biophysical, and cell-based assays present a unique inhibitor of mycobacterial "SOS" response wherein we show that the inhibitor interacts directly with the catalytic site residues of LexA of Mycobacterium tuberculosis (Mtb), consequently hindering its cleavage, resulting in suppression of "SOS" response. We observed important genes under the "SOS" regulon to be down-regulated in the presence of the inhibitor along with a consequent reduction in the rate of mutation frequency of mycobacterial cells. In essence, this study may facilitate further research on potential LexA inhibitors, reducing mutational rates and offering promise in mitigating AMR.

microbiology↗

bioRxiv2022

NaCl Triggers the Sessile-to-Motile Transition of Bacillus subtilis

Various chemical cues are known to alter the motile and sessile states of bacteria differentially and, in turn, the formation of biofilms. However, the underlying mechanisms at the cellular and molecular level remain less understood, which severely limits our ability to control biofilms. Here, we systematically studied the effects of NaCl on the dynamics of biofilm formation across various length scales and the associated changes in the regulation of gene expression in an undomesticated natural isolate of Bacillus subtilis. Interestingly, NaCl induced significant changes in the architecture of pellicles and yielded systematic increase in lateral expansion rates of biofilms when grown on an agar surface. At the microscopic level, both in the presence and absence of NaCl, bacteria displayed super-diffusive motion at times lesser than a second. However, at larger delay times, we observed an intriguing NaCl-induced transition from sub-diffusion behavior of individual bacterial cells to rapid diffusion behavior. In addition, NaCl reduced the dynamical heterogeneity of the bacterial cells within the biofilm. The reduced heterogeneity and the increased flagellation in a subpopulation of cells in the presence of NaCl corroborates well with the observed higher motility of the cells. Further, the cellular uptake of NaCl resulted in the downregulation of several genes underlying the formation of biofilms, revealing the role of chemical cues like NaCl in controlling the gene regulatory circuit underlying the sessile to motile transition. Our study opens a new avenue to decipher the competitive advantage provided to the subcellular populations by NaCl due to lifestyle switch in Bacillus subtilis.

microbiology↗

bioRxiv2018

Exocyst subcomplex functions in autophagosome biogenesis by regulating Atg9 trafficking

During autophagy, double membrane vesicles called autophagosomes capture and degrade the intracellular cargo. The de novo formation of autophagosomes requires several vesicle transport and membrane fusion events which are not completely understood. We studied the involvement of Exocyst- an octameric tethering complex, which has a primary function in tethering post-Golgi secretory vesicles to plasma membrane, in autophagy. Our findings indicate not all subunits of exocyst are involved in selective and general autophagy. We show that in the absence of autophagy specific subunits, autophagy arrest is accompanied by accumulation of incomplete autophagosome-like structures. In these mutants, impaired Atg9 trafficking leads to decreased delivery of membrane to the site of autophagosome biogenesis thereby impeding the elongation and completion of the autophagosomes. The subunits of exocyst which are dispensable for autophagic function do not associate with the autophagy specific subcomplex of exocyst.

cell biology↗