Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis

<p<Abstract</p< <p<Background</p< <p<Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct <it<Mycobacteriu...
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Autor*in:	Be Nicholas A [verfasserIn] Bishai William R [verfasserIn] Jain Sanjay K [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2012

Übergeordnetes Werk:	In: BMC Microbiology - BMC, 2003, 12(2012), 1, p 7
Übergeordnetes Werk:	volume:12 ; year:2012 ; number:1, p 7

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/1471-2180-12-7

Katalog-ID:	DOAJ007874332

Internformat


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allfields	10.1186/1471-2180-12-7 doi (DE-627)DOAJ007874332 (DE-599)DOAJf9ca8e94d83f4c3a9b1864fc1a834326 DE-627 ger DE-627 rakwb eng QR1-502 Be Nicholas A verfasserin aut Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct <it<Mycobacterium tuberculosis </it<strains with central nervous system disease, the microbial virulence factors required have not been described previously.</p< <p<Results</p< <p<We screened 398 unique <it<M. tuberculosis </it<mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found <it<M. tuberculosis pknD </it<(<it<Rv0931c</it<) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that <it<pknD </it<is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. <it<M. tuberculosis pknD </it<encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the <it<M. tuberculosis </it<PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum.</p< <p<Conclusions</p< <p<Our findings demonstrate a novel <it<in vivo </it<role for <it<M. tuberculosis pknD </it<and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.</p< Microbiology Bishai William R verfasserin aut Jain Sanjay K verfasserin aut In BMC Microbiology BMC, 2003 12(2012), 1, p 7 (DE-627)326644997 (DE-600)2041505-9 14712180 nnns volume:12 year:2012 number:1, p 7 https://doi.org/10.1186/1471-2180-12-7 kostenfrei https://doaj.org/article/f9ca8e94d83f4c3a9b1864fc1a834326 kostenfrei http://www.biomedcentral.com/1471-2180/12/7 kostenfrei https://doaj.org/toc/1471-2180 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2012 1, p 7
spelling	10.1186/1471-2180-12-7 doi (DE-627)DOAJ007874332 (DE-599)DOAJf9ca8e94d83f4c3a9b1864fc1a834326 DE-627 ger DE-627 rakwb eng QR1-502 Be Nicholas A verfasserin aut Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct <it<Mycobacterium tuberculosis </it<strains with central nervous system disease, the microbial virulence factors required have not been described previously.</p< <p<Results</p< <p<We screened 398 unique <it<M. tuberculosis </it<mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found <it<M. tuberculosis pknD </it<(<it<Rv0931c</it<) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that <it<pknD </it<is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. <it<M. tuberculosis pknD </it<encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the <it<M. tuberculosis </it<PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum.</p< <p<Conclusions</p< <p<Our findings demonstrate a novel <it<in vivo </it<role for <it<M. tuberculosis pknD </it<and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.</p< Microbiology Bishai William R verfasserin aut Jain Sanjay K verfasserin aut In BMC Microbiology BMC, 2003 12(2012), 1, p 7 (DE-627)326644997 (DE-600)2041505-9 14712180 nnns volume:12 year:2012 number:1, p 7 https://doi.org/10.1186/1471-2180-12-7 kostenfrei https://doaj.org/article/f9ca8e94d83f4c3a9b1864fc1a834326 kostenfrei http://www.biomedcentral.com/1471-2180/12/7 kostenfrei https://doaj.org/toc/1471-2180 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2012 1, p 7
allfields_unstemmed	10.1186/1471-2180-12-7 doi (DE-627)DOAJ007874332 (DE-599)DOAJf9ca8e94d83f4c3a9b1864fc1a834326 DE-627 ger DE-627 rakwb eng QR1-502 Be Nicholas A verfasserin aut Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct <it<Mycobacterium tuberculosis </it<strains with central nervous system disease, the microbial virulence factors required have not been described previously.</p< <p<Results</p< <p<We screened 398 unique <it<M. tuberculosis </it<mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found <it<M. tuberculosis pknD </it<(<it<Rv0931c</it<) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that <it<pknD </it<is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. <it<M. tuberculosis pknD </it<encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the <it<M. tuberculosis </it<PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum.</p< <p<Conclusions</p< <p<Our findings demonstrate a novel <it<in vivo </it<role for <it<M. tuberculosis pknD </it<and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.</p< Microbiology Bishai William R verfasserin aut Jain Sanjay K verfasserin aut In BMC Microbiology BMC, 2003 12(2012), 1, p 7 (DE-627)326644997 (DE-600)2041505-9 14712180 nnns volume:12 year:2012 number:1, p 7 https://doi.org/10.1186/1471-2180-12-7 kostenfrei https://doaj.org/article/f9ca8e94d83f4c3a9b1864fc1a834326 kostenfrei http://www.biomedcentral.com/1471-2180/12/7 kostenfrei https://doaj.org/toc/1471-2180 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2012 1, p 7
allfieldsGer	10.1186/1471-2180-12-7 doi (DE-627)DOAJ007874332 (DE-599)DOAJf9ca8e94d83f4c3a9b1864fc1a834326 DE-627 ger DE-627 rakwb eng QR1-502 Be Nicholas A verfasserin aut Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct <it<Mycobacterium tuberculosis </it<strains with central nervous system disease, the microbial virulence factors required have not been described previously.</p< <p<Results</p< <p<We screened 398 unique <it<M. tuberculosis </it<mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found <it<M. tuberculosis pknD </it<(<it<Rv0931c</it<) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that <it<pknD </it<is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. <it<M. tuberculosis pknD </it<encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the <it<M. tuberculosis </it<PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum.</p< <p<Conclusions</p< <p<Our findings demonstrate a novel <it<in vivo </it<role for <it<M. tuberculosis pknD </it<and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.</p< Microbiology Bishai William R verfasserin aut Jain Sanjay K verfasserin aut In BMC Microbiology BMC, 2003 12(2012), 1, p 7 (DE-627)326644997 (DE-600)2041505-9 14712180 nnns volume:12 year:2012 number:1, p 7 https://doi.org/10.1186/1471-2180-12-7 kostenfrei https://doaj.org/article/f9ca8e94d83f4c3a9b1864fc1a834326 kostenfrei http://www.biomedcentral.com/1471-2180/12/7 kostenfrei https://doaj.org/toc/1471-2180 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2012 1, p 7
