Naringenin Microsphere as a Novel Adjuvant Reverses Colistin Resistance via Various Strategies against Multidrug-Resistant Klebsiella pneumoniae Infection

The efficacy of colistin, the last option against multidrug-resistant (MDR) Gram-negative bacteria, is severely threatened by the prevalence of plasmid-or chromosome-mediated colistin resistance genes. Herein, naringenin has dramatically restored colistin sensitivity against colistin-resistant Klebsiella pneumoniae infection without affecting bacterial viability, inducing resistance and causing obvious cell toxicity. Mechanism analysis reveals that naringenin potentiates colistin activity by multiple strategies including inhibition of mobilized colistin resistance gene activity, repression of two-component system regulation, and acceleration of reactive oxygen species-mediated oxidative damage. A lung-targeted delivery system of naringenin microspheres has been designed to facilitate naringenin bioavailability, accompanied by an effective potentiation of colistin for Klebsiella pneumoniae infection. Consequently, a new recognition of naringenin microspheres has been elucidated to restore colistin efficacy against colistin-resistant Gram-negative pathogens, which may be an effective strategy of developing potential candidates for MDR Gramnegative bacteria infection.

Automated summary

Naringenin enhances the activity of colistin against colistin-resistant Klebsiella pneumoniae by inhibiting colistin resistance gene activity, repressing two-component system regulation, and accelerating oxidative damage mediated by reactive oxygen species. A lung-targeted delivery system of naringenin microspheres is designed to increase bioavailability and effectively potentiate colistin for Klebsiella pneumoniae infection.