Medicine (Austin & Northern Health) - Research Publications

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    Correlation between Buruli Ulcer and Vector-borne Notifiable Diseases, Victoria, Australia
    Johnson, PDR ; Lavender, CJ (CENTERS DISEASE CONTROL, 2009-04)
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    Mycobacterium ulcerans in mosquitoes captured during outbreak of buruli ulcer, Southeastern Australia
    Johnson, PDR ; Azuolas, J ; Lavender, CJ ; Wishart, E ; Stinear, TP ; Hayman, JA ; Brown, L ; Jenkin, GA ; Fyfe, JAM (CENTER DISEASE CONTROL, 2007-11)
    Buruli ulcer (BU) occurs in >30 countries. The causative organism, Mycobacterium ulcerans, is acquired from the environment, but the exact mode of transmission is unknown. We investigated an outbreak of BU in a small coastal town in southeastern Australia and screened by PCR mosquitoes caught there. All cases of BU were confirmed by culture or PCR. Mosquitoes were trapped in multiple locations during a 26-month period. BU developed in 48 residents of Point Lonsdale/Queenscliff and 31 visitors from January 2001 through April 2007. We tested 11,504 mosquitoes trapped at Point Lonsdale (predominantly Aedes camptorhynchus). Forty-eight pools (5 species) were positive for insertion sequence IS2404 (maximum likelihood estimate 4.3/1,000), and we confirmed the presence of M. ulcerans in a subset of pools by detection of 3 additional PCR targets.
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    Risk Factors forMycobacterium ulceransInfection, Southeastern Australia
    Quek, TYJ ; Athan, E ; Henry, MJ ; Pasco, JA ; Redden-Hoare, J ; Hughes, A ; Johnson, PDR (Centers for Disease Control and Prevention (CDC), 2007-11)
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    Different bacterial gene expression patterns and attenuated host immune responses are associated with the evolution of low-level vancomycin resistance during persistent methicillin-resistant Staphylococcus aureus bacteraemia
    Howden, BP ; Smith, DJ ; Mansell, A ; Johnson, PDR ; Ward, PB ; Stinear, TP ; Davies, JK (BIOMED CENTRAL LTD, 2008-02-27)
    BACKGROUND: Low-level vancomycin resistance in Staphylococcus aureus (vancomycin-intermediate S. aureus (VISA) and hetero-VISA [hVISA]) emerges during persistent infection and failed vancomycin therapy. Up-regulation of genes associated with the "cell wall stimulon" and mutations in the vraSR operon have both been implicated in the development of resistance, however the molecular mechanisms of resistance are not completely understood. To further elucidate the mechanisms leading to resistance transcriptome comparisons were performed using multiple clinical pairs of vancomycin-susceptible S. aureus (VSSA) and hVISA/VISA (n = 5), and three VSSA control pairs from hospitalized patients with persistent bacteraemia that did not develop hVISA/VISA. Based on the transcriptome results multiple genes were sequenced and innate immune system stimulation was assessed in the VSSA and hVISA/VISA pairs. RESULTS: Here we show that up-regulation of vraS and the "cell wall stimulon" is not essential for acquisition of low-level vancomycin resistance and that different transcriptional responses occur, even between closely related hVISA/VISA strains. DNA sequencing of vraSR, saeSR, mgrA, rot, and merR regulatory genes and upstream regions did not reveal any differences between VSSA and hVISA/VISA despite transcriptional changes suggesting mutations in these loci may be linked to resistance in these strains. Enhanced capsule production and reduced protein A expression in hVISA/VISA were confirmed by independent bioassays and fully supported the transcriptome data. None of these changes were observed in the three control pairs that remained vancomycin-susceptible during persistent bacteremia. In a macrophage model of infection the changes in cell surface structures in hVISA/VISA strains were associated with significantly reduced NF-kappaB activation resulting in reduced TNF-alpha and IL-1beta expression. CONCLUSION: We conclude that there are multiple pathways to low-level vancomycin resistance in S. aureus, even among closely related clinical strains, and these can result in an attenuated host immune response. The persistent infections associated with hVISA/VISA strains may be a consequence of changes in host pathogen interactions in addition to the reduced antibiotic susceptibility.
