The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression
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 strateg...
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MDPI AG
2018-01-01
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| Series: | Medical Sciences |
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| Online Access: | http://www.mdpi.com/2076-3271/6/1/8 |
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| author | Mary F. Nakamya Moses B. Ayoola Seongbin Park Leslie A. Shack Edwin Swiatlo Bindu Nanduri |
| author_facet | Mary F. Nakamya Moses B. Ayoola Seongbin Park Leslie A. Shack Edwin Swiatlo Bindu Nanduri |
| author_sort | Mary F. Nakamya |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T00:55:50Z |
| format | Article |
| id | doaj.art-d6a37f14205040db9e332d6658b1061e |
| institution | Directory Open Access Journal |
| issn | 2076-3271 |
| language | English |
| last_indexed | 2024-04-14T00:55:50Z |
| publishDate | 2018-01-01 |
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| record_format | Article |
| series | Medical Sciences |
| spelling | doaj.art-d6a37f14205040db9e332d6658b1061e2022-12-22T02:21:38ZengMDPI AGMedical Sciences2076-32712018-01-0161810.3390/medsci6010008medsci6010008The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein ExpressionMary F. Nakamya0Moses B. Ayoola1Seongbin Park2Leslie A. Shack3Edwin Swiatlo4Bindu Nanduri5Department of Basic Sciences, College of Veterinary Medicine, P.O. Box 6100, Mississippi State, MS 39762, USADepartment of Basic Sciences, College of Veterinary Medicine, P.O. Box 6100, Mississippi State, MS 39762, USADepartment of Basic Sciences, College of Veterinary Medicine, P.O. Box 6100, Mississippi State, MS 39762, USADepartment of Basic Sciences, College of Veterinary Medicine, P.O. Box 6100, Mississippi State, MS 39762, USASection of Infectious Diseases, Southeast Louisiana Veterans Health Care System, New Orleans, LA 70112, USADepartment of Basic Sciences, College of Veterinary Medicine, P.O. Box 6100, Mississippi State, MS 39762, USAInvasive 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.http://www.mdpi.com/2076-3271/6/1/8Streptococcus pneumoniaepolyaminespneumococcal pneumoniaproteomicscapsulecomplementationmetabolismcadaverine |
| spellingShingle | Mary F. Nakamya Moses B. Ayoola Seongbin Park Leslie A. Shack Edwin Swiatlo Bindu Nanduri The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression Medical Sciences Streptococcus pneumoniae polyamines pneumococcal pneumonia proteomics capsule complementation metabolism cadaverine |
| title | The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression |
| title_full | The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression |
| title_fullStr | The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression |
| title_full_unstemmed | The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression |
| title_short | The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression |
| title_sort | role of cadaverine synthesis on pneumococcal capsule and protein expression |
| topic | Streptococcus pneumoniae polyamines pneumococcal pneumonia proteomics capsule complementation metabolism cadaverine |
| url | http://www.mdpi.com/2076-3271/6/1/8 |
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