title: Synergistic effects of baicalein with cefotaxime against Klebsiella pneumoniae through inhibiting CTX-M-1 gene expression.
abstract: Generation of extended- spectrum β- lactamases is one of the major mechanisms by which clinical Klebsiella pneumoniae develop resistance to antibiotics. Combined antibiotics prove to be a relatively effective method of controlling such resistant strains. Some of Chinese herbal active ingredients are known to have synergistic antibacterial effects. This study is aimed to investigate synergistic effects of Chinese herbal active ingredients with cefotaxime on the extended- spectrum β- lactamase positive strains of Klebsiella pneumoniae, and to analyze mechanism of synergistic action, providing experimental evidence for clinical application of antimicrobial drugs.
  
  
  
  For total sixteen strains including fifteen strains of cefotaxime resistant K. pneumoniae and one extended- spectrum β- lactamase positive standard strain, the synergy rates of cefotaxime with baicalein, matrine, and clavulanic acid were 56.3 %, 0 %, and 100 %, respectively. The fractional inhibitory concentration index of combined baicalein and cefotaxime was correlated with the percentage decrease of cefotaxime MIC of all the strains (r = -0.78, p <0.01). In the group of synergy baicalein and cefotaxime, the transcribed mRNA level of CTX-M-1 after treatment of baicalein was decreased significantly (p <0.05). Moreover, the CTX-M-1 mRNA expression percentage inhibition (100 %, 5/5) was significantly higher than non- synergy group (25 %, 1/4) (p <0.05).
  
  
  
  Our study demonstrated that baicalein exhibited synergistic activity when combined with cefotaxime against some of extended- spectrum β- lactamases positive K. pneumoniae strains by inhibiting CTX-M-1 mRNA expression. However, no direct bactericidal or bacteriostatic activity was involved in the synergistic action. Baicalein seems to be a promising novel effective synergistic antimicrobial agent.
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.|Department of Microbiology and Immunology, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China.
authors: Wenhui
authors: W
authors: Cai
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.|Heilongjiang Provincial Key Laboratory of Infection and Immunity, Harbin Medical University, Harbin, China.
authors: Yingmei
authors: Y
authors: Fu
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.
authors: Wenli
authors: W
authors: Zhang
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.|Heilongjiang Provincial Key Laboratory of Infection and Immunity, Harbin Medical University, Harbin, China.
authors: Xiaobei
authors: X
authors: Chen
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.|Heilongjiang Provincial Key Laboratory of Infection and Immunity, Harbin Medical University, Harbin, China.
authors: Jizi
authors: J
authors: Zhao
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.|Heilongjiang Provincial Key Laboratory of Infection and Immunity, Harbin Medical University, Harbin, China.
authors: Wuqi
authors: W
authors: Song
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.|Heilongjiang Provincial Key Laboratory of Infection and Immunity, Harbin Medical University, Harbin, China.
authors: Yujun
authors: Y
authors: Li
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.
authors: Ying
authors: Y
authors: Huang
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.
authors: Zheng
authors: Z
authors: Wu
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.
authors: Rui
authors: R
authors: Sun
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China.
authors: Chunping
authors: C
authors: Dong
authors: Wu Lien-Teh Institute, Department of Microbiology, Harbin Medical University, 157, Baojian Road, Nangang District, Harbin, 150081, China. fengminzhang@ems.hrbmu.edu.cn.|Heilongjiang Provincial Key Laboratory of Infection and Immunity, Harbin Medical University, Harbin, China. fengminzhang@ems.hrbmu.edu.cn.
authors: Fengmin
authors: F
authors: Zhang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002439:Cefotaxime / Q000494:pharmacology*; D019818:Clavulanic Acid / Q000494:pharmacology; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011807:Quinolizines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D004365:Drugs, Chinese Herbal; D029968:Escherichia coli Proteins; D044950:Flavanones; D011807:Quinolizines; D012333:RNA, Messenger; D019818:Clavulanic Acid; C006680:baicalein; C412613:CTX-M-9 protein, E coli; C055184:beta-lactamase TEM-3; D001618:beta-Lactamases; D002439:Cefotaxime; D000093842:Matrines
keywords: Baicalein; CTX-M-1 gene; Extended- spectrum β- lactamases; Klebsiella pneumoniae; Synergistic antibacterial action