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Novel Antibiotics from Actinomycetes Targeting Teichoic Acid PG Ligase

Author(s): Shilpa Chatterjee

Background: WTAs (Wall teichoic acids) are cell surface anionic glycopolymers, present in the peptidoglycan (PG) layer of gram-positive bacteria. Tag T, U, V enzymes are a group of proteins, which ligate WTA polymers to the peptidoglycan. Previous research studies, have identified seven actinomycetes strains as Tag TUV inhibitors, that displayed differential activity against B.subtilis mutant strains ΔtagTV and ΔtagUV . Aims & Objectives: To screen for differential activity and to extract and identify compounds whenever differential activity is observed. Methods: Actinomycetes strains were grown on a range of solid and liquid media, and tested for inhibitory activity against B.subtilis mutant strains ΔtagTV and ΔtagUV, using agar diffusion assays. Actinomycetes strains, exhibiting differential activity on optimized media, were chosen for large scale cultivation in bioreactors for active compound extraction. Results: Actinomycetes strains 2161 and C17P2 displayed differential activity on optimized media. These strains, when grown in 15L working volume(wv) scale bioreactors produced compounds which were differentially active on the mutant strains ΔtagTV and ΔtagUV. Active compound extraction and purification of these strains produced fractions that were differentially active. Preliminary analysis of the mass spectrophotometry data of C17P2 identified a compound with mass 520.60. Conclusions and Future work: Actinomycetes strains exhibited differential activity against B.subtilis mutant strains ΔtagTV and ΔtagUV when grown on optimized media. After media optimization, upscale and compound purification, a semipure fraction from C17P2 strain was obtained. A compound with mass of 520.60 was identified. Future work should focus on the structure elucidation of the active compound.

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