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A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae.

Atack JM, Srikhanta YN, Fox KL, Jurcisek JA, Brockman KL, Clark TA, Boitano M, Power PM, Jen FE, McEwan AG, Grimmond SM, Smith AL, Barenkamp SJ, Korlach J, Bakaletz LO, Jennings MP - Nat Commun (2015)

Bottom Line: 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).Our results indicate that a biphasic epigenetic switch can control bacterial virulence, immunoevasion and niche adaptation in an animal model system.

View Article: PubMed Central - PubMed

Affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.

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 chinchilla model of otitis media show a clear selection for ON switching of modA2 in the middle ear. Our results indicate that a biphasic epigenetic switch can control bacterial virulence, immunoevasion and niche adaptation in an animal model system.

No MeSH data available.


Related in: MedlinePlus

Biofilm formation using modA2ON and OFF strains.(a) Shows biofilm formation using modA2(22)ON. (b) Shows biofilm formation using modA2(24)OFF after 24 h growth on chambered coverglass and visualized using confocal microscopy following LIVE/DEAD BacLight staining. Scale bar shown represents 50 μm.
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f6: Biofilm formation using modA2ON and OFF strains.(a) Shows biofilm formation using modA2(22)ON. (b) Shows biofilm formation using modA2(24)OFF after 24 h growth on chambered coverglass and visualized using confocal microscopy following LIVE/DEAD BacLight staining. Scale bar shown represents 50 μm.

Mentions: Given the selection for modA2ON in the chinchilla middle ear and the importance of biofilm formation in chronicity and recurrence of OM, we assayed these ON and OFF variants for relative ability to form a biofilm in vitro. Chamberslides were inoculated with either NTHI strain 723 modA2(22)ON or modA2(24)OFF and allowed to form biofilms for 24 h before being stained with a viable bacterial stain and subjected to confocal imaging. As shown in Fig. 6, biofilms formed by the modA2ON variant were notably more robust than those formed by modA2OFF.


A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae.

Atack JM, Srikhanta YN, Fox KL, Jurcisek JA, Brockman KL, Clark TA, Boitano M, Power PM, Jen FE, McEwan AG, Grimmond SM, Smith AL, Barenkamp SJ, Korlach J, Bakaletz LO, Jennings MP - Nat Commun (2015)

Biofilm formation using modA2ON and OFF strains.(a) Shows biofilm formation using modA2(22)ON. (b) Shows biofilm formation using modA2(24)OFF after 24 h growth on chambered coverglass and visualized using confocal microscopy following LIVE/DEAD BacLight staining. Scale bar shown represents 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525171&req=5

f6: Biofilm formation using modA2ON and OFF strains.(a) Shows biofilm formation using modA2(22)ON. (b) Shows biofilm formation using modA2(24)OFF after 24 h growth on chambered coverglass and visualized using confocal microscopy following LIVE/DEAD BacLight staining. Scale bar shown represents 50 μm.
Mentions: Given the selection for modA2ON in the chinchilla middle ear and the importance of biofilm formation in chronicity and recurrence of OM, we assayed these ON and OFF variants for relative ability to form a biofilm in vitro. Chamberslides were inoculated with either NTHI strain 723 modA2(22)ON or modA2(24)OFF and allowed to form biofilms for 24 h before being stained with a viable bacterial stain and subjected to confocal imaging. As shown in Fig. 6, biofilms formed by the modA2ON variant were notably more robust than those formed by modA2OFF.

Bottom Line: 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).Our results indicate that a biphasic epigenetic switch can control bacterial virulence, immunoevasion and niche adaptation in an animal model system.

View Article: PubMed Central - PubMed

Affiliation: Institute for Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.

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 chinchilla model of otitis media show a clear selection for ON switching of modA2 in the middle ear. Our results indicate that a biphasic epigenetic switch can control bacterial virulence, immunoevasion and niche adaptation in an animal model system.

No MeSH data available.


Related in: MedlinePlus