Dataset Information

Genomic Epidemiology and Antimicrobial Resistance Mechanisms of Imported Typhoid in Australia.

ABSTRACT: Typhoid fever is an invasive bacterial disease of humans that disproportionately affects low- and middle-income countries. Antimicrobial resistance (AMR) has been increasingly prevalent in recent decades in Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, limiting treatment options. In Australia, most cases of typhoid fever are imported due to travel to regions where typhoid fever is endemic. Here, all 116 isolates of S. Typhi isolated in Victoria, Australia, between 1 July 2018 and 30 June 2020, underwent whole-genome sequencing and antimicrobial susceptibility testing. Genomic data were linked to international travel data collected from routine case interviews. Travel to South Asia accounted for most cases, with 92.2% imported from seven primary countries (the top two were India, n = 87, and Pakistan, n = 12). A total of 17 S. Typhi genotypes were detected in the 2-year cohort, with 48.2% genotyped as part of global AMR lineages. Ciprofloxacin resistance was detected in two lineages, 3.3 and 4.3.1.2, all from cases with reported travel to India. Nearly all multidrug and extensively drug resistant isolates (90%) were from cases with reported travel to Pakistan in genotypes 4.3.1.1 and 4.3.1.1.P1. Extended spectrum beta-lactamases, blaCTX-M-15 and blaSHV-12, were detected in cases with travel to Pakistan and India, respectively. Linking epidemiological data with genomic studies of S. Typhi provides an opportunity to improve understanding of the emergence, spread and risk of drug-resistant S. Typhi infections and to better inform empirical treatment guidelines in returned travelers.

SUBMITTER: Ingle DJ

PROVIDER: S-EPMC8597785 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Genomic Epidemiology and Antimicrobial Resistance Mechanisms of Imported Typhoid in Australia.

Ingle Danielle J DJ Andersson Patiyan P Valcanis Mary M Wilmot Mathilda M Easton Marion M Lane Courtney C Barden Jessica J Gonçalves da Silva Anders A Seemann Torsten T Horan Kristy K Ballard Susan A SA Sherry Norelle L NL Williamson Deborah A DA Howden Benjamin P BP

Antimicrobial agents and chemotherapy 20210920 12

Typhoid fever is an invasive bacterial disease of humans that disproportionately affects low- and middle-income countries. Antimicrobial resistance (AMR) has been increasingly prevalent in recent decades in Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, limiting treatment options. In Australia, most cases of typhoid fever are imported due to travel to regions where typhoid fever is endemic. Here, all 116 isolates of S. Typhi isolated in Victoria, Australia, b ...[more]

PMID: 34543095

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Project description:Salmonella enterica serovar Gallinarum causes devastating outbreaks of fowl typhoid across the globe, especially in developing countries. With the use of antimicrobial agents being reduced due to legislation and the absence of licensed vaccines in some parts of the world, an attractive complementary control strategy is to breed chickens for increased resistance to Salmonella. The potential for genetic control of salmonellosis has been demonstrated by experimental challenge of inbred populations. Quantitative trait loci (QTL) associated with resistance have been identified in many genomic regions. A major QTL associated with systemic salmonellosis has been identified in a region termed SAL1. In the present study, two outbreaks of fowl typhoid in 2007 and 2012 in the United Kingdom were used to investigate the genetic architecture of Salmonella resistance in commercial laying hens. In the first outbreak 100 resistant and 150 susceptible layers were genotyped using 11 single nucleotide polymorphism (SNP) and 3 microsatellite markers located in the previously identified SAL1 region on chromosome 5. From the second outbreak 100 resistant and 200 susceptible layers, belonging to a different line, were genotyped with a high-density (600 K) genome-wide SNP array. Substantial heritability estimates were obtained in both populations (h 2 = 0.22 and 0.26, for the layers in the first and second outbreak, respectively). Significant associations with three markers on chromosome 5 located close to AKT1 and SIVA1 genes, coding for RAC-alpha serine/threonine protein kinase, and the CD27-binding protein SIVA1, respectively, were identified in the first outbreak. From analysis of the second outbreak, eight genome-wide significant associations with Salmonella resistance were identified on chromosomes 1, 6, 7, 11, 23, 24, 26, 28 and several others with suggestive genome-wide significance were found. Pathway and network analysis revealed the presence of many innate immune pathways related to Salmonella resistance. Although, significant associations with SNPs located in the SAL1 locus were not identified by the genome-wide scan for layers from the second outbreak, pathway analysis revealed P13K/AKT signaling as the most significant pathway. In summary, resistance to fowl typhoid is a heritable polygenic trait that could possibly be enhanced through selective breeding.

Dataset Information

Genomic Epidemiology and Antimicrobial Resistance Mechanisms of Imported Typhoid in Australia.

Publications

Genomic Epidemiology and Antimicrobial Resistance Mechanisms of Imported Typhoid in Australia.

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