Characterization of Fitness Cost Caused by Tigecycline-Resistance Gene tet(X6) in Different Host Bacteria

Abstract

The emergence and prevalence of the <i>tet</i>(X) gene and its variants in the environment and in clinical settings constitute a growing concern for public health worldwide. Accordingly, the tigecycline resistance gene variant <i>tet</i>(X6) is widely detected in <i>Proteus</i> spp. and <i>Acinetobacter</i> spp. rather than Enterobacteriaceae, while the underpinning behind this phenomenon is still unclear. To investigate the mechanisms underlying this distinct phenomenon, we assessed the fitness of the engineered plasmid pBAD-<i>tet</i>(X6) in different host bacteria by monitoring their growth curves, relative fitness and the ability of biofilm formation, as well as virulence in a <i>Galleria mellonella</i> model. MIC and qRT-PCR analysis indicated the successful expression of the <i>tet</i>(X6) gene in these strains in the presence of l-arabinose. Furthermore, we found that pBAD-<i>tet</i>(X6) displayed the lowest fitness cost in <i>P. mirabilis</i> compared with that in <i>E. coli</i> or <i>S.</i> Enteritidis, suggesting the fitness difference of <i>tet</i>(X6)-bearing plasmids in different host bacteria. Consistently, the carriage of pBAD-<i>tet</i>(X6) remarkably reduced the biofilm production and virulence of <i>E. coli</i> or <i>S.</i> Enteritidis. These findings not only indicate that the fitness cost difference elicited by the <i>tet</i>(X6) gene may be responsible for its selectivity in host bacteria but also sheds new insight into the dissemination of antibiotic resistance genes (ARGs) in clinical and environmental isolates.