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Satardekar, R.

Publications and source records attributed to Satardekar, R..

2 recordsLinked to original sources
bioRxiv2026

From planktonic to sedentary lifestyle: Molecular dissection of the establishment and maintenance of mycobacterial biofilm

Biofilm represents a complex aggregation of bacteria embedded within a self-produced extracellular polymeric substance (EPS). We investigated the characteristics of mycobacterial biofilm using Mycobacterium smegmatis (Msm) as model organism. By combining transcriptomic (RNA-seq) and proteomic (LC-MS) analyses, the research captures dynamic changes during the establishment and maturation of the biofilm. Transcriptomics analysis showed a distinct gene expression profile as compared to its planktonic form. Interestingly, clear differences were seen between initial ([~]2-day old) and mature ([~]5-day old) biofilm stages, highlighting phasic gene expression throughout biofilm development. Marked alteration in oxidative stress-related genes and energy metabolism from ATP to NADH was observed. Furthermore, quantitative mass spectrometry-based proteome examination of EPS showed an abundance of cytoplasmic proteins present differentially between initial and mature biofilm stages. Pathway enrichment revealed enhanced oxidative stress responses and metabolic shifts in mature biofilms, including upregulation of NADH dehydrogenase and downregulation of ATP synthase, indicating altered energy metabolism. Our findings thus provide insights into the molecular adaptations, including production of mycofactocin, occurring during mycobacterial biofilm establishment and maturation, and advance our understanding of mycobacterial biofilm physiology.

microbiology↗
bioRxiv2026

Mycobacteriophage TM4 requires XylR for successful infection in Mycobacterium smegmatis mc2155

Mycobacteriophages are viruses that infect mycobacteria, including Mycobacterium tuberculosis, and have emerged as promising alternatives to antibiotics in the face of increasing antimicrobial resistance. However, evolution of phage-resistance remains a major challenge to the clinical implementation of phage therapy. We describe a TM4 phage resistant mutant in M. smegmatis harboring an in-frame deletion in the xylR, transcriptional regulator implicated in lipid metabolism, and cell envelope homeostasis. Using spontaneous mutagenesis, transcriptomics and biochemical approaches, we identify a previously uncharacterized resistance mechanism mediated by cell-envelope remodeling that impedes productive phage infection. The xylR mutation disrupted phage DNA injection through enhanced recruitment of lipooligosaccharides to the cell surface, without inhibiting phage adsorption, genome replication, and virion assembly. Remodeling of the cell envelope was further enhanced by the induction of lipooligosaccharide biosynthesis upon TM4 infection, however, the phenotype can be reverted through chemical treatment, restoring phage sensitivity. Our study expands the paradigm of innate mechanisms underlying broad-spectrum phage resistance in mycobacteria.

microbiology↗