The KdpD/KdpE Two-Component System: Integrating K+ Homeostasis and Virulence
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{"title"=>"The KdpD/KdpE Two-Component System: Integrating K+ Homeostasis and Virulence", "type"=>"journal", "authors"=>[{"first_name"=>"Zoë N.", "last_name"=>"Freeman", "scopus_author_id"=>"24922727800"}, {"first_name"=>"Steve", "last_name"=>"Dorus", "scopus_author_id"=>"6603319324"}, {"first_name"=>"Nicholas R.", "last_name"=>"Waterfield", "scopus_author_id"=>"6601935218"}], "year"=>2013, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"84875972434", "doi"=>"10.1371/journal.ppat.1003201", "pui"=>"368694499", "issn"=>"15537366", "pmid"=>"23555240", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "scopus"=>"2-s2.0-84875972434"}, "id"=>"7832563a-8af7-3ec3-9259-9b3fc69429ec", "abstract"=>"The two-component system (TCS) KdpD/KdpE, extensively studied for its regulatory role in potassium (K(+)) transport, has more recently been identified as an adaptive regulator involved in the virulence and intracellular survival of pathogenic bacteria, including Staphylococcus aureus, entero-haemorrhagic Escherichia coli, Salmonella typhimurium, Yersinia pestis, Francisella species, Photorhabdus asymbiotica, and mycobacteria. Key homeostasis requirements monitored by KdpD/KdpE and other TCSs such as PhoP/PhoQ are critical to survival in the stressful conditions encountered by pathogens during host interactions. It follows these TCSs may therefore acquire adaptive roles in response to selective pressures associated with adopting a pathogenic lifestyle. Given the central role of K(+) in virulence, we propose that KdpD/KdpE, as a regulator of a high-affinity K(+) pump, has evolved virulence-related regulatory functions. In support of this hypothesis, we review the role of KdpD/KdpE in bacterial infection and summarize evidence that (i) KdpD/KdpE production is correlated with enhanced virulence and survival, (ii) KdpE regulates a range of virulence loci through direct promoter binding, and (iii) KdpD/KdpE regulation responds to virulence-related conditions including phagocytosis, exposure to microbicides, quorum sensing signals, and host hormones. Furthermore, antimicrobial stress, osmotic stress, and oxidative stress are associated with KdpD/KdpE activity, and the system's accessory components (which allow TCS fine-tuning or crosstalk) provide links to stress response pathways. KdpD/KdpE therefore appears to be an important adaptive TCS employed during host infection, promoting bacterial virulence and survival through mechanisms both related to and distinct from its conserved role in K(+) regulation.", "link"=>"http://www.mendeley.com/research/kdpdkdpe-twocomponent-system-integrating-k-homeostasis-virulence", "reader_count"=>93, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>7, "Student > Doctoral Student"=>8, "Researcher"=>17, "Student > Ph. D. Student"=>24, "Student > Postgraduate"=>6, "Student > Master"=>13, "Student > Bachelor"=>11, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>7, "Student > Doctoral Student"=>8, "Researcher"=>17, "Student > Ph. D. Student"=>24, "Student > Postgraduate"=>6, "Student > Master"=>13, "Student > Bachelor"=>11, "Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Engineering"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>15, "Agricultural and Biological Sciences"=>57, "Medicine and Dentistry"=>2, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>7}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>7}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>57}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>15}, "Unspecified"=>{"Unspecified"=>7}, "Environmental Science"=>{"Environmental Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Greece"=>1, "Belgium"=>1, "United States"=>1, "France"=>2, "Chile"=>1, "India"=>2, "Russia"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1001246"], "description"=>"<p>(A) The conventional model is that KdpD/KdpE stimulates transcription of the Kdp-ATPase in response to cytoplasmic ionic and ATP concentrations and possibly also turgor pressure <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Brandon1\" target=\"_blank\">[9]</a>. (B) In <i>S. aureus</i> KdpD is affected directly or indirectly by QS systems, and KdpE regulates many downstream genes including virulence factors by directly binding to their promoters <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Xue1\" target=\"_blank\">[17]</a>, <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Zhao1\" target=\"_blank\">[18]</a>. (C) In EHEC, KdpE can also be activated by the QseC histidine kinase, which senses host adrenergic signals as well as bacterial quorum sensing (QS) signals <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Hughes1\" target=\"_blank\">[24]</a>. In vitro its regulatory targets include the <i>ler</i> gene, which controls the “locus of enterocyte effacement\" (LEE) genes. Under gluconeogenic conditions, KdpE interacts with Cra to optimally regulate <i>ler</i>; both proteins bind to the promoter, perhaps through bending of the DNA <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Njoroge1\" target=\"_blank\">[25]</a>. The downstream regulatory cascade is integral to lesion formation in the host gut <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Hughes1\" target=\"_blank\">[24]</a>, <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Njoroge1\" target=\"_blank\">[25]</a>. (D) Recently identified accessory components in nonpathogenic <i>E. coli</i> link the pathway to additional input stimuli or modulate KdpD activity <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Lttmann1\" target=\"_blank\">[34]</a>, <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Heermann4\" target=\"_blank\">[37]</a>, <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Sardesai1\" target=\"_blank\">[50]</a>.