摘要
近年来抗菌药物的广泛使用,导致细菌耐药性问题日益严重,耐药菌所致的感染给人类健康及畜禽生产带来巨大威胁,随着高通量测序技术的迅速发展,细菌转录组学的研究可帮助人们探究细菌耐药前后发生差异表达的基因以及筛选出具有调控作用的非编码RNA。本文以细菌耐药性的产生机制和调控机制为出发点,从转录组水平探讨耐药细菌中外排泵系统、二元调控系统、代谢途径相关基因的差异表达情况和非编码RNA对细菌外排泵系统、细胞膜通透性和生物被膜的调控机制,以期为细菌耐药性研究奠定基础。
Recently, the widespread use of antimicrobial agents has led to an increasingly serious problem in bacterial resistance. The infection caused by drug-resistant bacteria poses a great threat to human health and the production of livestock and poultry. With the rapid development of high-throughput sequencing technology, the study of bacterial transcriptome can help us to explore the differential expression genes before and after bacterial resistance and to screen sRNA with regulatory function. This paper is based on the mechanism of bacterial resistance generation and regulation, inquire into differential expression of genes related to efflux pump system, Two-Component Regulatory System and metabolize pathway of drug-resistant bacteria. This paper also discusses the regulation mechanism of sRNA on efflux pump system, membrane permeability and biofilm of bacteria, which will provide a foundation for the study in bacterial resistance.
引文
[1]张春兰,秦孜娟,王桂芝,等.转录组与RNA-Seq技术[J].生物技术通报,2012(12):51-56.
[2] WANG Z, GERSTEIN M, SNYDER M. RNA-Seq:a revo?lutionary tool for transcriptomics[J]. Nat Rev Genet,2009, 10(1):57-63.
[3] BUSH K, GACOBY G A, MEDEIROS A A. A functional classfication scheme forβ-lactamases and its correlation with molecular structure[J]. Antimicrob Agents Chemoth?er, 1995, 39(6):1211-1233.
[4]董毅.大环内酯类抗生素的研究进展[J].国外医药·合成药生化药制剂分册,2001,22(3):134-136.
[5]雷连成,韩文瑜,段艳.大肠杆菌耐药性抑制剂作用机制的初步研究[J].中国兽药杂志,2004,38(2):18-21.
[6] POOLE K. Multidrug resistance in Gram-negative bacteria[J]. Curr Opin Microbiol, 2001, 4(5):500-508.
[7]石廷玉,邓万燕,谢建平.致病菌生物被膜形成的调节机制及潜在的药物靶标[J].药学学报,2012,47(2):135-143.
[8] DU D, VAN VEEN H W, LUISI B F. Assembly and oper?ation of bacterial tripartite multidrug efflux pumps[J].Trends Microbiol, 2015, 23(5):311-319.
[9]冯帅.沙门菌体内耐药诱导模型的建立及体外诱导耐药菌RNA-seq分析[D].合肥:安徽农业大学,2015.
[10]刘建华,付赛赛,王亚云,等.环丙沙星诱导对临床耐药菌株主动外排基因转录的影响[J].畜牧兽医学报,2017,48(9):1753-1760.
[11]张传珍,常满霞,杨磊,等. MarA和SoxS共同调节大肠杆菌K12外排泵AcrAB-TolC的表达[J].中国兽医学报,2017,37(12):2370-2377.
[12] ARABESTANI M R, RAJABPOUR M, YOUSEFI MASHOUF R, et al. Expression of efflux pump MexABOprM and OprD of Pseudomonas aeruginosa strains isolat?ed from clinical samples using qRT-PCR[J]. Arch Iran Med, 2015, 18(2):102-108.
[13]潘亚萍.外排泵MexAB-OprM在铜绿假单胞菌对碳青霉烯类抗生素耐药机制的研究[D].合肥:安徽医科大学,2017.
[14] LI X Z, PLESIATl P, NIKAIDO H. The challenge of ef?flux-mediated antibiotic resistance in Gram-negative bacte?ria[J]. Clin Microbiol Rev. 2015, 28(2):337-418.
[15] HALL C W, ZHANG L, MAH T F. PA3225 Is a Tran?scriptional Repressor of Antibiotic Resistance Mechanisms in Pseudomonas aeruginosa[J]. Antimicrob Agents Che?mother, 2017, 61(8):e02114-16.
[16]王红红.布鲁氏菌TCS TceSR和TcfSR的蛋白组学和转录组学分析[D].石河子:石河子大学,2017.
[17]汪浙炯. PhoQ/PhoP与外膜蛋白OprH在铜绿假单胞菌对氨基糖甙类抗生素耐药性中的相互关系和作用机制[D].杭州:浙江大学,2011.
[18] KATO A, LATIFI T, GROISMAN E A. Closing the loop:the PmrA/PmrB two-component system negatively controls expression of its posttranscriptional activator PmrD[J].Proc Natl Acad Sci, 2003, 100(8):4706-4711.
[19]张旭,乔培壮,张学斌,等.江苏、山东部分地区禽致病性大肠杆菌流行病学调查[J].中国家禽,2017,39(6):74-76.
[20]李明举,李渤南,由佳,等.胶东地区肉鸡大肠杆菌耐药性研究[J].中国家禽,2018,40(10):62-64.
