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Balasubramanian, D.

Publications and source records attributed to Balasubramanian, D..

2 recordsLinked to original sources

Potential application of phage therapy for prophylactic treatment against Pseudomonas aeruginosa biofilm Infections.

The majority of the microbial activity in humans is in the form of biofilms, i.e., an exopolysaccharide-enclosed bacterial mass. Unlike planktonic cells and the cells on the surface of the biofilm, the biofilm-embedded cells are more resistant to the effects of the antibiotics and the host cellular defense mechanisms. A combination of biofilm growth and inherent resistance prevents effective antibiotic treatment of Pseudomonas aeruginosa infections including those in patients with cystic fibrosis. Antibiotic resistance has led to an increasing interest in alternative modalities of treatment. Thus, phages that multiply in situ and in the presence of susceptible hosts can be used as natural, self-limiting, and profoundly penetrating antibacterial agents. The objective of this study is to identify active phages against a collection of P. aeruginosa isolates (PCOR strains) including the prototype PAO1 and the isogenic constitutively alginate-producing PDO300 strains. These PCOR strains were tested against six phages (P105, P134, P140, P168, P175B, and P182). The analysis shows 69 % of the PCOR isolates are sensitive and the rest are resistant to all six phages. These phages were then tested for their ability to inhibit biofilm formation using a modified biofilm assay. The analysis demonstrated that the sensitive strains showed increased resistance, but none of the susceptible strains from the initial screening were resistant. Using the minimum biofilm eradication concentration (MBEC) assay for biofilm formation, the biofilm eradication ability of the phages was tested. The data showed that a higher volume of phage was required to eradicate preformed biofilms than the amount required to prevent colonization of planktonic cells. This data supports the idea of phage therapy more as a prophylactic treatment.

microbiology

Gene expression effects of lithium and valproic acid in a serotonergic cell line

Valproic acid (VPA) and lithium are widely used in the treatment of bipolar disorder. However, the underlying mechanism of action of these drugs is not clearly understood. We used RNA-Seq analysis to examine the global profile of gene expression in a rat serotonergic cell line (RN46A) after exposure to these two mood stabilizer drugs. Numerous genes were differentially regulated in response to VPA (log2 fold change [&ge;] 1.0; i.e. odds ratio of [&ge;] 2, at FDR <5%), but only two genes (Dynlrb2 and Cdyl2) showed significant differential regulation after exposure of the cells to lithium, with the same analysis criteria. Both of these genes were also regulated by VPA. Many of the differentially expressed genes had functions of potential relevance to mood disorders or their treatment, such as several serpin family genes (including neuroserpin), Nts (neurotensin), Maob (monoamine oxidase B) and Ap2b1, which is important for synaptic vesicle function. Pathway analysis revealed significant enrichment of Gene Ontology terms such as extracellular matrix (ECM) remodelling, cell adhesion and chemotaxis. This study in a cell line derived from the raphe nucleus has identified a range of genes and pathways that provide novel insights into the therapeutic action of the commonly used mood stabilizer drugs.

genomics