Antimicrobial strategies & resistance

Research Focus

This group is investigating the mechanisms of bacterial resistance to antimicrobials and novel methods of circumventing these.

antimicrobial

The group have established that the oral cavity harbours very high proportions of bacteria resistant to a range of antimicrobials. Of concern was their finding that these high levels of antimicrobial -resistant organisms are present in individuals (including children) who had not recently (within 3 months) been received antimicrobials. Furthermore, resistant species could persist in the mouth for long periods of time (more than 18 months) in the absence of antimicrobial administration. As well as identifying the genes responsible for antimicrobial resistance in oral bacteria, they have identified and characterised novel antimicrobial-resistance genes. Furthermore, the group have demonstrated that genes encoding antimicrobial resistance can transfer between organisms (even those that are distantly-related) both in vitro and in vivo. The group has also carried out extensive investigations into the link in oral bacteria between antimicrobial resistance and resistance to mercury. As well as demonstrating that healthy individuals harbour high levels of oral bacteria that are resistant to both mercury and antimicrobials, they have characterised the genes encoding mercury resistance and have demonstrated that dental amalgam restorations may drive colonisation with bacteria (e.g. Streptococcus oralis) that may be of systemic relevance in the immunocompromised host. The group was the first to delineate the profile of antimicrobial resistance in the endodontic microbiota and to determine that resistance genes can be transferred between bacterial isolates from root canals.

antimicrobial-2

The group has also made significant progress in the development of novel antimicrobial techniques. One particular focus has been on photodynamic therapy, funded by major research councils (BBSRC, EPSRC, MRC), the Charles Wilson Charitable Trust and industry (Ondine Pharma and Dentofex). The group has developed novel photosensitisers which can selectively target killing to specific microorganisms, including meticillin-resistant Staphylococcus aureus (MRSA) and the important periodontopathogen Porphyromonas gingivalis. Translational application has been taken forward with industry (Ondine Biopharma) to produce a treatment system which is now being used clinically, was launched at the Pacific Dental Conference in Vancouver, Canada in 2006 and is currently used by 15% of Canadian dentists. Ondine Biopharma have recently received a CE mark which will enable them to market Periowave in Europe. The sustainable quality of this theme is reflected by securement of funding from EPSRC and Ondine Pharma, extending the application by the development of light-activated antimicrobial coatings, novel photosensitisers and methods to selectively target bacteria.

Another major theme being explored is the use of naturally products with antibacterial, anti-adhesive or anti-inflammatory compounds in the prevention and/or treatment of caries and periodontitis. An international consortium lead by the UCL-EDI group has recently been awarded a major EU grant (2.2 million Euros) to identify, characterise and evaluate compounds present in foods and beverages that may prove useful for the prevention and/or treatment of oral diseases. They plan to incorporate such compounds into oral hygiene products and to develop functional foods containing them.

Research Outcomes

  • Diaz-Torres ML, Villedieu A, Hunt N, McNab R, Spratt DA, Allan E, Mullany P and Wilson M. 2006.
    Determining the antibiotic resistance potential of the indigenous oral microbiota of humans using a metagenomic approach.     FEMS Microbiology Letters 258(2): 257-262
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