allfieldsSound	10.1186/1471-2180-12-7 doi (DE-627)DOAJ007874332 (DE-599)DOAJf9ca8e94d83f4c3a9b1864fc1a834326 DE-627 ger DE-627 rakwb eng QR1-502 Be Nicholas A verfasserin aut Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct <it<Mycobacterium tuberculosis </it<strains with central nervous system disease, the microbial virulence factors required have not been described previously.</p< <p<Results</p< <p<We screened 398 unique <it<M. tuberculosis </it<mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found <it<M. tuberculosis pknD </it<(<it<Rv0931c</it<) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that <it<pknD </it<is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. <it<M. tuberculosis pknD </it<encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the <it<M. tuberculosis </it<PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum.</p< <p<Conclusions</p< <p<Our findings demonstrate a novel <it<in vivo </it<role for <it<M. tuberculosis pknD </it<and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.</p< Microbiology Bishai William R verfasserin aut Jain Sanjay K verfasserin aut In BMC Microbiology BMC, 2003 12(2012), 1, p 7 (DE-627)326644997 (DE-600)2041505-9 14712180 nnns volume:12 year:2012 number:1, p 7 https://doi.org/10.1186/1471-2180-12-7 kostenfrei https://doaj.org/article/f9ca8e94d83f4c3a9b1864fc1a834326 kostenfrei http://www.biomedcentral.com/1471-2180/12/7 kostenfrei https://doaj.org/toc/1471-2180 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2012 1, p 7
language	English
source	In BMC Microbiology 12(2012), 1, p 7 volume:12 year:2012 number:1, p 7
sourceStr	In BMC Microbiology 12(2012), 1, p 7 volume:12 year:2012 number:1, p 7
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institution	findex.gbv.de
topic_facet	Microbiology
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container_title	BMC Microbiology
authorswithroles_txt_mv	Be Nicholas A @@aut@@ Bishai William R @@aut@@ Jain Sanjay K @@aut@@
publishDateDaySort_date	2012-01-01T00:00:00Z
hierarchy_top_id	326644997
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spellingShingle	Be Nicholas A misc QR1-502 misc Microbiology Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis
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topic_title	QR1-502 Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis
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title	Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis
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title_full	Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis
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title_sort	role of <it<mycobacterium tuberculosis pknd </it<in the pathogenesis of central nervous system tuberculosis
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title_auth	Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis
abstract	<p<Abstract</p< <p<Background</p< <p<Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct <it<Mycobacterium tuberculosis </it<strains with central nervous system disease, the microbial virulence factors required have not been described previously.</p< <p<Results</p< <p<We screened 398 unique <it<M. tuberculosis </it<mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found <it<M. tuberculosis pknD </it<(<it<Rv0931c</it<) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that <it<pknD </it<is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. <it<M. tuberculosis pknD </it<encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the <it<M. tuberculosis </it<PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum.</p< <p<Conclusions</p< <p<Our findings demonstrate a novel <it<in vivo </it<role for <it<M. tuberculosis pknD </it<and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.</p<
abstractGer	<p<Abstract</p< <p<Background</p< <p<Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct <it<Mycobacterium tuberculosis </it<strains with central nervous system disease, the microbial virulence factors required have not been described previously.</p< <p<Results</p< <p<We screened 398 unique <it<M. tuberculosis </it<mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found <it<M. tuberculosis pknD </it<(<it<Rv0931c</it<) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that <it<pknD </it<is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. <it<M. tuberculosis pknD </it<encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the <it<M. tuberculosis </it<PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum.</p< <p<Conclusions</p< <p<Our findings demonstrate a novel <it<in vivo </it<role for <it<M. tuberculosis pknD </it<and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.</p<
abstract_unstemmed	<p<Abstract</p< <p<Background</p< <p<Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct <it<Mycobacterium tuberculosis </it<strains with central nervous system disease, the microbial virulence factors required have not been described previously.</p< <p<Results</p< <p<We screened 398 unique <it<M. tuberculosis </it<mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found <it<M. tuberculosis pknD </it<(<it<Rv0931c</it<) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that <it<pknD </it<is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. <it<M. tuberculosis pknD </it<encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the <it<M. tuberculosis </it<PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum.</p< <p<Conclusions</p< <p<Our findings demonstrate a novel <it<in vivo </it<role for <it<M. tuberculosis pknD </it<and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.</p<
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title_short	Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis
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Role of <it<Mycobacterium tuberculosis pknD </it<in the Pathogenesis of central nervous system tuberculosis

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