</p>", "links"=>[], "tags"=>["diagram", "varied", "accessory"], "article_id"=>662679, "categories"=>["Microbiology"], "users"=>["Zoë N. Freeman", "Steve Dorus", "Nicholas R. Waterfield"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003201.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_diagram_of_the_varied_inputs_accessory_proteins_and_regulatory_effects_of_KdpD_KdpE_/662679", "title"=>"Schematic diagram of the varied inputs, accessory proteins, and regulatory effects of KdpD/KdpE.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 14:55:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001247"], "description"=>"<p>Evidence supporting the role of KdpD/KdpE in virulence (V) or survival (S) is indicated across diverse bacterial species, all of which are capable of intracellular replication to some extent. The relevant references are also indicated. Phylogenetic relationships are as suggested by Battistuzzi et al. (2004) (not drawn to scale) <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003201#ppat.1003201-Battistuzzi1\" target=\"_blank\">[51]</a>.</p>", "links"=>[], "tags"=>["virulence-related", "bacterial"], "article_id"=>662680, "categories"=>["Microbiology"], "users"=>["Zoë N. Freeman", "Steve Dorus", "Nicholas R. Waterfield"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003201.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_KdpD_KdpE_virulence_related_roles_across_bacterial_taxa_/662680", "title"=>"KdpD/KdpE virulence-related roles across bacterial taxa.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 14:55:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1013683"], "description"=>"<p>Evidence supporting the role of KdpD/KdpE in bacterial virulence and survival in cell or animal models.</p>", "links"=>[], "tags"=>["supporting", "bacterial", "virulence"], "article_id"=>674094, "categories"=>["Microbiology"], "users"=>["Zoë N. Freeman", "Steve Dorus", "Nicholas R. Waterfield"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003201.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evidence_supporting_the_role_of_KdpD_KdpE_in_bacterial_virulence_and_survival_in_cell_or_animal_models_/674094", "title"=>"Evidence supporting the role of KdpD/KdpE in bacterial virulence and survival in cell or animal models.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-28 01:08:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1013698"], "description"=>"<p>Evidence that KdpD/KdpE plays a role in resisting stresses.</p>", "links"=>[], "tags"=>["resisting"], "article_id"=>674113, "categories"=>["Microbiology"], "users"=>["Zoë N. Freeman", "Steve Dorus", "Nicholas R. Waterfield"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003201.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evidence_that_KdpD_KdpE_plays_a_role_in_resisting_stresses_/674113", "title"=>"Evidence that KdpD/KdpE plays a role in resisting stresses.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-28 01:08:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1013718"], "description"=>"<p>Identification of KdpD accessory components in <i>E. coli</i> and <i>M. tuberculosis</i>.</p>", "links"=>[], "tags"=>["kdpd", "accessory", "components"], "article_id"=>674125, "categories"=>["Microbiology"], "users"=>["Zoë N. Freeman", "Steve Dorus", "Nicholas R. Waterfield"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003201.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_KdpD_accessory_components_in_E_coli_and_M_tuberculosis_/674125", "title"=>"Identification of KdpD accessory components in <i>E. coli</i> and <i>M. tuberculosis</i>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-28 01:08:45"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
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  • {"unique-ip"=>"24", "full-text"=>"31", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
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  • {"unique-ip"=>"24", "full-text"=>"24", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
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  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"19", "full-text"=>"21", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
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  • {"unique-ip"=>"22", "full-text"=>"21", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[284, 491, 620, 738, 843, 945, 1043, 1137, 1225, 1315, 1400, 1479, 1555]}, {"subject_area"=>"/Biology and life sciences/Microbiology", "average_usage"=>[293, 503, 638, 755, 861, 960, 1056, 1146, 1239, 1323, 1403, 1491, 1568]}, {"subject_area"=>"/Biology and life sciences/Organisms", "average_usage"=>[281, 484, 611, 728, 835, 934, 1030, 1123, 1214, 1299, 1383, 1464]}, {"subject_area"=>"/Biology and life sciences/Physiology", "average_usage"=>[256, 449, 572, 676, 775, 866, 955, 1041, 1127, 1213, 1290, 1370, 1437]}, {"subject_area"=>"/Medicine and health sciences/Pathology and laboratory medicine", "average_usage"=>[267, 466, 592, 709, 806, 901, 989, 1075, 1162, 1254, 1342, 1424, 1486]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[258, 449, 572, 679, 775, 866, 956, 1041, 1124, 1211, 1291, 1371, 1437]}]}
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