The role of natural antimicrobials in selection for antibiotic resistance
Main supervisor: Dr Michiel Vos
Co-supervisor(s): Prof Will Gaze (University of Exeter),Prof Ed Feil (University of Bath), Dr Ruth Airs (Plymouth Marine Laboratory), (), ()
Contact number: 7553491614
Host institution: University of Exeter
The increasing prevalence of antimicrobial resistance (AMR) in bacteria is one of the most pressing problems in global health care. Selection for antibiotic resistance occurs through antibiotic use in the clinic and community and contamination of the environment with heavy metals, biocides and antibiotic residues. However, AMR mechanisms are ancient and their presence in environments with no or minimal exposure to human activity indicates that not all AMR selection is anthropogenic. It is here proposed to test for the first time whether naturally produced antimicrobials can select for resistance to clinical antibiotics. Virtually all organisms, from bacteria to humans, produce antimicrobial compounds. Selection for resistance to these antimicrobials has the potential to also result in resistance to clinical antibiotics when the same bacterial pathways are targeted. Although the ubiquity of interactions between bacteria and antimicrobial producers offers great potential for the molecular diversification of AMR mechanisms, the extent of cross-resistance between naturally produced antimicrobials and clinical antibiotics has remained virtually unstudied.
Seaweeds form a diverse and abundant component of coastal ecosystems and commonly exhibit antimicrobial activity. Seaweed species are colonized by distinct bacterial assemblages, and this process is at least in part mediated by a high diversity of exuded secondary metabolites. Recent research in my lab (Colclough etal in prep) has demonstrated that Staphylococcus aureus strains that were more resistant to clinical antibiotics were on average also more resistant to seaweed extracts. The fact that seaweeds can select for bacteria that are resistant to their metabolites and the observation of cross-resistance between seaweed antimicrobials and clinical antibiotics suggests that there is potential for seaweeds to select for AMR. This PhD project will 1) test whether distinct seaweeds harbour distinct antibiotic resistance genes using metagenomic sequencing, 2) test whether reservoirs of resistance genes can be transferred from seaweed-associated bacterial metagenomes to opportunistic pathogens using functional metagenomics and 3) identify human pathogens on seaweeds and test whether they are more resistant to antibiotics than conspecifics from other environmental reservoirs using whole genome sequencing.
It is critical to understand natural processes governing selection for AMR in the environment. It has been estimated that there are over six million exposure events to cephalosporin-resistant E. coli through recreational use of coastal bathing water in England and Wales alone, demonstrating the potential risks of environmental reservoirs of AMR to human health. This project will allow a first insight into the potential of species interactions to select for AMR mechanisms that confer cross-resistance to clinically relevant antibiotics.
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Leonard AF, Zhang L, Balfour AJ, Garside R, Gaze WH. Human recreational exposure to antibiotic resistant bacteria in coastal bathing waters. Environment international. 2015.
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