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    Buruli ulcer (M-ulcerans infection):: New insights, new hope for disease control (vol 2, pg 282, 2005)
    Johnson, PDR ; Stinear, T ; Small, PLC ; Pluschke, G ; Merritt, RW ; Portaels, F ; Huygen, K ; Hayman, JA ; Asiedu, K (PUBLIC LIBRARY SCIENCE, 2005-05)
    Buruli ulcer is a disease of skin and soft tissue caused by Mycobacterium ulcerans. It can leave affected people scarred and disabled. What are the prospects for disease control?
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    Successful treatment of Mycobacterium ulcerans osteomyelitis with minor surgical debridement and prolonged rifampicin and ciprofloxacin therapy: a case report.
    O'Brien, DP ; Athan, E ; Hughes, A ; Johnson, PD (Springer Science and Business Media LLC, 2008-04-27)
    INTRODUCTION: Treatment for osteomyelitis-complicating Mycobacterium ulcerans infection typically requires extensive surgery and even amputation, with no reported benefit from adjunctive antibiotics. CASE PRESENTATION: We report a case of an 87-year-old woman with M. ulcerans osteomyelitis that resolved following limited surgical debridement and 6 months of therapy with rifampicin and ciprofloxacin. CONCLUSION: M. ulcerans osteomyelitis can be successfully treated with limited surgical debridement and adjunctive oral antibiotics.
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    First Isolation of Mycobacterium ulcerans from an Aquatic Environment: The End of a 60-Year Search?
    Stinear, T ; Johnson, PDR ; Picardeau, M (PUBLIC LIBRARY SCIENCE, 2008-03)
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    Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer
    Stinear, TP ; Seemann, T ; Pidot, S ; Frigui, W ; Reysset, G ; Garnier, T ; Meurice, G ; Simon, D ; Bouchier, C ; Ma, L ; Tichit, M ; Porter, JL ; Ryan, J ; Johnson, PDR ; Davies, JK ; Jenkin, GA ; Small, PLC ; Jones, LM ; Tekaia, F ; Laval, F ; Daffe, M ; Parkhill, J ; Cole, ST (COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2007-02)
    Mycobacterium ulcerans is found in aquatic ecosystems and causes Buruli ulcer in humans, a neglected but devastating necrotic disease of subcutaneous tissue that is rampant throughout West and Central Africa. Here, we report the complete 5.8-Mb genome sequence of M. ulcerans and show that it comprises two circular replicons, a chromosome of 5632 kb and a virulence plasmid of 174 kb. The plasmid is required for production of the polyketide toxin mycolactone, which provokes necrosis. Comparisons with the recently completed 6.6-Mb genome of Mycobacterium marinum revealed >98% nucleotide sequence identity and genome-wide synteny. However, as well as the plasmid, M. ulcerans has accumulated 213 copies of the insertion sequence IS2404, 91 copies of IS2606, 771 pseudogenes, two bacteriophages, and multiple DNA deletions and rearrangements. These data indicate that M. ulcerans has recently evolved via lateral gene transfer and reductive evolution from the generalist, more rapid-growing environmental species M. marinum to become a niche-adapted specialist. Predictions based on genome inspection for the production of modified mycobacterial virulence factors, such as the highly abundant phthiodiolone lipids, were confirmed by structural analyses. Similarly, 11 protein-coding sequences identified as M. ulcerans-specific by comparative genomics were verified as such by PCR screening a diverse collection of 33 strains of M. ulcerans and M. marinum. This work offers significant insight into the biology and evolution of mycobacterial pathogens and is an important component of international efforts to counter Buruli ulcer.