Characterization of the Burkholderia pseudomallei K96243 capsular polysaccharide I coding region

J. Cuccui; T.S. S. Milne; N. Harmer; A.J. J. George; S.V. V. Harding; R.E. E. Dean; A.E. E. Scott; Mitali Sarkar-Tyson; B.W. W. Wren; R.W. W. Titball; J.L. L. Prior

doi:10.1128/IAI.05805-11

Characterization of the Burkholderia pseudomallei K96243 capsular polysaccharide I coding region

J. Cuccui, T.S. S. Milne, N. Harmer, A.J. J. George, S.V. V. Harding, R.E. E. Dean, A.E. E. Scott, Mitali Sarkar-Tyson, B.W. W. Wren, R.W. W. Titball, J.L. L. Prior

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Abstract

Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic to regions of Southeast Asia and Northern Australia. Both humans and a range of other animal species are susceptible to melioidosis, and the production of a group 3 polysaccharide capsule in B. pseudomallei is essential for virulence. B. pseudomallei capsular polysaccharide (CPS) I comprises unbranched manno-heptopyranose residues and is encoded by a 34.5-kb locus on chromosome 1. Despite the importance of this locus, the role of all of the genes within this region is unclear. We inactivated 18 of these genes and analyzed their phenotype using Western blotting and immunofluorescence staining. Furthermore, by combining this approach with bioinformatic analysis, we were able to develop a model for CPS I biosynthesis and export. We report that inactivating gmhA, wcbJ, and wcbN in B. pseudomallei K96243 retains the immunogenic integrity of the polysaccharide despite causing attenuation in the BALB/c murine infection model. Mice immunized with the B. pseudomallei K96243 mutants lacking a functional copy of either gmhA or wcbJ were afforded significant levels of protection against a wild-type B. pseudomallei K96243 challenge. © 2012, American Society for Microbiology.

Original language	English
Pages (from-to)	1209-1221
Number of pages	13
Journal	Infection and Immunity
Volume	80
Issue number	3
DOIs	https://doi.org/10.1128/IAI.05805-11
Publication status	Published - 2012
Externally published	Yes

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title = "Characterization of the Burkholderia pseudomallei K96243 capsular polysaccharide I coding region",

abstract = "Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic to regions of Southeast Asia and Northern Australia. Both humans and a range of other animal species are susceptible to melioidosis, and the production of a group 3 polysaccharide capsule in B. pseudomallei is essential for virulence. B. pseudomallei capsular polysaccharide (CPS) I comprises unbranched manno-heptopyranose residues and is encoded by a 34.5-kb locus on chromosome 1. Despite the importance of this locus, the role of all of the genes within this region is unclear. We inactivated 18 of these genes and analyzed their phenotype using Western blotting and immunofluorescence staining. Furthermore, by combining this approach with bioinformatic analysis, we were able to develop a model for CPS I biosynthesis and export. We report that inactivating gmhA, wcbJ, and wcbN in B. pseudomallei K96243 retains the immunogenic integrity of the polysaccharide despite causing attenuation in the BALB/c murine infection model. Mice immunized with the B. pseudomallei K96243 mutants lacking a functional copy of either gmhA or wcbJ were afforded significant levels of protection against a wild-type B. pseudomallei K96243 challenge. {\textcopyright} 2012, American Society for Microbiology.",

author = "J. Cuccui and Milne, {T.S. S.} and N. Harmer and George, {A.J. J.} and Harding, {S.V. V.} and Dean, {R.E. E.} and Scott, {A.E. E.} and Mitali Sarkar-Tyson and Wren, {B.W. W.} and Titball, {R.W. W.} and Prior, {J.L. L.}",

year = "2012",

doi = "10.1128/IAI.05805-11",

language = "English",

volume = "80",

pages = "1209--1221",

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TY - JOUR

T1 - Characterization of the Burkholderia pseudomallei K96243 capsular polysaccharide I coding region

AU - Cuccui, J.

AU - Milne, T.S. S.

AU - Harmer, N.

AU - George, A.J. J.

AU - Harding, S.V. V.

AU - Dean, R.E. E.

AU - Scott, A.E. E.

AU - Sarkar-Tyson, Mitali

AU - Wren, B.W. W.

AU - Titball, R.W. W.

AU - Prior, J.L. L.

PY - 2012

Y1 - 2012

N2 - Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic to regions of Southeast Asia and Northern Australia. Both humans and a range of other animal species are susceptible to melioidosis, and the production of a group 3 polysaccharide capsule in B. pseudomallei is essential for virulence. B. pseudomallei capsular polysaccharide (CPS) I comprises unbranched manno-heptopyranose residues and is encoded by a 34.5-kb locus on chromosome 1. Despite the importance of this locus, the role of all of the genes within this region is unclear. We inactivated 18 of these genes and analyzed their phenotype using Western blotting and immunofluorescence staining. Furthermore, by combining this approach with bioinformatic analysis, we were able to develop a model for CPS I biosynthesis and export. We report that inactivating gmhA, wcbJ, and wcbN in B. pseudomallei K96243 retains the immunogenic integrity of the polysaccharide despite causing attenuation in the BALB/c murine infection model. Mice immunized with the B. pseudomallei K96243 mutants lacking a functional copy of either gmhA or wcbJ were afforded significant levels of protection against a wild-type B. pseudomallei K96243 challenge. © 2012, American Society for Microbiology.

AB - Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic to regions of Southeast Asia and Northern Australia. Both humans and a range of other animal species are susceptible to melioidosis, and the production of a group 3 polysaccharide capsule in B. pseudomallei is essential for virulence. B. pseudomallei capsular polysaccharide (CPS) I comprises unbranched manno-heptopyranose residues and is encoded by a 34.5-kb locus on chromosome 1. Despite the importance of this locus, the role of all of the genes within this region is unclear. We inactivated 18 of these genes and analyzed their phenotype using Western blotting and immunofluorescence staining. Furthermore, by combining this approach with bioinformatic analysis, we were able to develop a model for CPS I biosynthesis and export. We report that inactivating gmhA, wcbJ, and wcbN in B. pseudomallei K96243 retains the immunogenic integrity of the polysaccharide despite causing attenuation in the BALB/c murine infection model. Mice immunized with the B. pseudomallei K96243 mutants lacking a functional copy of either gmhA or wcbJ were afforded significant levels of protection against a wild-type B. pseudomallei K96243 challenge. © 2012, American Society for Microbiology.

U2 - 10.1128/IAI.05805-11

DO - 10.1128/IAI.05805-11

M3 - Article

SN - 0019-9567

VL - 80

SP - 1209

EP - 1221

JO - Infection and Immunity

JF - Infection and Immunity

IS - 3

ER -

Characterization of the Burkholderia pseudomallei K96243 capsular polysaccharide I coding region

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