Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 5487 - 5498 |
| Number of pages | 12 |
| Journal | Journal of Bacteriology |
| Volume | 195 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - 2013 |
Cite this
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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 journal › Article › Research › peer-review
TY - JOUR
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
Y1 - 2013
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.
UR - http://www.ncbi.nlm.nih.gov/pubmed/24097950
U2 - 10.1128/JB.00718-13
DO - 10.1128/JB.00718-13
M3 - Article
VL - 195
SP - 5487
EP - 5498
JO - Journal of Bacteriology
JF - Journal of Bacteriology
SN - 0021-9193
IS - 24
ER -