ORCID Profile
0000-0002-3054-8910
Current Organisations
University of Tasmania
,
Saint Louis University School of Medicine
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Publisher: Springer Science and Business Media LLC
Date: 28-07-2015
DOI: 10.1038/NCOMMS8828
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.
Publisher: American Society for Microbiology
Date: 25-06-2019
Abstract: Host-adapted bacterial pathogens such as NTHi cannot survive out of their host environment and have evolved host-specific mechanisms to obtain nutrients and evade the immune response. Relatively few of these host adaptations have been characterized at the molecular level. NTHi utilizes sialic acid as a nutrient and also incorporates this sugar into LOS, which is important in biofilm formation and immune evasion. In the present study, we showed that NTHi has evolved to preferentially utilize the Neu5Ac form of sialic acid. This adaptation is due to the substrate preference of the enzyme CMP-Neu5Ac synthetase, which synthesizes the activated form of Neu5Ac for macromolecule biosynthesis. This adaptation allows NTHi to evade killing by a human antibody response against the nonhuman sialic acid Neu5Gc.
Publisher: Wiley
Date: 27-03-2013
Abstract: To update progress on the effectiveness of vaccine for prevention of acute otitis media (AOM) and identification of promising candidate antigens against Streptococcus pneumoniae , nontypeable Haemophilus influenzae , and Moraxella catarrhalis . Literature searches were performed in OvidSP and PubMed restricted to articles published between June 2007 and September 2011. Search terms included otitis media, vaccines, vaccine antigens , and each of the otitis pathogens and candidate antigens identified in the ninth conference report. The current report provides further evidence for the effectiveness of pneumococcal conjugate vaccines (PCVs) in the prevention of otitis media. Observational studies demonstrate a greater decline in AOM episodes than reported in clinical efficacy trials. Unmet challenges include extending protection to additional serotypes and additional pathogens, the need to prevent early episodes, the development of correlates of protection for protein antigens, and the need to define where an otitis media vaccine strategy fits with priorities for child health. Acute otitis media continues to be a burden on children and families, especially those who suffer from frequent recurrences. The 7‐valent PCV (PCV7) has reduced the burden of disease as well as shifted the pneumococcal serotypes and the distribution of otopathogens currently reported in children with AOM. Antibiotic resistance remains an ongoing challenge. Multiple candidate antigens have demonstrated the necessary requirements of conservation, surface exposure, immunogenicity, and protection in animal models. Further research on the role of each antigen in pathogenesis, in the development of correlates of protection in animal models, and in new adjuvants to elicit responses in the youngest infants is likely to be productive and permit more antigens to move into human clinical trials.
Publisher: Wiley
Date: 27-03-2013
Abstract: The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media. PubMed database of the National Library of Medicine. Three subpanels with co‐chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel. Excellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratory‐based basic studies, cell‐based assays, work in animal models, and clinical studies. The advances of the past 4 years formed the basis of a series of short‐term and long‐term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media.
Publisher: Oxford University Press (OUP)
Date: 23-02-2015
Publisher: Elsevier BV
Date: 09-2018
Location: United States of America
Location: United States of America
Location: United States of America
No related grants have been discovered for Stephen Barenkamp.