Non-typeable Haemophilus influenzae isolates from patients with chronic obstructive pulmonary disease contain new phase-variable modA methyltransferase alleles controlling phasevarions

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Atack, John M
Murphy, Timothy F
Ettigrew, Melinda MP
Seib, Kate L
Jennings, Michael P
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2019
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Abstract

Phasevarions (phase-variable regulons) are emerging as an important area of bacterial gene regulation. Many bacterial pathogens contain phasevarions, with gene expression controlled by the phase-variable expression of DNA methyltransferases via epigenetic mechanisms. Non-typeable Haemophilus influenzae (NTHi) contains the phase-variable methyltransferase modA, of which multiple allelic variants exist (modA1-21). We have previously demonstrated 5 of 21 these modA alleles are overrepresented in NTHi strains isolated from children with middle ear infections. In this study we investigated the modA allele distribution in NTHi strains isolated from patients with chronic obstructive pulmonary disease, COPD. We demonstrate that the distribution of modA alleles in a large panel of COPD isolates is different to the distribution seen in middle ear infections, suggesting different modA alleles may provide distinct advantages in the differing niches of the middle ear and COPD airways. We also identified two new phase-variable modA alleles – modA15 and modA18 – and demonstrate that these alleles methylate distinct DNA sequences and control unique phasevarions. The modA15 and modA18 alleles have only been observed in COPD isolates, indicating that these two alleles may be markers for isolates likely to cause exacerbations of COPD.

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Scientific Reports

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9

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1

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© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Bacteriology

Genetics

Clinical sciences

Science & Technology

Multidisciplinary Sciences

Science & Technology - Other Topics

DNA RESTRICTION

EPIGENETIC REGULATORS

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Atack, JM; Murphy, TF; Ettigrew, MMP; Seib, KL; Jennings, MP, Non-typeable Haemophilus influenzae isolates from patients with chronic obstructive pulmonary disease contain new phase-variable modA methyltransferase alleles controlling phasevarions, Scientific Reports, 2019, 9 (1)

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