Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei

Abstract Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a disease endemic to the tropics. Melioidosis manifests in various ways ranging from acute skin lesions to pneumonia and, in rare cases, infection of the central nervous system. Bp is a facultative intracellular pathogen...

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Autores principales:	Ian A. McMillan, Michael H. Norris, Jan Zarzycki-Siek, Yun Heacock-Kang, Zhenxin Sun, Bradley R. Borlee, Tung T. Hoang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a606c0c40294f318291d70f6efd0580
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spelling	oai:doaj.org-article:7a606c0c40294f318291d70f6efd05802021-12-02T15:52:25ZIdentification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei10.1038/s41598-021-89852-72045-2322https://doaj.org/article/7a606c0c40294f318291d70f6efd05802021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89852-7https://doaj.org/toc/2045-2322Abstract Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a disease endemic to the tropics. Melioidosis manifests in various ways ranging from acute skin lesions to pneumonia and, in rare cases, infection of the central nervous system. Bp is a facultative intracellular pathogen and it can infect various cell types. The Bp intracellular lifecycle has been partially elucidated and is highly complex. Herein, we have identified a transcriptional regulator, BP1026B_II1198, that is differentially expressed as Bp transits through host cells. A deletion mutant of BP1026B_II1198 was attenuated in RAW264.7 cell and BALB/c mouse infection. To further characterize the function of this transcriptional regulator, we endeavored to determine the regulon of BP1026B_II1198. RNA-seq analysis showed the global picture of genes regulated while ChIP-seq analysis identified two specific BP1026B_II1198 binding regions on chromosome II. We investigated the transposon mutants of these genes controlled by BP1026B_II1198 and confirmed that these genes contribute to pathogenesis in RAW264.7 murine macrophage cells. Taken together, the data presented here shed light on the regulon of BP1026B_II1198 and its role during intracellular infection and highlights an integral portion of the highly complex regulation network of Bp during host infection.Ian A. McMillanMichael H. NorrisJan Zarzycki-SiekYun Heacock-KangZhenxin SunBradley R. BorleeTung T. HoangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ian A. McMillan Michael H. Norris Jan Zarzycki-Siek Yun Heacock-Kang Zhenxin Sun Bradley R. Borlee Tung T. Hoang Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei
description	Abstract Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a disease endemic to the tropics. Melioidosis manifests in various ways ranging from acute skin lesions to pneumonia and, in rare cases, infection of the central nervous system. Bp is a facultative intracellular pathogen and it can infect various cell types. The Bp intracellular lifecycle has been partially elucidated and is highly complex. Herein, we have identified a transcriptional regulator, BP1026B_II1198, that is differentially expressed as Bp transits through host cells. A deletion mutant of BP1026B_II1198 was attenuated in RAW264.7 cell and BALB/c mouse infection. To further characterize the function of this transcriptional regulator, we endeavored to determine the regulon of BP1026B_II1198. RNA-seq analysis showed the global picture of genes regulated while ChIP-seq analysis identified two specific BP1026B_II1198 binding regions on chromosome II. We investigated the transposon mutants of these genes controlled by BP1026B_II1198 and confirmed that these genes contribute to pathogenesis in RAW264.7 murine macrophage cells. Taken together, the data presented here shed light on the regulon of BP1026B_II1198 and its role during intracellular infection and highlights an integral portion of the highly complex regulation network of Bp during host infection.
format	article
author	Ian A. McMillan Michael H. Norris Jan Zarzycki-Siek Yun Heacock-Kang Zhenxin Sun Bradley R. Borlee Tung T. Hoang
author_facet	Ian A. McMillan Michael H. Norris Jan Zarzycki-Siek Yun Heacock-Kang Zhenxin Sun Bradley R. Borlee Tung T. Hoang
author_sort	Ian A. McMillan
title	Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei
title_short	Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei
title_full	Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei
title_fullStr	Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei
title_full_unstemmed	Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei
title_sort	identification of a padr-type regulator essential for intracellular pathogenesis of burkholderia pseudomallei
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7a606c0c40294f318291d70f6efd0580
work_keys_str_mv	AT ianamcmillan identificationofapadrtyperegulatoressentialforintracellularpathogenesisofburkholderiapseudomallei AT michaelhnorris identificationofapadrtyperegulatoressentialforintracellularpathogenesisofburkholderiapseudomallei AT janzarzyckisiek identificationofapadrtyperegulatoressentialforintracellularpathogenesisofburkholderiapseudomallei AT yunheacockkang identificationofapadrtyperegulatoressentialforintracellularpathogenesisofburkholderiapseudomallei AT zhenxinsun identificationofapadrtyperegulatoressentialforintracellularpathogenesisofburkholderiapseudomallei AT bradleyrborlee identificationofapadrtyperegulatoressentialforintracellularpathogenesisofburkholderiapseudomallei AT tungthoang identificationofapadrtyperegulatoressentialforintracellularpathogenesisofburkholderiapseudomallei
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Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei

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