Study on collateral sensitivity of tigecycline to colistin-resistant complex.

UNLABELLED

The past decade has witnessed the emergence and spread of carbapenem-resistant complex (CRECC), presenting a significant clinical challenge and urgently demanding new treatment strategies against antimicrobial resistance (AMR). This study focused on the impact of tigecycline on the susceptibility of CRECC isolates to colistin and the collateral sensitivity in CRECC. Under tigecycline pressure, the resistance of five clinically isolated CRECC strains to colistin was converted from resistance to sensitivity. These mutants exhibited significantly higher expression of , and genes, with mutations in the gene. Overexpression of in certain mutants did not alter expression. No mutations were identified in lipid A synthesis genes; however, was consistently downregulated, and expression varied among CRECC405-resistant mutants. Low-dose colistin and tigecycline combination therapy outperformed monotherapy in antimicrobial efficacy. Overall, collateral susceptibility to tigecycline was observed in CRECC isolates with colistin resistance. The overexpression of and , due to mutations, led to tigecycline resistance. Inconsistent expression levels of lipid A synthesis genes affected lipid A modification, which in turn upregulated expression in CRECC405-resistant mutants. Increased sensitivity to colistin was associated with the downregulation of and expression.

IMPORTANCE

Antimicrobial resistance (AMR) is escalating faster than our ability to manage bacterial infections, with antibiotic-resistant bacteria emerging as a significant public health risk. Innovative strategies are urgently needed to curb AMR dissemination. Our research identified collateral sensitivity in complex following tigecycline (TGC) resistance, resulting in newfound sensitivity to colistin (COL), a drug to which it was once resistant. Synergistic tigecycline and colistin therapy significantly suppress bacterial growth, offering a promising approach to combat infections and curb AMR progression through the strategic pairing of antibiotics with complementary sensitivities.