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<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">FlaA Proteins in
<named-content content-type="genus-species">Leptospira interrogans</named-content>
Are Essential for Motility and Virulence but Are Not Required for Formation of the Flagellum Sheath</title>
<author>
<name sortKey="Lambert, Ambroise" sort="Lambert, Ambroise" uniqKey="Lambert A" first="Ambroise" last="Lambert">Ambroise Lambert</name>
<affiliation>
<nlm:aff id="aff1">Institut Pasteur, Unité de Biologie des Spirochètes, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Picardeau, Mathieu" sort="Picardeau, Mathieu" uniqKey="Picardeau M" first="Mathieu" last="Picardeau">Mathieu Picardeau</name>
<affiliation>
<nlm:aff id="aff1">Institut Pasteur, Unité de Biologie des Spirochètes, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Haake, David A" sort="Haake, David A" uniqKey="Haake D" first="David A." last="Haake">David A. Haake</name>
<affiliation>
<nlm:aff id="aff3">Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff4">Department of Medicine, University of California—Los Angeles School of Medicine, Los Angeles, California, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sermswan, Rasana W" sort="Sermswan, Rasana W" uniqKey="Sermswan R" first="Rasana W." last="Sermswan">Rasana W. Sermswan</name>
<affiliation>
<nlm:aff id="aff5">Department of Biochemistry, Khon Kaen University, Khon Kaen, Thailand</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff6">Melioidosis Research Center, Khon Kaen University, Khon Kaen, Thailand</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Srikram, Amporn" sort="Srikram, Amporn" uniqKey="Srikram A" first="Amporn" last="Srikram">Amporn Srikram</name>
<affiliation>
<nlm:aff id="aff6">Melioidosis Research Center, Khon Kaen University, Khon Kaen, Thailand</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Adler, Ben" sort="Adler, Ben" uniqKey="Adler B" first="Ben" last="Adler">Ben Adler</name>
<affiliation>
<nlm:aff id="aff7">Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Clayton, Australia</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Murray, Gerald A" sort="Murray, Gerald A" uniqKey="Murray G" first="Gerald A." last="Murray">Gerald A. Murray</name>
<affiliation>
<nlm:aff id="aff7">Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Clayton, Australia</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">22451522</idno>
<idno type="pmc">3370569</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370569</idno>
<idno type="RBID">PMC:3370569</idno>
<idno type="doi">10.1128/IAI.00131-12</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">001890</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001890</idno>
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<sourceDesc>
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<analytic>
<title xml:lang="en" level="a" type="main">FlaA Proteins in
<named-content content-type="genus-species">Leptospira interrogans</named-content>
Are Essential for Motility and Virulence but Are Not Required for Formation of the Flagellum Sheath</title>
<author>
<name sortKey="Lambert, Ambroise" sort="Lambert, Ambroise" uniqKey="Lambert A" first="Ambroise" last="Lambert">Ambroise Lambert</name>
<affiliation>
<nlm:aff id="aff1">Institut Pasteur, Unité de Biologie des Spirochètes, Paris, France</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Picardeau, Mathieu" sort="Picardeau, Mathieu" uniqKey="Picardeau M" first="Mathieu" last="Picardeau">Mathieu Picardeau</name>
<affiliation>
<nlm:aff id="aff1">Institut Pasteur, Unité de Biologie des Spirochètes, Paris, France</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Haake, David A" sort="Haake, David A" uniqKey="Haake D" first="David A." last="Haake">David A. Haake</name>
<affiliation>
<nlm:aff id="aff3">Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff4">Department of Medicine, University of California—Los Angeles School of Medicine, Los Angeles, California, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sermswan, Rasana W" sort="Sermswan, Rasana W" uniqKey="Sermswan R" first="Rasana W." last="Sermswan">Rasana W. Sermswan</name>
<affiliation>
<nlm:aff id="aff5">Department of Biochemistry, Khon Kaen University, Khon Kaen, Thailand</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff6">Melioidosis Research Center, Khon Kaen University, Khon Kaen, Thailand</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Srikram, Amporn" sort="Srikram, Amporn" uniqKey="Srikram A" first="Amporn" last="Srikram">Amporn Srikram</name>
