Abstract
The emergence and prevalence of the tet(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 tet(X6) is widely detected in Proteus spp. and Acinetobacter 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-tet(X6) in different host bacteria by monitoring their growth curves, relative fitness and the ability of biofilm formation, as well as virulence in a Galleria mellonella model. MIC and qRT-PCR analysis indicated the successful expression of the tet(X6) gene in these strains in the presence of l-arabinose. Furthermore, we found that pBAD-tet(X6) displayed the lowest fitness cost in P. mirabilis compared with that in E. coli or S. Enteritidis, suggesting the fitness difference of tet(X6)-bearing plasmids in different host bacteria. Consistently, the carriage of pBAD-tet(X6) remarkably reduced the biofilm production and virulence of E. coli or S. Enteritidis. These findings not only indicate that the fitness cost difference elicited by the tet(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.
Highlights
Antimicrobial resistance is a growing global threat to public health and human safety [1]
Tigecycline is a broad-spectrum glycosyl cyclopeptide antibiotic, belonging to the third generation of tetracycline antibiotics [2,3]. It is recognized as the last line of defense for the treatment of multidrug-resistant (MDR) bacterial infections, for carbapenem-resistant Enterobacteriaceae (CRE)
We evaluated the fitness of the engineered plasmid pBAD-tet(X6) in different host bacteria by monitoring their growth curve, relative fitness, the ability of biofilm formation and virulence in a Galleria mellonella model
Summary
Antimicrobial resistance is a growing global threat to public health and human safety [1]. Tigecycline is a broad-spectrum glycosyl cyclopeptide antibiotic, belonging to the third generation of tetracycline antibiotics [2,3]. It is recognized as the last line of defense for the treatment of multidrug-resistant (MDR) bacterial infections, for carbapenem-resistant Enterobacteriaceae (CRE). With the emergence of plasmidmediated high-level tigecycline resistance genes tet(X3/X4), the risk of treatment failure for MDR bacteria is increasing dramatically [4,5]. The tet(X) gene can be transferred horizontally by conjugative plasmids between intra- and inter-species. A novel tet(X) variant named tet(X6) was frequently detected from Proteus spp. The mechanisms by which these tet(X6) plasmids have better adaptability in Proteus spp. remain unclear
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