抗生素耐药性一直是细菌病害防治的难题,药物外排泵过量表达是细菌耐药性形成的重要机制之一。在革兰氏阴性细菌中,RND(Resistance-nodulation-cell division)家族外排泵在耐药性中发挥着重要作用,近年来的研究表明,依赖于小分子信号物质进行调控的群体感应系统与RND外排泵家族之间存在紧密的相互作用关系。本文在介绍RND家族外排泵的结构、转运机理和群体感应系统的类型及调控方式的基础上,剖析了群体感应系统对RND外排泵的调控机理以及RND外排泵对群体感应系统信号分子转运的影响。深入研究RND家族外排泵与群体感应系统之间的相互依赖、相互制约关系有利于阐明RND家族外排泵的调控机理,并有可能为克服微生物耐药性问题提供新的思路。
Antibiotic resistance has become a serious concern in treatment of bacterial infections. Overexpression of efflux pump is one of the important mechanisms in antibiotic resistance. In Gram negative bacteria, RND (Resistance-nodulation-cell division) superfamily efflux pump plays a vital important role in antibiotics resistance. Recent research progress unveils an intriguing interrelationship between RND efflux pump and the bacterial quorum sensing system, whose regulation is dependent on small signal molecules. This article reviews the latest findings on the structure and transport mechanism of RND efflux pump, as well as the general features and regulatory mechanisms of quorum sensing, with a special focus on the role and mechanism of quorum sensing system in regulation of RND efflux pump, and the influence of efflux pump on quorum sensing signal transportation. Further investigation of the interrelationship between RND efflux pumps and the bacterial quorum sensing systems is critical for elucidation of the regulatory mechanisms that govern the expression of the RND efflux pumps genes, and may also provide useful clues to overcome the efflux pump mediated antibiotic resistance.
[1] Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJV. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol , 2015, 13(1): 42-51.
[2] Li XZ, Plésiat P, Nikaido H. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev , 2015, 28(2): 337-418.
[3] Blair JMA, Piddock LJV. Structure, function and inhibition of RND efflux pumps in Gram-negative bacteria: an update. Curr Opin Microbiol , 2009, 12(5): 512-519.
[4] Roggiani M, Dubnau D. ComA, a phosphorylated response regulator protein of Bacillus subtilis , binds to the promoter region of srfA . J Bacteriol , 1993, 175(10): 3182-3187.
[5] Eberl L, Winson MK, Sternberg C, Stewart GSAB, Christiansen G, Chhabra SR, Bycroft B, Williams P, Molin S, Givskov M. Involvement of N -acyl-L-homoserine lactone autoinducers in controlling the multicellular behaviour of Serratia liquefaciens . Mol Microbiol , 1996, 20(1): 127-136.
[6] Marketon MM, Glenn SA, Eberhard A, González JE. Quorum sensing controls exopolysaccharide production in Sinorhizobium meliloti . J Bacteriol , 2003, 185(1): 325-331.
[7] Deng YY, Schmid N, Wang C, Wang JH, Pessi G, Wu DH, Lee J, Aguilar C, Ahrens CH, Chang CQ, Song HW, Eberl L, Zhang LH. Cis-2-dodecenoic acid receptor RpfR links quorum-sensing signal perception with regulation of virulence through cyclic dimeric guanosine monophosphate turnover. Proc Natl Acad Sci USA , 2012, 109(38): 15479-15484.
[8] Zhang LH, Murphy PJ, Kerr A, Tate ME. Agrobacterium conjugation and gene regulation by N -acyl-L-homoserine lactones. Nature , 1993, 362(6419): 446-448.
[9] Davies DG, Parsek MR, Pearson JP, Iglewski BH, Costerton JW, Greenberg EP. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science , 1998, 280(5361): 295-298.
[10] Daury L, Orange F, Taveau JC, Verchère A, Monlezun L, Gounou C, Marreddy RKR, Picard M, Broutin I, Pos KM, Lambert O. Tripartite assembly of RND multidrug efflux pumps. Nat Commun , 2016, 7: 10731.
[11] Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature , 2006, 443(7108): 173-179.
[12] Husain F, Bikhchandani M, Nikaido H. Vestibules are part of the substrate path in the multidrug efflux transporter AcrB of Escherichia coli . J Bacteriol , 2011, 193(20): 5847-5849.
[13] Anes J, McCusker MP, Fanning S, Martins M. The ins and outs of RND efflux pumps in Escherichia coli . Front Microbiol , 2015, 6: 587.
[14] Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. Contribution of the MexX-MexY-OprM efflux system to intrinsic resistance in Pseudomonas aeruginosa . Antimicrob Agents Chemother , 2000, 44(9): 2242-2246.
[15] Mine T, Morita Y, Kataoka A, Mizushima T, Tsuchiya T. Expression in Escherichia coli of a new multidrug efflux pump, MexXY, from Pseudomonas aeruginosa . Antimicrob Agents Chemother , 1999, 43(2): 415-417.
[16] Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa : evidence for involvement of an efflux operon. J Bacteriol , 1993, 175(22): 7363-7372.
[17] Koronakis V, Sharff A, Koronakis E, Luisi B, Hughes C. Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. Nature , 2000, 405(6789): 914-919.
[18] Dreier J, Ruggerone P. Interaction of antibacterial compounds with RND efflux pumps in Pseudomonas aeruginosa . Front Microbiol , 2015, 6: 660.
[19] Lister PD, Wolter DJ, Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa : clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev , 2009, 22(4): 582-610.
[20] Buroni S, Matthijs N, Spadaro F, Van Acker H, Scoffone VC, Pasca MR, Riccardi G, Coenye T. Differential roles of RND efflux pumps in antimicrobial drug resistance of sessile and plankton
