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The solute-binding component of a putative Mn(II) ABC transporter (MntA) is a novel Bacillus anthracis virulence determinant.

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Title: The solute-binding component of a putative Mn(II) ABC transporter (MntA) is a novel Bacillus anthracis virulence determinant.
Authors: Gat, Orit, Mendelson, Itai, Chitlaru, Theodor, Ariel, Naomi, Altboum, Zeev, Levy, Haim, Weiss, Shay, Grosfeld, Haim, Cohen, Sara, Shafferman, Avigdor
Source: Molecular Microbiology; Oct2005, Vol. 58 Issue 2, p533-551, 19p, 4 Black and White Photographs, 2 Diagrams, 2 Charts, 10 Graphs
Subject Terms: ATP-binding cassette transporters, CARRIER proteins, MEMBRANE proteins, BIOLOGICAL membranes, PROTEINS, BACILLUS anthracis, BACILLUS (Bacteria), MOLECULAR biology
Abstract: Here we describe the characterization of a lipoprotein previously proposed as a potential Bacillus anthracis virulence determinant and vaccine candidate. This protein, designated MntA, is the solute-binding component of a manganese ion ATP-binding cassette transporter. Coupled proteomic-serological screen of a fully virulent wild-type B. anthracis Vollum strain, confirmed that MntA is expressed both in vitro and during infection. Expression of MntA is shown to be independent of the virulence plasmids pXO1 and pXO2. An mntA deletion, generated by allelic replacement, results in complete loss of MntA expression and its phenotypic analysis revealed: (i) impaired growth in rich media, alleviated by manganese supplementation; (ii) increased sensitivity to oxidative stress; and (iii) delayed release from cultured macrophages. The Δ mntA mutant expresses the anthrax-associated classical virulence factors, lethal toxin and capsule, in vitro as well as in vivo, and yet the mutation resulted in severe attenuation; a 104-fold drop in LD50 in a guinea pig model. MntA expressed in trans allowed to restore, almost completely, the virulence of the Δ mntA B. anthracis strain. We propose that MntA is a novel B. anthracis virulence determinant essential for the development of anthrax disease, and that B. anthracisΔ mntA strains have the potential to serve as platform for future live attenuated vaccines. [ABSTRACT FROM AUTHOR]
Copyright of Molecular Microbiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
  Group: Ti
  Data: The solute-binding component of a putative Mn(II) ABC transporter (MntA) is a novel Bacillus anthracis virulence determinant.
– Name: Author
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  Data: <searchLink fieldCode="AR" term="%22Gat%2C+Orit%22">Gat, Orit</searchLink><br /><searchLink fieldCode="AR" term="%22Mendelson%2C+Itai%22">Mendelson, Itai</searchLink><br /><searchLink fieldCode="AR" term="%22Chitlaru%2C+Theodor%22">Chitlaru, Theodor</searchLink><br /><searchLink fieldCode="AR" term="%22Ariel%2C+Naomi%22">Ariel, Naomi</searchLink><br /><searchLink fieldCode="AR" term="%22Altboum%2C+Zeev%22">Altboum, Zeev</searchLink><br /><searchLink fieldCode="AR" term="%22Levy%2C+Haim%22">Levy, Haim</searchLink><br /><searchLink fieldCode="AR" term="%22Weiss%2C+Shay%22">Weiss, Shay</searchLink><br /><searchLink fieldCode="AR" term="%22Grosfeld%2C+Haim%22">Grosfeld, Haim</searchLink><br /><searchLink fieldCode="AR" term="%22Cohen%2C+Sara%22">Cohen, Sara</searchLink><br /><searchLink fieldCode="AR" term="%22Shafferman%2C+Avigdor%22">Shafferman, Avigdor</searchLink>
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  Data: Molecular Microbiology; Oct2005, Vol. 58 Issue 2, p533-551, 19p, 4 Black and White Photographs, 2 Diagrams, 2 Charts, 10 Graphs
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22ATP-binding+cassette+transporters%22">ATP-binding cassette transporters</searchLink><br /><searchLink fieldCode="DE" term="%22CARRIER+proteins%22">CARRIER proteins</searchLink><br /><searchLink fieldCode="DE" term="%22MEMBRANE+proteins%22">MEMBRANE proteins</searchLink><br /><searchLink fieldCode="DE" term="%22BIOLOGICAL+membranes%22">BIOLOGICAL membranes</searchLink><br /><searchLink fieldCode="DE" term="%22PROTEINS%22">PROTEINS</searchLink><br /><searchLink fieldCode="DE" term="%22BACILLUS+anthracis%22">BACILLUS anthracis</searchLink><br /><searchLink fieldCode="DE" term="%22BACILLUS+%28Bacteria%29%22">BACILLUS (Bacteria)</searchLink><br /><searchLink fieldCode="DE" term="%22MOLECULAR+biology%22">MOLECULAR biology</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Here we describe the characterization of a lipoprotein previously proposed as a potential Bacillus anthracis virulence determinant and vaccine candidate. This protein, designated MntA, is the solute-binding component of a manganese ion ATP-binding cassette transporter. Coupled proteomic-serological screen of a fully virulent wild-type B. anthracis Vollum strain, confirmed that MntA is expressed both in vitro and during infection. Expression of MntA is shown to be independent of the virulence plasmids pXO1 and pXO2. An mntA deletion, generated by allelic replacement, results in complete loss of MntA expression and its phenotypic analysis revealed: (i) impaired growth in rich media, alleviated by manganese supplementation; (ii) increased sensitivity to oxidative stress; and (iii) delayed release from cultured macrophages. The Δ mntA mutant expresses the anthrax-associated classical virulence factors, lethal toxin and capsule, in vitro as well as in vivo, and yet the mutation resulted in severe attenuation; a 10<superscript>4</superscript>-fold drop in LD<subscript>50</subscript> in a guinea pig model. MntA expressed in trans allowed to restore, almost completely, the virulence of the Δ mntA B. anthracis strain. We propose that MntA is a novel B. anthracis virulence determinant essential for the development of anthrax disease, and that B. anthracisΔ mntA strains have the potential to serve as platform for future live attenuated vaccines. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Molecular Microbiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1111/j.1365-2958.2005.04848.x
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      – Code: eng
        Text: English
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      Pagination:
        PageCount: 19
        StartPage: 533
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      – SubjectFull: ATP-binding cassette transporters
        Type: general
      – SubjectFull: CARRIER proteins
        Type: general
      – SubjectFull: MEMBRANE proteins
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      – SubjectFull: BIOLOGICAL membranes
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      – SubjectFull: PROTEINS
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      – SubjectFull: BACILLUS anthracis
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      – SubjectFull: BACILLUS (Bacteria)
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      – SubjectFull: MOLECULAR biology
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      – TitleFull: The solute-binding component of a putative Mn(II) ABC transporter (MntA) is a novel Bacillus anthracis virulence determinant.
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              Text: Oct2005
              Type: published
              Y: 2005
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