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Artesunate enhances the antibacterial effect of {beta}-lactam antibiotics against Escherichia coli by increasing antibiotic accumulation via inhibition of the multidrug efflux pump system AcrAB-TolC.
J Antimicrob Chemother 2011; 66(4):769-77JA

Abstract

OBJECTIVES

Occasionally, we found that artesunate enhanced the antibacterial effects of antibiotics in vitro. Therefore, the enhancement of various β-lactam antibiotics by artesunate against Escherichia coli and the possible mechanism were investigated in the present study.

METHODS

Antibacterial effects were observed using the serial 2-fold dilution method and dynamic bacterial growth. Daunomycin accumulation within E. coli was observed using fluorospectrophotometry and laser confocal scanning microscopy. AcrAB-TolC, AmpC and TEM-1 mRNA expression was observed using a PCR method. Antisense oligonucleotides (as-ODNs) targeting AcrB were designed and used to block AcrB gene expression within E. coli ATCC 35218.

RESULTS

Although artesunate itself had no antibacterial ability, artesunate significantly increased the antibacterial effect of β-lactam antibiotics against E. coli ATCC 35218 and an E. coli clinical strain. Artesunate increased daunomycin accumulation within E. coli ATCC 35218 in a dose-dependent manner and reduced the mRNA expression of AcrAB-TolC, an important multidrug efflux system for Gram-negative bacteria. The bacterial number was significantly reduced by as-ODN targeting AcrB, but did not further decrease after additional artesunate treatment. In contrast, artesunate lost its enhancement of β-lactam antibiotics against E. coli AG100A, a strain lacking the gene encoding AcrAB, and artesunate did not increase daunomycin accumulation within E. coli AG100A. After the transformation of pET28a-AcrB into E. coli AG100A, artesunate regained enhancement of β-lactam antibiotics. Furthermore, artesunate did not inhibit the expression of AmpC and TEM-1 mRNA.

CONCLUSIONS

Artesunate enhances the antibacterial effect of various β-lactam antibiotics against E. coli, which might be associated with the suppression of a major multidrug resistance system, AcrAB-TolC.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmacy, The Third Military Medical University, and Medical Research Center, Southwestern Hospital, Chongqing 400038, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21393180

Citation

Li, Bin, et al. "Artesunate Enhances the Antibacterial Effect of {beta}-lactam Antibiotics Against Escherichia Coli By Increasing Antibiotic Accumulation Via Inhibition of the Multidrug Efflux Pump System AcrAB-TolC." The Journal of Antimicrobial Chemotherapy, vol. 66, no. 4, 2011, pp. 769-77.
Li B, Yao Q, Pan XC, et al. Artesunate enhances the antibacterial effect of {beta}-lactam antibiotics against Escherichia coli by increasing antibiotic accumulation via inhibition of the multidrug efflux pump system AcrAB-TolC. J Antimicrob Chemother. 2011;66(4):769-77.
Li, B., Yao, Q., Pan, X. C., Wang, N., Zhang, R., Li, J., ... Zhou, H. (2011). Artesunate enhances the antibacterial effect of {beta}-lactam antibiotics against Escherichia coli by increasing antibiotic accumulation via inhibition of the multidrug efflux pump system AcrAB-TolC. The Journal of Antimicrobial Chemotherapy, 66(4), pp. 769-77. doi:10.1093/jac/dkr017.
Li B, et al. Artesunate Enhances the Antibacterial Effect of {beta}-lactam Antibiotics Against Escherichia Coli By Increasing Antibiotic Accumulation Via Inhibition of the Multidrug Efflux Pump System AcrAB-TolC. J Antimicrob Chemother. 2011;66(4):769-77. PubMed PMID: 21393180.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Artesunate enhances the antibacterial effect of {beta}-lactam antibiotics against Escherichia coli by increasing antibiotic accumulation via inhibition of the multidrug efflux pump system AcrAB-TolC. AU - Li,Bin, AU - Yao,Qi, AU - Pan,Xi-Chun, AU - Wang,Ning, AU - Zhang,Rong, AU - Li,Jun, AU - Ding,Guofu, AU - Liu,Xin, AU - Wu,Chong, AU - Ran,Dongzhi, AU - Zheng,Jiang, AU - Zhou,Hong, Y1 - 2011/02/09/ PY - 2011/3/12/entrez PY - 2011/3/12/pubmed PY - 2011/7/16/medline SP - 769 EP - 77 JF - The Journal of antimicrobial chemotherapy JO - J. Antimicrob. Chemother. VL - 66 IS - 4 N2 - OBJECTIVES: Occasionally, we found that artesunate enhanced the antibacterial effects of antibiotics in vitro. Therefore, the enhancement of various β-lactam antibiotics by artesunate against Escherichia coli and the possible mechanism were investigated in the present study. METHODS: Antibacterial effects were observed using the serial 2-fold dilution method and dynamic bacterial growth. Daunomycin accumulation within E. coli was observed using fluorospectrophotometry and laser confocal scanning microscopy. AcrAB-TolC, AmpC and TEM-1 mRNA expression was observed using a PCR method. Antisense oligonucleotides (as-ODNs) targeting AcrB were designed and used to block AcrB gene expression within E. coli ATCC 35218. RESULTS: Although artesunate itself had no antibacterial ability, artesunate significantly increased the antibacterial effect of β-lactam antibiotics against E. coli ATCC 35218 and an E. coli clinical strain. Artesunate increased daunomycin accumulation within E. coli ATCC 35218 in a dose-dependent manner and reduced the mRNA expression of AcrAB-TolC, an important multidrug efflux system for Gram-negative bacteria. The bacterial number was significantly reduced by as-ODN targeting AcrB, but did not further decrease after additional artesunate treatment. In contrast, artesunate lost its enhancement of β-lactam antibiotics against E. coli AG100A, a strain lacking the gene encoding AcrAB, and artesunate did not increase daunomycin accumulation within E. coli AG100A. After the transformation of pET28a-AcrB into E. coli AG100A, artesunate regained enhancement of β-lactam antibiotics. Furthermore, artesunate did not inhibit the expression of AmpC and TEM-1 mRNA. CONCLUSIONS: Artesunate enhances the antibacterial effect of various β-lactam antibiotics against E. coli, which might be associated with the suppression of a major multidrug resistance system, AcrAB-TolC. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/21393180/Artesunate_enhances_the_antibacterial_effect_of_{beta}_lactam_antibiotics_against_Escherichia_coli_by_increasing_antibiotic_accumulation_via_inhibition_of_the_multidrug_efflux_pump_system_AcrAB_TolC_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkr017 DB - PRIME DP - Unbound Medicine ER -