Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis.

Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacterial populations remain poorly understood. We sequenced the genomes of 2,101 emm28 S. pyogenes invasive strains, from which we selected 492 phylogenetically diverse strains for transcriptome analysis and 50 strains for virulence assessment. Data integration provided a novel understanding of the virulence mechanisms of this model organism. Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens.

Antibacterial Susceptibilities of Escherichia coli from Community-Acquired Urinary Tract Infections in the Faroe Islands, Associations with Antibacterial Sales, and Comparison with Iceland and Denmark.

Currently, data on Escherichia coli antibacterial susceptibilities in the Faroe Islands are lacking. The aim was to investigate the antibacterial susceptibilities of E. coli from patients with community-acquired urinary tract infections in the Faroe Islands, correlate with antibacterial sales, and compare with Iceland and Denmark. From 2009 to 2010 and in 2012, 12 general practitioners from the Faroe Islands were recruited to provide urine samples from patients. Antibacterial susceptibilities were determined by disc diffusion testing according to the Clinical and Laboratory Standards Institute methods and criteria. Logistic regression (quasibinomial) of the antibacterial resistance proportions versus mean sales during the period of 2008-2011 was used to determine association. Nonsusceptibility to at least 1 of the 14 antibacterial drugs investigated was found in 54% of the E. coli isolates and was most common to ampicillin (46%), followed by sulfamethoxazole (39%), trimethoprim (27%), trimethoprim/sulfamethoxazole (27%), and <10% to the remaining 10 antibiotics. The resistance prevalence did not change significantly with time. From logistic regression modeling, we find significant associations between antibacterial mean sales and antibacterial resistances. For the resistances in the Faroe Islands compared with data from Denmark and Iceland, we infer two groups of resistances indicating different responses-one steep and one gradual-to antibacterial sales. For these two groups, we find ß1 = 4.77 (Std. Error = 0.624, p-value = 0.002) and ß1 = 0.26 (Std. Error = 0.020, p-value = 4e-7) for the steep and gradual groups, respectively. This knowledge can potentially be used to predict and control the future increase in E. coli resistance with antibacterial sales.

Antibacterial use in the Faroe Islands, Iceland, and Denmark 1999-2011.

BACKGROUND: The Faroe Islands, Iceland, and Denmark are neighbouring Nordic countries with great ethnic, cultural, and political similarities and are relatively homogeneous. Important information about prescribing practices can be obtained by comparing the antibacterial use in these countries. The objective was to describe, compare, and analyse the use of systemic antibacterial agents in these countries during the y 1999-2011. METHODS: Data were obtained from the Faroe Islands, Iceland, and Denmark on systemic antibacterial use and expressed in defined daily dosages (DDD). Prescription data were also obtained for specific age groups. RESULTS: The total antibacterial use for the y 1999-2011 varied markedly between the 3 countries, with a mean use of 21.8 DDD/1000 inhabitants/day (DID) in Iceland, 17.7 in the Faroe Islands, and 16.3 in Denmark. The total use remained fairly constant over the years in the Faroe Islands and Iceland, whereas in Denmark it increased gradually from 13.5 DID in 1999 to 19.5 DID in 2011. The higher use in Iceland can be explained by much higher consumption of tetracyclines. There was also considerable variation in the use of individual penicillins and macrolides between the countries. CONCLUSIONS: Despite the great ethnic and cultural similarities of these 3 countries, we found marked differences in total antibacterial use and important differences in the use of individual antibacterials.