The spread of antibiotic resistance: understanding the molecular / energetic burden of plasmid acquisition

Resistance genes, carried by plasmids, disseminate within and between commensal and pathogen populations via conjugation and it has been suggested that reducing the use of antibiotics can reduce the prevalence of antibiotic resistance. However Fischer et al (2014) argue that only reducing the use of antibiotics may not be that effective in preventing spread of resistance as they have shown that resistance plasmid persist in in vitro cultures and in vivo without the use of antibiotics.

Reducing antibiotic use may be a worthy approach provided the antibiotic resistance and plasmids impose a fitness cost on the bacteria in the absence of the antibiotic either by reducing the efficiency of a vital metabolic reaction or imposing additional load on the metabolic machinery of the bacteria. An important issue raised here is the potential metabolic burden that introduction of a plasmid into a bacterium can impose, a little studied topic requiring deeper analysis. Importantly, if the burden is identified this may be exploited to find metabolic ways to select against strains that acquire such plasmids.

The aim of this study is to reduce if not eliminate the spread of these highly mobile plasmids. Several authors have reported a decrease in the growth rate of cells that contain plasmids in comparison to those that are plasmid free most probably due to the burden of plasmid replication, rDNA transcription and plasmid encoded protein translation. To date, the approaches used to determine metabolic burden include 13C flux technology, DNA micro array and enzyme activity analysis but the use of NMR for this purpose has yet to be exploited. Our contention is that plasmid acquisition will exert a metabolic burden upon the host bacterium resulting in metabolite profile changes that will be detected by NMR approaches. Comparative studies of the NMR profiles of bacteria before and after introducing a variety of plasmids.

The long term aim is to understand the burden of resistance in a specific animal production system, poultry, where the burden of antibitic resistance is very high. By understanding metabolic shifts we may identify new targets to aid in control and/or elimination of antibiotic resistance plasmids. Potential candidate are welcome to contact Martin Woodward on [Email Address Removed]