Study on the mechanism of rifampicin in reducing the virulence of hvKP and its antimicrobial activity in combination with CRO in vitro and in vivo
Objective To explore the ability of rifampicin(RFP)to reduce the capsule synthesis of hypervirulent Klebsiella pneumoniae(hvKP)and the antibacterial effect of RFP combined with ceftriaxone(CRO)in vitro and in vivo.Methods Four clinical strains that conformed to the criteria for hvKP were screened from Klebsiella pneumoniae isolated from the Affiliated Hospital of Chengde Medical University in 2021.The capsular serotypes of the strains were determined by PCR,and the genotypes of the strains were determined by multilocus sequence typing.Capsular polysaccharide quantification,India ink staining,and fluorescence quantitative PCR were used to analyze the changes in capsule content,capsule diameters,and expression of capsule-related genes of hvKP strains before and after RFP treatment.On this basis,the antibacterial effect of RFP combined with CRO in vitro was detected,and a Galleria mellonella infection model was established to analyze the antibacterial effect of the combination of RFP and CRO in vivo.Results Among the four hvKP strains screened,strains 10 and 35 were K1-ST23 type,strain 12 was K57-ST592 type,and strain 96 was K5-ST485 type.RFP at 1/4 MIC concentration significantly decreased capsular polysaccharide content(P＜0.05),decreased capsule diameters(P＜0.001)and down-regulated the transcription levels of genes involved in capsule synthesis(P＜0.001)without significantly affecting bacterial growth.The FIC index of RFP and CRO combined drug sensitivity test results of 4 strains showed synergistic or partial synergy effects,and the survival rate of Galleria mellonella larvae after hvKP infection treated with CRO+1/4MIC RFP was significantly higher than that of CRO monotherapy(P＜0.05).Conclusion Rifampicin has the anti-virulence ability to inhibit hvKP capsule synthesis and can improve the efficacy of antibacterial drugs by reducing mucus production and enhancing drug permeability.
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