csrT Represents a New Class of csrA-Like Regulatory Genes Associated with Integrative Conjugative Elements of Legionella pneumophila

Bacterial evolution is accelerated by mobile genetic elements. To spread horizontally and to benefit the recipient bacteria, genes encoded on these elements must be properly regulated. Among the legionellae are multiple integrative conjugative elements (ICEs) that each encode a paralog of the broadl...

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Published in:Journal of bacteriology 2016-02, Vol.198 (3), p.553-564
Main Authors: Abbott, Zachary D, Flynn, Kaitlin J, Byrne, Brenda G, Mukherjee, Sampriti, Kearns, Daniel B, Swanson, Michele S
Format: Article
Language:English
Subjects:
Animals
Bacillus subtilis
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacteriology
Binding sites
Bioinformatics
Cell Line
Conjugation, Genetic
Evolutionary biology
Gene expression
Gene Expression Regulation, Bacterial - physiology
Genes, Regulator
Genetics
Gram-negative bacteria
Legionella pneumophila
Legionella pneumophila - genetics
Legionella pneumophila - metabolism
Lysosomes
Macrophages
Mice
Phylogeny
Protein Binding
Protein Transport
RNA, Bacterial - genetics
RNA, Bacterial - metabolism
RNA-protein interactions
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Summary:Bacterial evolution is accelerated by mobile genetic elements. To spread horizontally and to benefit the recipient bacteria, genes encoded on these elements must be properly regulated. Among the legionellae are multiple integrative conjugative elements (ICEs) that each encode a paralog of the broadly conserved regulator csrA. Using bioinformatic analyses, we deduced that specific csrA paralogs are coinherited with particular lineages of the type IV secretion system that mediates horizontal spread of its ICE, suggesting a conserved regulatory interaction. As a first step to investigate the contribution of csrA regulators to this class of mobile genetic elements, we analyzed here the activity of the csrA paralog encoded on Legionella pneumophila ICE-βox. Deletion of this gene, which we name csrT, had no observed effect under laboratory conditions. However, ectopic expression of csrT abrogated the protection to hydrogen peroxide and macrophage degradation that ICE-βox confers to L. pneumophila. When ectopically expressed, csrT also repressed L. pneumophila flagellin production and motility, a function similar to the core genome's canonical csrA. Moreover, csrT restored the repression of motility to csrA mutants of Bacillus subtilis, a finding consistent with the predicted function of CsrT as an mRNA binding protein. Since all known ICEs of legionellae encode coinherited csrA-type IV secretion system pairs, we postulate that CsrA superfamily proteins regulate ICE activity to increase their horizontal spread, thereby expanding L. pneumophila versatility. ICEs are mobile DNA elements whose type IV secretion machineries mediate spread among bacterial populations. All surveyed ICEs within the Legionella genus also carry paralogs of the essential life cycle regulator csrA. It is striking that the csrA loci could be classified into distinct families based on either their sequence or the subtype of the adjacent type IV secretion system locus. To investigate whether ICE-encoded csrA paralogs are bona fide regulators, we analyzed ICE-βox as a model system. When expressed ectopically, its csrA paralog inhibited multiple ICE-βox phenotypes, as well as the motility of not only Legionella but also Bacillus subtilis. Accordingly, we predict that CsrA regulators equip legionellae ICEs to promote their spread via dedicated type IV secretion systems.
ISSN:0021-9193
1098-5530
DOI:10.1128/JB.00732-15