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The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression.

The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression.
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Nakamya MF, Ayoola MB, Park S, Shack LA, Swiatlo E, Nanduri B,


Nakamya MF, Ayoola MB, Park S, Shack LA, Swiatlo E, Nanduri B, (click to view)

Nakamya MF, Ayoola MB, Park S, Shack LA, Swiatlo E, Nanduri B,

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Medical sciences (Basel, Switzerland) 2018 01 196(1) pii E8
Abstract

Invasive infections caused by Streptococcus pneumoniae, a commensal in the nasopharynx, pose significant risk to human health. Limited serotype coverage by the available polysaccharide-based conjugate vaccines coupled with increasing incidence of antibiotic resistance complicates therapeutic strategies. Bacterial physiology and metabolism that allows pathogens to adapt to the host are a promising avenue for the discovery of novel therapeutics. Intracellular polyamine concentrations are tightly regulated by biosynthesis, transport and degradation. We previously reported that deletion of cadA, a gene that encodes for lysine decarboxylase, an enzyme that catalyzes cadaverine synthesis results in an attenuated phenotype. Here, we report the impact of cadA deletion on pneumococcal capsule and protein expression. Our data show that genes for polyamine biosynthesis and transport are downregulated in ∆cadA. Immunoblot assays show reduced capsule in ∆cadA. Reduced capsule synthesis could be due to reduced transcription and availability of precursors for synthesis. The capsule is the predominant virulence factor in pneumococci and is critical for evading opsonophagocytosis and its loss in ∆cadA could explain the reported attenuation in vivo. Results from this study show that capsule synthesis in pneumococci is regulated by polyamine metabolism, which can be targeted for developing novel therapies.

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