Unknown,Transcriptomics,Genomics,Proteomics

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Comparative genomic analysis of 93 Bp strains using K96243 as the reference

ABSTRACT: Natural isolates of Burkholderia pseudomallei (Bp), the causative agent of melioidosis, are known to exhibit diverse phenotypic traits, suggesting significant intraspecies genetic heterogeneity. Using whole-genome Bp microarrays, we experimentally mapped patterns of large-scale genomic variation in 93 South East Asian clinical, environmental, and animal Bp isolates. 14% of the reference Bp K96243 genome was variably present across the strain panel, more than double previous estimates, and both hypothetical proteins and paralogous gene pairs (PGPs) were significantly over-represented in the set of strain-variable genes. Examining patterns of PGP retention and loss, we successfully sub-categorized the PGPs into non-redundant, functionally biased, and completely redundant classes. We then identified 20 novel regions (âislandsâ) variably present between strains previously missed by computational analysis. Three of these novel islands contained lipopolysaccharide (LPS) biosynthesis genes, and strains lacking one such LPS island demonstrated reduced virulence in mouse infection assays. Clinical isolates associated with human melioidosis were strongly associated with the presence of specific genomic islands, but a common set of virulence-related genes was present in all strains. Our results suggest that most Bp strains possess a core virulence machinery capable of causing disease, but accessory functions provided by mobile elements may predispose distinct host species and ecological niches to specific individual strains. This hierarchical model of Bp virulence reconciles previous conflicting studies comparing Bp environmental and clinical isolates, and suggests novel molecular strategies for disease surveillance and outbreak detection efforts in melioidosis. Keywords: aCGH of 93 Bp strains genomic DNA of 93 Bp strains were assessed on Bp_array_v2

ORGANISM(S): Burkholderia pseudomallei K96243

SUBMITTER: P Tan

PROVIDER: E-GEOD-9491 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The core and accessory genomes of Burkholderia pseudomallei: implications for human melioidosis.

Sim Siew Hoon SH Yu Yiting Y Lin Chi Ho CH Karuturi R Krishna M RK Wuthiekanun Vanaporn V Tuanyok Apichai A Chua Hui Hoon HH Ong Catherine C Paramalingam Sivalingam Suppiah SS Tan Gladys G Tang Lynn L Lau Gary G Ooi Eng Eong EE Woods Donald D Feil Edward E Peacock Sharon J SJ Tan Patrick P

PLoS pathogens 20081017 10

Natural isolates of Burkholderia pseudomallei (Bp), the causative agent of melioidosis, can exhibit significant ecological flexibility that is likely reflective of a dynamic genome. Using whole-genome Bp microarrays, we examined patterns of gene presence and absence across 94 South East Asian strains isolated from a variety of clinical, environmental, or animal sources. 86% of the Bp K96243 reference genome was common to all the strains representing the Bp "core genome", comprising genes largely ...[more]

PMID: 18927621

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Project description:Yunnan Province, China is thought to be the original source of biovar Orientalis of Yersinia pestis, the causative agent of the third plague pandemic that has spread globally since the end of the 19th century. Although encompassing a large area of natural plague foci, Y. pestis strains have rarely been found in live rodents during surveillance in Yunnan, and most isolates are from rodent corpses and their fleas. In 2017, 10 Y. pestis strains were isolated from seven live rodents and three fleas in Heqing County (HQ) of Yunnan. These strains were supposed to have low virulence to local rodents Eothenomys miletus and Apodemus chevrieri because the rodents were healthy and no dead animals were found in surrounding areas, as had occurred in previous epizootic disease. We performed microscopic and biochemical examinations of the isolates,and compared their whole-genome sequences and transcriptome with those of 10 high virulence Y. pestis strains that were isolated from the adjacent city (Lijiang). We analyzed the phenotypic, genomic, and transcriptomic characteristics of live rodent isolates. The isolates formed a previously undefined monophyletic branch of Y. pestis that was named 1.IN5. Six SNPs, two indels, and one copy number variation were detected between live rodent isolates and the high virulence neighbors. No obvious functional consequence of these variations was found according to the known annotation information. Among the genes that were differentially expressed between the live rodent isolates and their high virulence neighbors, we detected five iron transfer-related genes that were significantly up-regulated in live rodent isolates compared with high virulence isolates (|log2 (FC) | >1, p.adjust <0.05), indicating these genes may be related to the low-virulence phenotype. The novel genotype of Y. pestis reported here provides further insights into the evolution and spread of plague as well as clues that may help to decipher the virulence mechanism of this notorious pathogen.

Dataset Information

Comparative genomic analysis of 93 Bp strains using K96243 as the reference

Publications

The core and accessory genomes of Burkholderia pseudomallei: implications for human melioidosis.

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