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枸橼酸苦木水提取物对多重耐药痢疾志贺菌和福氏志贺菌中ompC和ompF的差异表达,改变其对β-内酰胺类抗生素的敏感性。

Differential expression of ompC and ompF in multidrug-resistant Shigella dysenteriae and Shigella flexneri by aqueous extract of Aegle marmelos, altering its susceptibility toward beta-lactam antibiotics.

作者信息

Raja Subramaniya Bharathi, Murali Malliga Raman, Devaraj Sivasitambaram Niranjali

机构信息

Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu 600025, India.

出版信息

Diagn Microbiol Infect Dis. 2008 Jul;61(3):321-8. doi: 10.1016/j.diagmicrobio.2008.02.006. Epub 2008 Mar 21.

Abstract

Steadily increasing resistance among Shigella to beta-lactams, aminoglycosides, and tetracycline has compromised the utility of these commonly used antimicrobial agents. Also, undesirable side effects of certain antibiotics have triggered immense interest in search of alternative therapies using medicinal plants. One such medicinal plant used since ancient times to cure diarrhea is Aegle marmelos. The present study exemplifies the susceptibility of beta-lactam-resistant Shigella dysenteriae and Shigella flexneri toward beta-lactam antibiotics, when grown in the presence of aqueous extract of A. marmelos (AEAM), by altering porin channels. This was demonstrated by antibiotic sensitivity test using disc diffusion method and MIC test. Susceptibility toward beta-lactam antibiotic is associated with changes in outer membrane porins OmpC (approximately 42 kDa) and OmpF (approximately 38 kDa) and cytosolic proteins of approximately 26 kDa, OmpR, a transcriptional regulator. Expression of ompF is increased in S. dysenteriae and S. flexneri grown in the presence of AEAM due to down-regulation of ompR, which is conformed by reverse transcriptase polymerase chain reaction. In conclusion, AEAM influences susceptibility of beta-lactam-resistant Shigella toward beta-lactam antibiotics by altering porin channels. Hence, AEAM along with beta-lactam can be used for treatment of multidrug-resistant Shigella.

摘要

志贺氏菌对β-内酰胺类、氨基糖苷类和四环素的耐药性持续增加,已影响了这些常用抗菌药物的效用。此外,某些抗生素的不良副作用引发了人们对使用药用植物替代疗法的极大兴趣。一种自古以来就用于治疗腹泻的药用植物是枸橼酸苦木。本研究通过改变孔蛋白通道,例证了耐β-内酰胺的痢疾志贺氏菌和福氏志贺氏菌在枸橼酸苦木水提取物(AEAM)存在下生长时对β-内酰胺类抗生素的敏感性。这通过使用纸片扩散法和最低抑菌浓度(MIC)试验的抗生素敏感性试验得以证明。对β-内酰胺类抗生素的敏感性与外膜孔蛋白OmpC(约42 kDa)和OmpF(约38 kDa)以及约26 kDa的胞质蛋白、转录调节因子OmpR的变化有关。由于ompR的下调,在AEAM存在下生长的痢疾志贺氏菌和福氏志贺氏菌中ompF的表达增加,这通过逆转录聚合酶链反应得以证实。总之,AEAM通过改变孔蛋白通道影响耐β-内酰胺志贺氏菌对β-内酰胺类抗生素的敏感性。因此,AEAM与β-内酰胺类药物联合可用于治疗多重耐药志贺氏菌。

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