In a September 2006 Antimicrobial Agents and Chemotherapy article, Dr. Stuart Levy of the Tufts University School of Medicine identified a gene in Yersinia pestis, the causative agent of plague, that was similar to an Escherichia coli gene known to cause multiple antibiotic resistance. The E. coli mar (multiple antibiotic resistance) locus confers resistance to a variety of drugs, oxidative stress agents, and organic solvents. Encoded in the mar locus are transcriptional regulators of a multidrug efflux pump. The MarR protein represses transcription of the efflux pump, whereas the MarA protein increases its expression, thereby activating antibiotic resistance.
Dr. Levy’s lab wanted to determine if the system also existed in Y. pestis, so they scanned the genome to look for similar genes. They were unable to identify an entire mar locus in Y. pestis, but individual genes with homology to marA, marR and the efflux pump were detected. In total, six possible marA genes were identified and two were tested. The first gene, YPO1737, had 36% sequence identity to the E. coli marA and was about the same length, and the other, called marA47YP, encoded a protein more than twice the size of the E. coli MarA but had 47% sequence identity. Both of the genes were overexpressed in E. coli and a non-virulent strain of Y. pestis.