國家衛生研究院 NHRI:Item 3990099045/8622
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    題名: Regulation of AcrAB-TolC and the roles of this efflux pump on antibiotic resistance and virulence in Klebsiella pneumoniae
    作者: Tsai, YK;Chang, JC;Liou, CH;Hsiao, YW;Ma, L;Huang, LY;Lin, FM;Ding, YJ;Chen, PJ;Siu, LK
    貢獻者: Division of Infectious Diseases
    摘要: Purpose: The regulation mechanism of the AcrAB-TolC efflux pump in Klebsiella pneumoniae remains unclear. This study clarified this mechanism and further evaluated the roles of this efflux pump on antibiotic resistance and virulence in K. pneumoniae. Methods: In-frame deletion mutagenesis was used to generate the deletions of the acrB, tolC and the potential regulator genes of the AcrAB-TolC (acrR, ramR, marR, soxR and rob) in K. pneumoniae strains HK1269S and NVT2001S, which belong to capsular serotype K1 and K2, respectively. The gene expression levels and antibiotic susceptibility was determined, while the virulence was assessed by in vitro and in vivo studies. Results: In both of the two K. pneumoniae strains, the deletion of acrR, marR, soxR or rob showed slight effects on the expression levels of acrB, tolC and ramA, while the deletion of ramR significantly increased these expressions. Compared to their parental strains, the ΔramR strains showed a significant (≥4-fold) increase in the MICs of multiple antibiotics, and the ΔacrB and ΔtolC strains exhibited a significant (≥4-fold) decrease, while no significant differences were found in the ΔacrR, ΔmarR, ΔsoxR and Δrob strains. Compared with the serum-resistance strain NVT2001S, its ΔramR strain became susceptible to serum, and ∼5.7- and ∼11.7-fold smaller survival rates (P<0.05) in serum were found in its ΔacrB and ΔtolC strains, respectively. The deletion of ramR also caused a ∼8.7-fold smaller survival rate (P<0.05) in serum in the serum-susceptible strain HK1269S. In a mouse peritonitis model, the ΔacrB strains showed no change in virulence, while and ΔramR and ΔtolC strains presented significantly (P<0.05) lower virulence. Conclusions: The AcrAB-TolC efflux pump in K. pneumoniae is mainly regulated by the ramR and ramA genes. The ramR deletion in K. pneumoniae confers the overexpression of AcrAB-TolC and results in the antibiotic-resistance increase and virulence reduction at the same time.
    日期: 2015-04
    關聯: Journal of Microbiology, Immunology and Infection. 2015 Apr;48(2, Suppl.1):S173-S174.
    Link to: http://dx.doi.org/10.1016/j.jmii.2015.02.608
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1684-1182&DestApp=IC2JCR
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