Dataset Information

AB_SA: Accessory genes-Based Source Attribution - tracing the source of Salmonella enterica Typhimurium environmental strains.

ABSTRACT: The partitioning of pathogenic strains isolated in environmental or human cases to their sources is challenging. The pathogens usually colonize multiple animal hosts, including livestock, which contaminate the food-production chain and the environment (e.g. soil and water), posing an additional public-health burden and major challenges in the identification of the source. Genomic data opens up new opportunities for the development of statistical models aiming to indicate the likely source of pathogen contamination. Here, we propose a computationally fast and efficient multinomial logistic regression source-attribution classifier to predict the animal source of bacterial isolates based on 'source-enriched' loci extracted from the accessory-genome profiles of a pangenomic dataset. Depending on the accuracy of the model's self-attribution step, the modeller selects the number of candidate accessory genes that best fit the model for calculating the likelihood of (source) category membership. The Accessory genes-Based Source Attribution (AB_SA) method was applied to a dataset of strains of Salmonella enterica Typhimurium and its monophasic variant (S. enterica 1,4,[5],12:i:-). The model was trained on 69 strains with known animal-source categories (i.e. poultry, ruminant and pig). The AB_SA method helped to identify 8 genes as predictors among the 2802 accessory genes. The self-attribution accuracy was 80?%. The AB_SA model was then able to classify 25 of the 29 S. enterica Typhimurium and S. enterica 1,4,[5],12:i:- isolates collected from the environment (considered to be of unknown source) into a specific category (i.e. animal source), with more than 85?% of probability. The AB_SA method herein described provides a user-friendly and valuable tool for performing source-attribution studies in only a few steps. AB_SA is written in R and freely available at https://github.com/lguillier/AB_SA.

SUBMITTER: Guillier L

PROVIDER: S-EPMC7478624 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

AB_SA: Accessory genes-Based Source Attribution - tracing the source of <i>Salmonella enterica</i> Typhimurium environmental strains.

Guillier Laurent L Gourmelon Michèle M Lozach Solen S Cadel-Six Sabrina S Vignaud Marie-Léone ML Munck Nanna N Hald Tine T Palma Federica F

Microbial genomics 20200701 7

The partitioning of pathogenic strains isolated in environmental or human cases to their sources is challenging. The pathogens usually colonize multiple animal hosts, including livestock, which contaminate the food-production chain and the environment (e.g. soil and water), posing an additional public-health burden and major challenges in the identification of the source. Genomic data opens up new opportunities for the development of statistical models aiming to indicate the likely source of pat ...[more]

PMID: 32320376

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Project description:Microbial horizontal gene transfer is a continuous process that shapes bacterial genomic adaptation to the environment and the composition of concurrent microbial ecology. This includes the potential impact of synthetic antibiotic utilization in farm animal production on overall antibiotic resistance issues; however, the mechanisms behind the evolution of microbial communities are not fully understood. We explored potential mechanisms by experimentally examining the relatedness of phylogenetic inference between multidrug-resistant Salmonella enterica serovar Typhimurium isolates and pathogenic Salmonella Typhimurium strains based on genome-wide single-nucleotide polymorphism (SNP) comparisons. Antibiotic-resistant S Typhimurium isolates in a simulated farm environment barely lost their resistance, whereas sensitive S Typhimurium isolates in soils gradually acquired higher tetracycline resistance under antibiotic pressure and manipulated differential expression of antibiotic-resistant genes. The expeditious development of antibiotic resistance and the ensuing genetic alterations in antimicrobial resistance genes in S Typhimurium warrant effective actions to control the dissemination of Salmonella antibiotic resistance.IMPORTANCE Antibiotic resistance is attributed to the misuse or overuse of antibiotics in agriculture, and antibiotic resistance genes can also be transferred to bacteria under environmental stress. In this study, we report a unidirectional alteration in antibiotic resistance from susceptibility to increased resistance. Highly sensitive Salmonella enterica serovar Typhimurium isolates from organic farm systems quickly acquired tetracycline resistance under antibiotic pressure in simulated farm soil environments within 2 weeks, with expression of antibiotic resistance-related genes that was significantly upregulated. Conversely, originally resistant S Typhimurium isolates from conventional farm systems lost little of their resistance when transferred to environments without antibiotic pressure. Additionally, multidrug-resistant S Typhimurium isolates genetically shared relevancy with pathogenic S Typhimurium isolates, whereas susceptible isolates clustered with nonpathogenic strains. These results provide detailed discussion and explanation about the genetic alterations and simultaneous acquisition of antibiotic resistance in S Typhimurium in agricultural environments.

Project description:Penetration of intestinal epithelial cells by Salmonella enterica serovar Typhimurium requires the expression of invasion genes, found in Salmonella pathogenicity island 1 (SPI1), that encode components of a type III secretion apparatus. These genes are controlled in a complex manner by regulators within SPI1, including HilA and InvF, and those outside SPI1, such as the two-component regulators PhoP/PhoQ and BarA/SirA. We report here that epithelial cell invasion requires the serovar Typhimurium homologue of Escherichia coli csrA, which encodes a regulator that alters the stability of specific mRNA targets. A deletion mutant of csrA was unable to efficiently invade cultured epithelial cells and showed reduced expression of four tested SPI1 genes, hilA, invF, sipC, and prgH. Overexpression of csrA from an induced araBAD promoter also negatively affected the expression of these genes, indicating that CsrA can act as both a positive and a negative regulator of SPI1 genes and suggesting that the bacterium must tightly control the level or activity of CsrA to achieve maximal invasion. We found that CsrA affected hilA, a regulator of the other three genes we tested, probably by controlling one or more genetic elements that regulate hilA. We also found that both the loss and the overexpression of csrA reduced the expression of two regulators of hilA, hilC and hilD, suggesting that csrA exerts its control of hilA through one or both of these regulators. We further found, however, that CsrA could affect the expression of both invF and sipC independent of its effects on hilA. One additional striking phenotype of the csrA mutant, not observed in a comparable E. coli mutant, was its slow growth. Phenotypic revertants that had normal growth rates, while maintaining the csrA mutation, were common. These suppressed strains, however, did not recover the ability to invade cultured cells, indicating that the csrA-mediated loss of invasion cannot be attributed simply to poor growth and that the growth and invasion deficits of the csrA mutant arise from effects of CsrA on different targets.

Dataset Information

AB_SA: Accessory genes-Based Source Attribution - tracing the source of Salmonella enterica Typhimurium environmental strains.

Publications

AB_SA: Accessory genes-Based Source Attribution - tracing the source of <i>Salmonella enterica</i> Typhimurium environmental strains.

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