Journal article
A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae
JM Atack, YN Srikhanta, KL Fox, JA Jurcisek, KL Brockman, TA Clark, M Boitano, PM Power, FEC Jen, AG McEwan, SM Grimmond, AL Smith, SJ Barenkamp, J Korlach, LO Bakaletz, MP Jennings
Nature Communications | Published : 2015
DOI: 10.1038/ncomms8828
Open access
Abstract
Non-typeable Haemophilus influenzae contains an N 6 -adenine DNA-methyltransferase (ModA) that is subject to phase-variable expression (random ON/OFF switching). Five modA alleles, modA2, modA4, modA5, modA9 and modA10, account for over two-thirds of clinical otitis media isolates surveyed. Here, we use single molecule, real-time (SMRT) methylome analysis to identify the DNA-recognition motifs for all five of these modA alleles. Phase variation of these alleles regulates multiple proteins including vaccine candidates, and key virulence phenotypes such as antibiotic resistance (modA2, modA5, modA10), biofilm formation (modA2) and immunoevasion (modA4). Analyses of a modA2 strain in the chinch..
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Awarded by National Institutes of Health
Funding Acknowledgements
Work was supported by NHMRC (Australia) Project Grant 1034401 to M.P.J. and L.O.B., NHMRC Program Grant 565526 to A.G.M. and M.P.J., NHMRC Program Grant to M.P.J. 1071659, Grant NIH/NIDCD (USA) R01DC003915 to L.O.B., and grant NIH/NIAID (USA) R01AI 81887 to S.J.B. iTRAQ analysis was undertaken at APAF, the infrastructure provided by the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS).