Evolutionary analysis of Burkholderia pseudomallei identifies putative novel virulence genes, including a microbial regulator of host cell autophagy

Arvind P Singh, Shu-chin Lai, Tannistha Nandi, Hui Hoon Chua, Wen Fong Ooi, Catherine Ong, John Dallas Boyce, Ben Adler, Rodney James Devenish, Patrick Tan

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Burkholderia pseudomallei (Bp), the causative agent of melioidosis contains a large pathogen genome (7.2 Mb) with approximately 2000 genes of putative or unknown function. Interactions with potential hosts and environmental factors may induce rapid adaptations in these Bp genes, which can be discerned through evolutionary analysis of multiple Bp genomes. Here, we show that several previously-uncharacterized Bp genes bearing genetic signatures of rapid adaptation (positive selection) can induce diverse cellular phenotypes when expressed in mammalian cells. Notably, several of these phenotypes are plausibly related to virulence, including multi-nuclear giant cell formation, apoptosis, and autophagy induction. Specifically, we show that BPSS0180, a Type VI cluster-associated gene, is capable of inducing autophagy in both phagocytic and non-phagocytic mammalian cells. Following infection of macrophage cells, a Bp mutant disrupted in BPSS0180 exhibited significantly decreased colocalization with LC3 and impaired intracellular survival; these phenotypes were rescued by introduction of an intact BPSS0180 gene. The results suggest that BPSS0180 may be a novel inducer of host cell autophagy that contributes to Bp intracellular growth. More generally, our study highlights the utility of applying evolutionary principles to microbial genomes to identify novel virulence genes.
Original languageEnglish
Pages (from-to)5487 - 5498
Number of pages12
JournalJournal of Bacteriology
Volume195
Issue number24
DOIs
Publication statusPublished - 2013

Cite this

Singh, Arvind P ; Lai, Shu-chin ; Nandi, Tannistha ; Chua, Hui Hoon ; Ooi, Wen Fong ; Ong, Catherine ; Boyce, John Dallas ; Adler, Ben ; Devenish, Rodney James ; Tan, Patrick. / Evolutionary analysis of Burkholderia pseudomallei identifies putative novel virulence genes, including a microbial regulator of host cell autophagy. In: Journal of Bacteriology. 2013 ; Vol. 195, No. 24. pp. 5487 - 5498.
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title = "Evolutionary analysis of Burkholderia pseudomallei identifies putative novel virulence genes, including a microbial regulator of host cell autophagy",
abstract = "Burkholderia pseudomallei (Bp), the causative agent of melioidosis contains a large pathogen genome (7.2 Mb) with approximately 2000 genes of putative or unknown function. Interactions with potential hosts and environmental factors may induce rapid adaptations in these Bp genes, which can be discerned through evolutionary analysis of multiple Bp genomes. Here, we show that several previously-uncharacterized Bp genes bearing genetic signatures of rapid adaptation (positive selection) can induce diverse cellular phenotypes when expressed in mammalian cells. Notably, several of these phenotypes are plausibly related to virulence, including multi-nuclear giant cell formation, apoptosis, and autophagy induction. Specifically, we show that BPSS0180, a Type VI cluster-associated gene, is capable of inducing autophagy in both phagocytic and non-phagocytic mammalian cells. Following infection of macrophage cells, a Bp mutant disrupted in BPSS0180 exhibited significantly decreased colocalization with LC3 and impaired intracellular survival; these phenotypes were rescued by introduction of an intact BPSS0180 gene. The results suggest that BPSS0180 may be a novel inducer of host cell autophagy that contributes to Bp intracellular growth. More generally, our study highlights the utility of applying evolutionary principles to microbial genomes to identify novel virulence genes.",
author = "Singh, {Arvind P} and Shu-chin Lai and Tannistha Nandi and Chua, {Hui Hoon} and Ooi, {Wen Fong} and Catherine Ong and Boyce, {John Dallas} and Ben Adler and Devenish, {Rodney James} and Patrick Tan",
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Evolutionary analysis of Burkholderia pseudomallei identifies putative novel virulence genes, including a microbial regulator of host cell autophagy. / Singh, Arvind P; Lai, Shu-chin; Nandi, Tannistha; Chua, Hui Hoon; Ooi, Wen Fong; Ong, Catherine; Boyce, John Dallas; Adler, Ben; Devenish, Rodney James; Tan, Patrick.

In: Journal of Bacteriology, Vol. 195, No. 24, 2013, p. 5487 - 5498.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Evolutionary analysis of Burkholderia pseudomallei identifies putative novel virulence genes, including a microbial regulator of host cell autophagy

AU - Singh, Arvind P

AU - Lai, Shu-chin

AU - Nandi, Tannistha

AU - Chua, Hui Hoon

AU - Ooi, Wen Fong

AU - Ong, Catherine

AU - Boyce, John Dallas

AU - Adler, Ben

AU - Devenish, Rodney James

AU - Tan, Patrick

PY - 2013

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N2 - Burkholderia pseudomallei (Bp), the causative agent of melioidosis contains a large pathogen genome (7.2 Mb) with approximately 2000 genes of putative or unknown function. Interactions with potential hosts and environmental factors may induce rapid adaptations in these Bp genes, which can be discerned through evolutionary analysis of multiple Bp genomes. Here, we show that several previously-uncharacterized Bp genes bearing genetic signatures of rapid adaptation (positive selection) can induce diverse cellular phenotypes when expressed in mammalian cells. Notably, several of these phenotypes are plausibly related to virulence, including multi-nuclear giant cell formation, apoptosis, and autophagy induction. Specifically, we show that BPSS0180, a Type VI cluster-associated gene, is capable of inducing autophagy in both phagocytic and non-phagocytic mammalian cells. Following infection of macrophage cells, a Bp mutant disrupted in BPSS0180 exhibited significantly decreased colocalization with LC3 and impaired intracellular survival; these phenotypes were rescued by introduction of an intact BPSS0180 gene. The results suggest that BPSS0180 may be a novel inducer of host cell autophagy that contributes to Bp intracellular growth. More generally, our study highlights the utility of applying evolutionary principles to microbial genomes to identify novel virulence genes.

AB - Burkholderia pseudomallei (Bp), the causative agent of melioidosis contains a large pathogen genome (7.2 Mb) with approximately 2000 genes of putative or unknown function. Interactions with potential hosts and environmental factors may induce rapid adaptations in these Bp genes, which can be discerned through evolutionary analysis of multiple Bp genomes. Here, we show that several previously-uncharacterized Bp genes bearing genetic signatures of rapid adaptation (positive selection) can induce diverse cellular phenotypes when expressed in mammalian cells. Notably, several of these phenotypes are plausibly related to virulence, including multi-nuclear giant cell formation, apoptosis, and autophagy induction. Specifically, we show that BPSS0180, a Type VI cluster-associated gene, is capable of inducing autophagy in both phagocytic and non-phagocytic mammalian cells. Following infection of macrophage cells, a Bp mutant disrupted in BPSS0180 exhibited significantly decreased colocalization with LC3 and impaired intracellular survival; these phenotypes were rescued by introduction of an intact BPSS0180 gene. The results suggest that BPSS0180 may be a novel inducer of host cell autophagy that contributes to Bp intracellular growth. More generally, our study highlights the utility of applying evolutionary principles to microbial genomes to identify novel virulence genes.

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