AUTHOR=Wassenaar Trudy M. , Ussery David W. , Ingmer Hanne 

TITLE=The qacC Gene Has Recently Spread between Rolling Circle Plasmids of Staphylococcus, Indicative of a Novel Gene Transfer Mechanism

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.01528

DOI=10.3389/fmicb.2016.01528

ISSN=1664-302X

ABSTRACT=<p>Resistance of <italic>Staphylococcus</italic> species to quaternary ammonium compounds, frequently used as disinfectants and biocides, can be attributed to <italic>qac</italic> genes. Most <italic>qac</italic> gene products belong to the Small Multidrug Resistant (SMR) protein family, and are often encoded by rolling-circle (RC) replicating plasmids. Four classes of SMR-type <italic>qac</italic> gene families have been described in <italic>Staphylococcus</italic> species: <italic>qacC, qacG, qacJ</italic>, and <italic>qacH</italic>. Within their class, these genes are highly conserved, but <italic>qacC</italic> genes are extremely conserved, although they are found in variable plasmid backgrounds. The lower degree of sequence identity of these plasmids compared to the strict nucleotide conservation of their <italic>qacC</italic> means that this gene has recently spread. In the absence of insertion sequences or other genetic elements explaining the mobility, we sought for an explanation of mobilization by sequence comparison. Publically available sequences of <italic>qac</italic> genes, their flanking genes and the replication gene that is invariably present in RC-plasmids were compared to reconstruct the evolutionary history of these plasmids and to explain the recent spread of <italic>qacC</italic>. Here we propose a new model that explains how <italic>qacC</italic> is mobilized and transferred to acceptor RC-plasmids without assistance of other genes, by means of its location in between the Double Strand replication Origin (DSO) and the Single-Strand replication Origin (SSO). The proposed mobilization model of this DSO-<italic>qacC</italic>-SSO element represents a novel mechanism of gene mobilization in RC-plasmids, which has also been employed by other genes, such as <italic>lnuA</italic> (conferring lincomycin resistance). The proposed gene mobility has aided to the wide spread of clinically relevant resistance genes in <italic>Staphylococcus</italic> populations.</p>