Chemical Inhibition of Bacterial Protein Tyrosine Phosphatase Suppresses Capsule Production
- Publication Date
- May 15, 2012
- Journal
- PLOS ONE
- Authors
- Alistair J. Standish, Angela A. Salim, Hua Zhang, Robert J. Capon, et al
- Volume
- 7
- Issue
- 5
- Pages
- e36312
- DOI
- https://dx.plos.org/10.1371/journal.pone.0036312
- Publisher URL
- http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0036312
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/22629313
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356977
- Europe PMC
- http://europepmc.org/abstract/MED/22629313
- Web of Science
- 000305336300014
- Scopus
- 84866917514
- Mendeley
- http://www.mendeley.com/research/chemical-inhibition-bacterial-protein-tyrosine-phosphatase-suppresses-capsule-production
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Mendeley | Further Information
{"title"=>"Chemical Inhibition of Bacterial Protein Tyrosine Phosphatase Suppresses Capsule Production", "type"=>"journal", "authors"=>[{"first_name"=>"Alistair J.", "last_name"=>"Standish"}, {"first_name"=>"Angela A.", "last_name"=>"Salim"}, {"first_name"=>"Hua", "last_name"=>"Zhang"}, {"first_name"=>"Robert J.", "last_name"=>"Capon"}, {"first_name"=>"Renato", "last_name"=>"Morona"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"22629313", "issn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0036312", "pui"=>"366356961", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84866917514", "sgr"=>"84866917514"}, "id"=>"534e416a-9db6-3f19-a4f6-b195a297e045", "abstract"=>"Capsule polysaccharide is a major virulence factor for a wide range of bacterial pathogens, including Streptococcus pneumoniae. The biosynthesis of Wzy-dependent capsules in both gram-negative and -positive bacteria is regulated by a system involving a protein tyrosine phosphatase (PTP) and a protein tyrosine kinase. However, how the system functions is still controversial. In Streptococcus pneumoniae, a major human pathogen, the system is present in all but 2 of the 93 serotypes found to date. In order to study this regulation further, we performed a screen to find inhibitors of the phosphatase, CpsB. This led to the observation that a recently discovered marine sponge metabolite, fascioquinol E, inhibited CpsB phosphatase activity both in vitro and in vivo at concentrations that did not affect the growth of the bacteria. This inhibition resulted in decreased capsule synthesis in D39 and Type 1 S. pneumoniae. Furthermore, concentrations of Fascioquinol E that inhibited capsule also lead to increased attachment of pneumococci to a macrophage cell line, suggesting that this compound would inhibit the virulence of the pathogen. Interestingly, this compound also inhibited the phosphatase activity of the structurally unrelated gram-negative PTP, Wzb, which belongs to separate family of protein tyrosine phosphatases. Furthermore, incubation with Klebsiella pneumoniae, which contains a homologous phosphatase, resulted in decreased capsule synthesis. Taken together, these data provide evidence that PTPs are critical for Wzy-dependent capsule production across a spectrum of bacteria, and as such represents a valuable new molecular target for the development of anti-virulence antibacterials.", "link"=>"http://www.mendeley.com/research/chemical-inhibition-bacterial-protein-tyrosine-phosphatase-suppresses-capsule-production", "reader_count"=>34, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>5, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>5, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>18, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>2, "Immunology and Microbiology"=>1, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Environmental Science"=>{"Environmental Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"China"=>1}, "group_count"=>1}CrossRef
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Scopus | Further Information
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Relative Metric
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