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Transcriptional profiling of murine organ genes in response to infection with Bacillus anthracis Ames spores.

ABSTRACT: Bacillus anthracis is the Gram-positive, spore-forming etiological agent of anthrax, an affliction studied because of its importance as a potential bioweapon. Although in vitro transcriptional responses of macrophages to either spore or anthrax toxins have been previously reported, little is known regarding the impact of infection on gene expression in host tissues. We infected Swiss-Webster mice intranasally with 5 LD(50) of B. anthracis-virulent Ames spores and observed the global transcriptional profiles of various tissues over a 48 h time period. RNA was extracted from spleen, lung, and heart tissues of infected and control mice and examined by Affymetrix GeneChip analysis. Approximately 580 host genes were significantly over or under expressed among the lung, spleen, and heart tissues at 8 and 48 h time points. Expression of genes encoding for surfactant and major histocompatibility complex (MHC) presentation was diminished during the early phase of infection in lungs. By 48 h, a significant number of genes were modulated in the heart, including up-regulation of calcium-binding-related gene expression, and down-regulation of multiple genes related to cell adhesion, formation of the extracellular matrix, and the cell cytoskeleton. Interestingly, the spleen 8h post-infection showed striking increases in the expression of genes that encode hydrolytic enzymes, and these levels remained elevated throughout infection. Further, genes involving antigen presentation and interferon responses were down-regulated in the spleen at 8 h. In late stages of infection, splenic genes related to the inflammatory response were up-regulated. This study is the first to describe the in vivo global transcriptional response of multiple organs during inhalational anthrax. Although numerous genes related to the host immunological response and certain protection mechanisms were up-regulated in these organs, a vast list of genes important for fully developing and maintaining this response were decreased. Additionally, the lung, spleen, and heart showed differential responses to the infection, further validating the demand for a better understanding of anthrax pathogenesis in order to design therapies against novel targets.

SUBMITTER: Moen ST

PROVIDER: S-EPMC2408921 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Transcriptional profiling of murine organ genes in response to infection with Bacillus anthracis Ames spores.

Moen Scott T ST Yeager Linsey A LA Lawrence William S WS Ponce Cindy C Galindo Cristi L CL Garner Harold R HR Baze Wallace B WB Suarez Giovanni G Peterson Johnny W JW Chopra Ashok K AK

Microbial pathogenesis 20071023 4

Bacillus anthracis is the Gram-positive, spore-forming etiological agent of anthrax, an affliction studied because of its importance as a potential bioweapon. Although in vitro transcriptional responses of macrophages to either spore or anthrax toxins have been previously reported, little is known regarding the impact of infection on gene expression in host tissues. We infected Swiss-Webster mice intranasally with 5 LD(50) of B. anthracis-virulent Ames spores and observed the global transcriptio ...[more]

PMID: 18037264

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Project description:BACKGROUND:Anthrax is an endemic disease that persists in the rural regions of China. The global genetic population structure of B.anthracis has also been defined by the canonical single-nucleotide polymorphisms (canSNP) and multiple-locus variable-number tandem repeat analysis (MLVA). Five canSNP lineages were found in China, and the A.Br.Ames lineage has been the second predominant group in recent years in China. The objective of this study was to reveal genetic diversity of the Ames lineage strains by MLVA. METHODS:Two molecular typing methods, canSNP and MLVA with 15markers were used to study the genetic relationship among the Ames lineage strains. The outbreak information associated with these strains was also collected and investigated. RESULTS:From 2007 to 2018, a total of 21 human anthrax infection outbreaks (68 patients) associated with B. anthracis Ames lineage strains were reported in China. Ames lineage strain-associated human anthrax is mainly distributed in the northern part of China, including the provinces of Inner Mongolia, Liaoning, Gansu, and Xinjiang. In the study, a total of 30 Ames lineage strains were included and 10 MLVA15 genotypes were identified. These strains were mainly found in northeast China, Inner Mongolia and Liaoning. In recent years, the Ames lineage strains were isolated in the two provinces every year. The 18 Ames lineage strains isolated from Inner Mongolia were divided into eight MLVA15 genotypes. From 2010 to 2015, there were continuous reports of outbreaks in Keyouzhongqi County, Inner Mongolia, and the strains that were isolated annually in succession belonged to the MLVA15-30 genotype. CONCLUSIONS:The Ames lineage strains are widely distributed in northern China. Their genetic diversity can be illustrated by the results of the MLVA. The genetic characteristics of the Ames lineage strains from outbreaks in different provinces varied. In some areas, human anthrax outbreaks occurred annually in succession, and these related strains grouped together. These observations indicate that the local environment was persistently contaminated with B. anthracis spores, vaccination of livestock should become the fundamental control measure in the areas.

Dataset Information

Transcriptional profiling of murine organ genes in response to infection with Bacillus anthracis Ames spores.

Publications

Transcriptional profiling of murine organ genes in response to infection with Bacillus anthracis Ames spores.

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