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In silico characterisation of stand-alone response regulators of Streptococcus pyogenes
Journal article   Open access   Peer reviewed

In silico characterisation of stand-alone response regulators of Streptococcus pyogenes

Sean J Buckley, Mark R Davies and David J McMillan
PLoS One, Vol.15(10), pp.1-28
2020
PMCID: PMC7571705
PMID: 33075055
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In silico characterisation of stand-alone response regulators of Streptococcus pyogenes5.23 MBDownloadView
Published Version Open Access CC BY V4.0
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https://doi.org/10.1371/journal.pone.0240834View
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Abstract

Regulators Recombination Transcription Virulence Metadata Infections Genomes Nucleotides Kinases Fibronectin Clinical outcomes Virulence factors Phylogenetics Deoxyribonucleic acid--DNA Binding Antigens RNA polymerase Gene expression Loci Switching Streptococcus Collagen Microenvironments Mutation Binding sites Polymorphism
Bacterial “stand-alone” response regulators (RRs) are pivotal to the control of gene transcription in response to changing cytosolic and extracellular microenvironments during infection. The genome of group A Streptococcus (GAS) encodes more than 30 stand-alone RRs that orchestrate the expression of virulence factors involved in infecting multiple tissues, so causing an array of potentially lethal human diseases. Here, we analysed the molecular epidemiology and biological associations in the coding sequences (CDSs) and upstream intergenic regions (IGRs) of 35 stand-alone RRs from a collection of global GAS genomes. Of the 944 genomes analysed, 97% encoded 32 or more of the 35 tested RRs. The length of RR CDSs ranged from 297 to 1587 nucleotides with an average nucleotide diversity (π) of 0.012, while the IGRs ranged from 51 to 666 nucleotides with average π of 0.017. We present new evidence of recombination in multiple RRs including mga, leading to mga-2 switching, emm-switching and emm-like gene chimerization, and the first instance of an isolate that encodes both mga-1 and mga-2. Recombination was also evident in rofA/nra and msmR loci with 15 emm-types represented in multiple FCT (fibronectin-binding, collagen-binding, T-antigen)-types, including novel emm-type/FCT-type pairings. Strong associations were observed between concatenated RR allele types, and emm-type, MLST-type, core genome phylogroup, and country of sampling. No strong associations were observed between individual loci and disease outcome. We propose that 11 RRs may form part of future refinement of GAS typing systems that reflect core genome evolutionary associations. This subgenomic analysis revealed allelic traits that were informative to the biological function, GAS strain definition, and regional outbreak detection.

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