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The effects of methionine acquisition and synthesis on streptococcus pneumoniae growth and virulence

AutorBasavanna, Shilpa; Yuste, José ; Brown, Jeremy S.
Fecha de publicación22-ene-2013
EditorPublic Library of Science
CitaciónPLoS ONE 8 (1): e49638
ResumenBacterial pathogens need to acquire nutrients from the host, but for many nutrients their importance during infection remain poorly understood. We have investigated the importance of methionine acquisition and synthesis for Streptococcus pneumoniae growth and virulence using strains with gene deletions affecting a putative methionine ABC transporter lipoprotein (Sp_0149, metQ) and/or methionine biosynthesis enzymes (Sp_0585 - Sp_0586, metE and metF). Immunoblot analysis confirmed MetQ was a lipoprotein and present in all S. pneumoniae strains investigated. However, vaccination with MetQ did not prevent fatal S. pneumoniae infection in mice despite stimulating a strong specific IgG response. Tryptophan fluorescence spectroscopy and isothermal titration calorimetry demonstrated that MetQ has both a high affinity and specificity for L-methionine with a KD of ,25 nM, and a DmetQ strain had reduced uptake of C14-methionine. Growth of the DmetQ/DmetEF strain was greatly impaired in chemically defined medium containing low concentrations of methionine and in blood but was partially restored by addition of high concentrations of exogenous methionine. Mixed infection models showed no attenuation of the DmetQ, DmetEF and DmetQ/DmetEF strains in their ability to colonise the mouse nasopharnyx. In a mouse model of systemic infection although significant infection was established in all mice, there were reduced spleen bacterial CFU after infection with the DmetQ/DmetEF strain compared to the wild-type strain. These data demonstrate that Sp_0149 encodes a high affinity methionine ABC transporter lipoprotein and that Sp_0585 – Sp_0586 are likely to be required for methionine synthesis. Although Sp_0149 and Sp_0585-Sp_0586 make a contribution towards full virulence, neither was essential for S. pneumoniae survival during infection.
Descripción14 p.-1 tab.-8 fig. Shilpa Basavanna et alt.
Versión del editorhttp://dx.doi.org/10.1371/journal.pone.0049638
URIhttp://hdl.handle.net/10261/109964
DOI10.1371/journal.pone.0049638
ISSN1932-6203
E-ISSN1932-6203
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