The mobile dso-gene-sso element in rolling-circle plasmids of staphylococci reflects the evolutionary history of its resistance gene

Abstract

The qacC and lnuA genes of Staphylococcus species were recently proposed to comprise a mobile element when residing on rolling-circle plasmids. Here we present other examples of resistance genes on staphylococcal rolling-circle plasmids, including fosB producing resistance to fosfomycin, cat resulting in resistance to chloramphenicol and cadB for resistance to the toxic heavy metal cadmium. For three of these genes (qacC, lnuA and fosB), evidence was obtained that the genes have spread between different plasmid backgrounds. The lack of mutations in qacC suggests that the spread occurred relatively recently, while the build up of mutations in lnuA and fosB suggests their mobilization occurred in the more distant past. These observations can be explained by the use of the respective antibiotics over time. However, the cat and cadB genes sequences analysed had not collected any mutations, an observation that is not completely understood but possible explanations are discussed. Significance and Impact of the Study: We have analysed five resistance genes in Staphylococcus aureus that are positioned between the replication elements of rolling-circle plasmids. For three of these genes, evidence was obtained indicative of recent mobilization. The historical use of the antibiotics to which the genes produce resistance could be related to the number of mutations collected in these genes. However, two other resistance genes have not collected any mutations over time, and the reasons for this are discussed. The analyses presented provide insights into the spread and evolution of antibiotic resistance genes.