<affiliation>
<nlm:aff id="aff6">Melioidosis Research Center, Khon Kaen University, Khon Kaen, Thailand</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Adler, Ben" sort="Adler, Ben" uniqKey="Adler B" first="Ben" last="Adler">Ben Adler</name>
<affiliation>
<nlm:aff id="aff7">Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Clayton, Australia</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Murray, Gerald A" sort="Murray, Gerald A" uniqKey="Murray G" first="Gerald A." last="Murray">Gerald A. Murray</name>
<affiliation>
<nlm:aff id="aff7">Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Clayton, Australia</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Infection and Immunity</title>
<idno type="ISSN">0019-9567</idno>
<idno type="eISSN">1098-5522</idno>
<imprint>
<date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Spirochetes have periplasmic flagella composed of a core surrounded by a sheath. The pathogen
<named-content content-type="genus-species">Leptospira interrogans</named-content>
has four
<italic>flaB</italic>
(proposed core subunit) and two
<italic>flaA</italic>
(proposed sheath subunit) genes. The
<italic>flaA</italic>
genes are organized in a locus with
<italic>flaA2</italic>
immediately upstream of
<italic>flaA1</italic>
. In this study,
<italic>flaA1</italic>
and
<italic>flaA2</italic>
mutants were constructed by transposon mutagenesis. Both mutants still produced periplasmic flagella. The
<italic>flaA1</italic>
mutant did not produce FlaA1 but continued to produce FlaA2 and retained normal morphology and virulence in a hamster model of infection but had reduced motility. The
<italic>flaA2</italic>
mutant did not produce either the FlaA1 or the FlaA2 protein. Cells of the
<italic>flaA2</italic>
mutant lacked the distinctive hook-shaped ends associated with
<named-content content-type="genus-species">L. interrogans</named-content>
and lacked translational motility in liquid and semisolid media. These observations were confirmed with a second, independent
<italic>flaA2</italic>
mutant. The
<italic>flaA2</italic>
mutant failed to cause disease in animal models of acute infection. Despite lacking FlaA proteins, the flagella of the
<italic>flaA2</italic>
mutant were of the same thickness as wild-type flagella, as measured by electron microscopy, and exhibited a normal flagellum sheath, indicating that FlaA proteins are not essential for the synthesis of the flagellum sheath, as observed for other spirochetes. This study shows that FlaA subunits contribute to leptospiral translational motility, cellular shape, and virulence.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Infect Immun</journal-id>
<journal-id journal-id-type="iso-abbrev">Infect. Immun</journal-id>
<journal-id journal-id-type="hwp">iai</journal-id>
<journal-id journal-id-type="pmc">iai</journal-id>
<journal-id journal-id-type="publisher-id">IAI</journal-id>
<journal-title-group>
<journal-title>Infection and Immunity</journal-title>
</journal-title-group>
<issn pub-type="ppub">0019-9567</issn>
<issn pub-type="epub">1098-5522</issn>
<publisher>
<publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">22451522</article-id>
<article-id pub-id-type="pmc">3370569</article-id>
<article-id pub-id-type="publisher-id">00131-12</article-id>
<article-id pub-id-type="doi">10.1128/IAI.00131-12</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Bacterial Infections</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>FlaA Proteins in
<named-content content-type="genus-species">Leptospira interrogans</named-content>
Are Essential for Motility and Virulence but Are Not Required for Formation of the Flagellum Sheath</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Lambert</surname>
<given-names>Ambroise</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Picardeau</surname>
<given-names>Mathieu</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Haake</surname>
<given-names>David A.</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>c</sup>
</xref>
<xref ref-type="aff" rid="aff4">
<sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sermswan</surname>
<given-names>Rasana W.</given-names>
</name>
<xref ref-type="aff" rid="aff5">
<sup>e</sup>
