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Homologous recombination between tandem paralogues drives evolution of a subset of type VII secretion system immunity genes in firmicute bacteria

Lookup NU author(s): Stephen Garrett, Dr Giusy MarianoORCiD, Professor Tracy Palmer FRS FRSE FMedSciORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


The type VII secretion system (T7SS) is found in many Gram-positive firmicutes and secretes protein toxins that mediate bacterial antagonism. Two T7SS toxins have been identified in Staphylococcus aureus, EsaD a nuclease toxin that is counteracted by the EsaG immunity protein, and TspA, which has membrane depolarising activity and is neutralised by TsaI. Both toxins are polymorphic, and strings of non-identical esaG and tsaI immunity genes are encoded in all S. aureus strains. To investigate the evolution of esaG repertoires, we analysed the sequences of the tandem esaG genes and their encoded proteins. We identified three blocks of high sequence similarity shared by all esaG genes and identified evidence of extensive recombination events between esaG paralogues facilitated through these conserved sequence blocks. Recombination between these blocks accounts for loss and expansion of esaG genes in S. aureus genomes and we identified evidence of such events during evolution of strains in clonal complex 8. TipC, an immunity protein for the TelC lipid II phosphatase toxin secreted by the streptococcal T7SS, is also encoded by multiple gene paralogues. Two blocks of high sequence similarity locate to the 5' and 3' end of tipC genes, and we found strong evidence for recombination between tipC paralogues encoded by Streptococcus mitis BCC08. By contrast, we found only a single homology block across tsaI genes, and little evidence for intergenic recombination within this gene family. We conclude that homologous recombination is one of the drivers for the evolution of T7SS immunity gene clusters.

Publication metadata

Author(s): Garrett SR, Mariano G, Dicks J, Palmer T

Publication type: Article

Publication status: Published

Journal: Microbial Genomics

Year: 2022

Volume: 8

Issue: 8

Online publication date: 12/08/2022

Acceptance date: 21/06/2022

Date deposited: 05/09/2022

ISSN (electronic): 2057-5858

Publisher: Microbiology Society


DOI: 10.1099/mgen.0.000868

PubMed id: 35960642


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Funder referenceFunder name
218622/Z/19/ZWellcome Trust