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In silico characterisation of the two-component system regulators of Streptococcus pyogenes.

ABSTRACT: Bacteria respond to environmental changes through the co-ordinated regulation of gene expression, often mediated by two-component regulatory systems (TCS). Group A Streptococcus (GAS), a bacterium which infects multiple human body sites and causes multiple diseases, possesses up to 14 TCS. In this study we examined genetic variation in the coding sequences and non-coding DNA upstream of these TCS as a method for evaluating relationships between different GAS emm-types, and potential associations with GAS disease. Twelve of the 14 TCS were present in 90% of the genomes examined. The length of the intergenic regions (IGRs) upstream of TCS coding regions varied from 39 to 345 nucleotides, with an average nucleotide diversity of 0.0064. Overall, IGR allelic variation was generally conserved with an emm-type. Subsequent phylogenetic analysis of concatenated sequences based on all TCS IGR sequences grouped genomes of the same emm-type together. However grouping with emm-pattern and emm-cluster-types was much weaker, suggesting epidemiological and functional properties associated with the latter are not due to evolutionary relatedness of emm-types. All emm5, emm6 and most of the emm18 genomes, all historically considered rheumatogenic emm-types clustered together, suggesting a shared evolutionary history. However emm1, emm3 and several emm18 genomes did not cluster within this group. These latter emm18 isolates were epidemiologically distinct from other emm18 genomes in study, providing evidence for local variation. emm-types associated with invasive disease or nephritogenicity also did not cluster together. Considering the TCS coding sequences (cds), correlation with emm-type was weaker than for the IGRs, and no strong correlation with disease was observed. Deletion of the malate transporter, maeP, was identified that serves as a putative marker for the emm89.0 subtype, which has been implicated in invasive outbreaks. A recombination-related, subclade-forming DNA motif was identified in the putative receiver domain of the Spy1556 response regulator that correlated with throat-associated emm-pattern-type A-C strains.

SUBMITTER: Buckley SJ

PROVIDER: S-EPMC6013163 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:UnlabelledTwo-component systems (TCSs) are regulatory systems in bacteria that play important roles in sensing and adapting to the environment. In this study, we systematically evaluated the roles of TCSs in the susceptibility of the group A Streptococcus (GAS; Streptococcus pyogenes) SF370 strain to several types of lantibiotics. Using individual TCS deletion mutants, we found that the deletion of srtRK (spy_1081-spy_1082) in SF370 increased the susceptibility to nisin A, which is produced by Lactococcus lactis ATCC 11454, but susceptibility to other types of lantibiotics (nukacin ISK-1, produced by Staphylococcus warneri, and staphylococcin C55, produced by Staphylococcus aureus) was not altered in the TCS mutants tested. The expression of srtFEG (spy_1085 to spy_1087), which is located downstream of srtRK and is homologous to ABC transporters, was increased in response to nisin A. However, srtEFG expression was not induced by nisin A in the srtRK mutant. The inactivation of srtFEG increased the susceptibility to nisin A. These results suggest that SrtRK controls SrtFEG expression to alter the susceptibility to nisin A. Further experiments showed that SrtRK is required for coexistence with L. lactis ATCC 11454, which produces nisin A. Our results elucidate the important roles of S. pyogenes TCSs in the interactions between different bacterial species, including bacteriocin-producing bacteria.ImportanceIn this study, we focused on the association of TCSs with susceptibility to bacteriocins in S. pyogenes SF370, which has no ability to produce bacteriocins, and reported two major new findings. We demonstrated that the SrtRK TCS is related to susceptibility to nisin A by controlling the ABC transporter SrtFEG. We also showed that S. pyogenes SrtRK is important for survival when the bacteria are cocultured with nisin A-producing Lactococcus lactis This report highlights the roles of TCSs in the colocalization of bacteriocin-producing bacteria and non-bacteriocin-producing bacteria. Our findings provide new insights into the function of TCSs in S. pyogenes.

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In silico characterisation of the two-component system regulators of Streptococcus pyogenes.

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