In investigating the epidemiological trends of
Salmonella enterica
serovar Goldcoast, we have previously identified several closely related strains with different MICs to azithromycin and quinolones. Genome sequencing and comparison of two very similar MDR strains, R18.0877 and R18.1656, has led to the identification of an extra plasmid-borne
ramA
gene,
ramAp
, on the large IncHI2 plasmid carried by R18.0877. The
ramAp
is located in a 953-bp region on the plasmid, which is identical to that of the
Klebsiella quasipneumoniae
chromosomal
ramA
loci. A truncated IS
Ecp1
located at the adjacent upstream of the putative regulatory region of the
ramAp
may likely contribute to its mobilization and expression. Introducing the
ramAp
and the truncated IS
Ecp1
into
E. coli
have resulted in elevated expression of efflux pump genes and elevated MICs to chloramphenicol, azithromycin, nalidixic acid, ciprofloxacin, sulfamethoxazole, trimethoprim, tetracycline, and tigecycline. The
ramAp
is an extra efflux pump activator gene that potentially could be transmitted with the IncHI2 plasmid among bacteria. It is plausible that, with high interspecific conservation, the plasmid-encoded regulator reduces drug susceptibility by activating existing efflux pump systems of the host and thus can be regarded as a new type of auxiliary antimicrobial resistance determinant. Sequences of similar plasmids were found worldwide. Its impact on the emergence of antimicrobial resistance among bacterial pathogens is worrisome.