Transcriptomic Analysis of the Impact of the tet(X4) Gene on the Growth Characteristics and Antibiotic Resistance Phenotypes of Escherichia coli Isolated from Musk Deer

<i>Escherichia coli</i> (<i>E. coli</i>) is a ubiquitous opportunistic pathogen in nature and serves as an important reservoir for antibiotic resistance genes. The <i>tet</i>(X4) gene is a key determinant mediating tigecycline resistance. Although its core resistance mechanism, encoding a flavin-dependent monooxygenase, has been elucidated, the broader impact of the <i>tet</i>(X4) gene on the secondary regulatory networks of <i>E. coli</i> remains not fully understood. In recent years, multiple studies have indicated that the <i>tet</i>(X4) gene participates in pathways contributing to resistance to other antibiotics by regulating the expression of various genes. In this study, <i>E. coli tet</i>(X4) gene deletion and complementation strains were constructed to investigate the mechanisms by which the <i>tet</i>(X4) gene influences the growth characteristics and antibiotic resistance of <i>E. coli</i>. The minimum inhibitory concentrations (MICs) of 24 different antibiotics, as well as the degradation capacities of tetracycline and tigecycline, were determined for the wild-type, deletion, and complementation strains. In addition, a four-week starvation stress experiment was performed under both the presence and absence of sub-inhibitory concentrations of tigecycline, during which the bacterial growth curves, survival rates, and MIC variations were analyzed. Transcriptomic sequencing of the wild-type, deletion, and complementation strains identified 531 differentially expressed genes associated with ABC transporter activity, drug metabolism, and bacterial two-component systems. These findings provide reliable evidence for elucidating the mechanism by which the <i>tet</i>(X4) gene affects <i>E. coli</i> resistance, offering valuable insights into the prevention and control of tigecycline-resistant <i>E. coli</i> infections.