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ModM DNA methyltransferase methylome analysis reveals a potential role for Moraxella catarrhalis phasevarions in otitis media
Author(s) -
Blakeway Luke V.,
Power Peter M.,
Jen Freda E.C.,
Worboys Sam R.,
Boitano Matthew,
Clark Tyson A.,
Korlach Jonas,
Bakaletz Lauren O.,
Jennings Michael P.,
Peak Ian R.,
Seib Kate L.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-256578
Subject(s) - moraxella catarrhalis , dna methylation , biology , dna methyltransferase , allele , otitis , gene , methylation , genetics , methyltransferase , gene expression , streptococcus pneumoniae , bacteria
Moraxella catarrhalis is a significant cause of otitis media and exacerbations of chronic obstructive pulmonary disease. Here, we characterize a phase‐variable DNA methyltransferase (ModM), which contains 5′‐CAAC‐3′ repeats in its open reading frame that mediate high‐frequency mutation resulting in reversible on/off switching of ModM expression. Three modM alleles have been identified ( modM1–3 ), with modM2 being the most commonly found allele. Using single‐molecule, real‐time (SMRT) genome sequencing and methylome analysis, we have determined that the ModM2 methylation target is 5′‐GAR m6 AC‐3′, and 100% of these sites are methylated in the genome of the M. catarrhalis 25239 ModM2 on strain. Proteomic analysis of ModM2 on and off variants revealed that ModM2 regulates expression of multiple genes that have potential roles in colonization, infection, and protection against host defenses. Investigation of the distribution of modM alleles in a panel of M. catarrhalis strains, isolated from the nasopharynx of healthy children or middle ear effusions from patients with otitis media, revealed a statistically significant association of modM3 with otitis media isolates. The modulation of gene expression via the ModM phase‐variable regulon (phasevarion), and the significant association of the modM3 allele with otitis media, suggests a key role for ModM phasevarions in the pathogenesis of this organism.—Blakeway, L. V., Power, P. M., Jen, F., E.‐C., Worboys, S. R., Boitano, M., Clark, T. A., Korlach, J., Bakaletz, L. O., Jennings, M. P., Peak, I. R., Seib, K. L., ModM DNA methyltransferase methylome analysis reveals a potential role for Moraxella catarrhalis phasevarions in otitis media. FASEB J. 28, 5197–5207 (2014). www.fasebj.org