Publications by authors named "Aditya K Pal"
Article Synopsis
- High mortality rates from tuberculosis and other bacterial infections are largely due to drug resistance development, and research on bacterial second messenger molecules in antibiotic tolerance is limited.
- This study reveals that the concentration of cyclic di-AMP (c-di-AMP) in Mycobacterium smegmatis affects its drug sensitivity by interacting with certain proteins and mRNA regions, leading to decreased gene expression.
- The researchers explored the effects of four different antibiotics and found that higher levels of c-di-AMP are linked to increased sensitivity to the drugs, identifying specific genes and pathways influenced by c-di-AMP.
Bacterial second messenger signaling often plays an important role in cellular physiology. In this study, we have attempted to understand how c-di-AMP synthesis and degradation are transcriptionally regulated in . We found that although a c-di-AMP synthesis gene, , exists in a multi-gene operon, a sub-operon promoter arrangement facilitates gene expression under normal conditions to maintain intracellular c-di-AMP concentration and is induced further during certain stress adaptations.
View Article and Find Full Text PDFHyperphosphorylated nucleotide (p)ppGpp, synthesized by Rel protein, regulates the stringent response pathway responsible for biofilm and persister cell growth in mycobacteria. The discovery of vitamin C as an inhibitor of Rel protein activities raises the prospect of tetrone lactones to prevent such pathways. The closely related isotetrone lactone derivatives are identified herein as inhibitors of the above processes in a mycobacterium.
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- - Cyclic-di-AMP (c-di-AMP) is a vital secondary messenger in Gram-positive bacteria, influencing key cellular processes and physiological traits like colony structure and cell size under varying conditions.
- - The study compared c-di-AMP null mutants and those with over-expressed c-di-AMP to understand its role in stress adaptation and biofilm formation, highlighting how its concentration affects bacterial response to DNA and membrane stress.
- - Additionally, the research explored c-di-AMP's impact on antibiotic resistance in mycobacteria, identifying critical genes and pathways involved in functions like translation and cell wall maintenance.
In this study, we probe the role of secondary messenger c-di-AMP in drug tolerance, which includes both persister and resistant mutant characterization of Mycobacterium smegmatis. Specifically, with the use of c-di-AMP null and overproducing mutants, we showed how c-di-AMP plays a significant role in resistance mutagenesis against antibiotics with different mechanisms of action. We elucidated the specific molecular mechanism linking the elevated intracellular c-di-AMP level and high mutant generation and highlighted the significance of non-homology-based DNA repair.
View Article and Find Full Text PDFThe current nightmare for the whole world is COVID-19. The occurrence of concentrated pneumonia cases in Wuhan city, Hubei province of China, was first reported on December 30, 2019. SARS-CoV first disclosed in 2002 but had not outspread worldwide.
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