</xref>
<xref ref-type="aff" rid="aff6">
<sup>f</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Srikram</surname>
<given-names>Amporn</given-names>
</name>
<xref ref-type="aff" rid="aff6">
<sup>f</sup>
</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Adler</surname>
<given-names>Ben</given-names>
</name>
<xref ref-type="aff" rid="aff7">
<sup>g</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Murray</surname>
<given-names>Gerald A.</given-names>
</name>
<xref ref-type="aff" rid="aff7">
<sup>g</sup>
</xref>
</contrib>
<aff id="aff1">
<label>a</label>
Institut Pasteur, Unité de Biologie des Spirochètes, Paris, France</aff>
<aff id="aff2">
<label>b</label>
Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France</aff>
<aff id="aff3">
<label>c</label>
Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA</aff>
<aff id="aff4">
<label>d</label>
Department of Medicine, University of California—Los Angeles School of Medicine, Los Angeles, California, USA</aff>
<aff id="aff5">
<label>e</label>
Department of Biochemistry, Khon Kaen University, Khon Kaen, Thailand</aff>
<aff id="aff6">
<label>f</label>
Melioidosis Research Center, Khon Kaen University, Khon Kaen, Thailand</aff>
<aff id="aff7">
<label>g</label>
Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Department of Microbiology, Monash University, Clayton, Australia</aff>
</contrib-group>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>McCormick</surname>
<given-names>B. A.</given-names>
</name>
<role>Editor</role>
</contrib>
</contrib-group>
<author-notes>
<corresp>Address correspondence to Ben Adler,
<email>ben.adler@monash.edu</email>
.</corresp>
<fn id="FN1" fn-type="present-address">
<label>*</label>
<p>Present address: Section of Food Technology, Faculty of Natural Resources and Agro-Industry, Kasetsart University Chalermphrakiate Sakon Nakhon Province Campus, Sakon Nakhon, Thailand.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<month>6</month>
<year>2012</year>
</pub-date>
<volume>80</volume>
<issue>6</issue>
<fpage>2019</fpage>
<lpage>2025</lpage>
<history>
<date date-type="received">
<day>6</day>
<month>2</month>
<year>2012</year>
</date>
<date date-type="rev-request">
<day>5</day>
<month>3</month>
<year>2012</year>
</date>
<date date-type="accepted">
<day>20</day>
<month>3</month>
<year>2012</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2012, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2012</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zii00612002019.pdf"></self-uri>
<abstract>
<p>Spirochetes have periplasmic flagella composed of a core surrounded by a sheath. The pathogen
<named-content content-type="genus-species">Leptospira interrogans</named-content>
has four
<italic>flaB</italic>
(proposed core subunit) and two
<italic>flaA</italic>
(proposed sheath subunit) genes. The
<italic>flaA</italic>
genes are organized in a locus with
<italic>flaA2</italic>
immediately upstream of
<italic>flaA1</italic>
. In this study,
<italic>flaA1</italic>
and
<italic>flaA2</italic>
mutants were constructed by transposon mutagenesis. Both mutants still produced periplasmic flagella. The
<italic>flaA1</italic>
mutant did not produce FlaA1 but continued to produce FlaA2 and retained normal morphology and virulence in a hamster model of infection but had reduced motility. The
<italic>flaA2</italic>
mutant did not produce either the FlaA1 or the FlaA2 protein. Cells of the
<italic>flaA2</italic>
mutant lacked the distinctive hook-shaped ends associated with
<named-content content-type="genus-species">L. interrogans</named-content>
and lacked translational motility in liquid and semisolid media. These observations were confirmed with a second, independent
<italic>flaA2</italic>
mutant. The
<italic>flaA2</italic>
mutant failed to cause disease in animal models of acute infection. Despite lacking FlaA proteins, the flagella of the
<italic>flaA2</italic>
mutant were of the same thickness as wild-type flagella, as measured by electron microscopy, and exhibited a normal flagellum sheath, indicating that FlaA proteins are not essential for the synthesis of the flagellum sheath, as observed for other spirochetes. This study shows that FlaA subunits contribute to leptospiral translational motility, cellular shape, and virulence.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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