Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions
- Author(s)
- Nahar, N; Tram, G; Jen, FE; Phillips, ZN; Weinert, LA; Bossé, JT; Jabbari, JS; Gouil, Q; Du, MRM; Ritchie, ME; Bowden, R; Langford, PR; Tucker, AW; Jennings, MP; Turni, C; Blackall, PJ; Atack, JM;
- Journal Title
- Nucleic Acids Research
- Publication Type
- epub ahead of print
- Abstract
- Actinobacillus pleuropneumoniae is the cause of porcine pleuropneumonia, a severe respiratory tract infection that is responsible for major economic losses to the swine industry. Many host-adapted bacterial pathogens encode systems known as phasevarions (phase-variable regulons). Phasevarions result from variable expression of cytoplasmic DNA methyltransferases. Variable expression results in genome-wide methylation differences within a bacterial population, leading to altered expression of multiple genes via epigenetic mechanisms. Our examination of a diverse population of A. pleuropneumoniae strains determined that Type I and Type III DNA methyltransferases with the hallmarks of phase variation were present in this species. We demonstrate that phase variation is occurring in these methyltransferases, and show associations between particular Type III methyltransferase alleles and serovar. Using Pacific BioSciences Single-Molecule, Real-Time (SMRT) sequencing and Oxford Nanopore sequencing, we demonstrate the presence of the first ever characterised phase-variable, cytosine-specific Type III DNA methyltransferase. Phase variation of distinct Type III DNA methyltransferase in A. pleuropneumoniae results in the regulation of distinct phasevarions, and in multiple phenotypic differences relevant to pathobiology. Our characterisation of these newly described phasevarions in A. pleuropneumoniae will aid in the selection of stably expressed antigens, and direct and inform development of a rationally designed subunit vaccine against this major veterinary pathogen.
- Publisher
- Oxford Academic
- Research Division(s)
- Epigenetics And Development; Advanced Technology And Biology
- PubMed ID
- 36840716
- Publisher's Version
- https://doi.org/10.1093/nar/gkad091
- Open Access at Publisher's Site
https://doi.org/ 10.1093/nar/gkad091- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-03-08 03:16:00
Last Modified: 2023-03-08 04:00:17