万古霉素耐药肠球菌自20世纪80年代后期被发现以来,已逐渐发展成为重要的医院感染病原菌。此类耐药肠球菌携带的万古霉素耐药基因簇编码产物可催化合成与万古霉素、替考拉宁等糖肽类抗生素亲和力极低的细胞壁前体导致耐药。目前已在肠球菌中发现的万古霉素耐药基因簇根据基因序列及构成不同分为9个型别;依据它们编码的连接酶合成产物不同又可分为D-Ala:D-Lac连接酶基因簇(VanA、VanB、VanD及VanM型)和D-Ala:D-Ser连接酶基因簇(VanC、VanE、VanG、VanL和VanN型)。这些耐药基因簇介导的耐药水平及其传播模式各有特点。文章综述了肠球菌中万古霉素耐药基因簇的类型、基因构成及传播特性。
Vancomycin resistant enterococci has become an important nosocomial pathogen since it is discovered in late 1980s. The products, encoded by vancomycin resistant gene cluster in enterococci, catalyze the synthesis of peptidoglycan precursors with low affinity with glycopeptide antibiotics including vancomycin and teicoplanin and lead to resistance. These vancomycin resistant gene clusters are classified into nine types according to their gene sequences and organization, or D-Ala:D-Lac (VanA, VanB, VanD and VanM) and D-Ala:D-Ser (VanC, VanE, VanG, VanL and VanN) ligase gene clusters based on the differences of their encoded ligases. Moreover, these gene clusters are characterized by their different resistance levels and infection models. In this review, we summarize the classification, gene organization and infection model of vancomycin resistant gene cluster in Enterococcus spp.
[1] Fisher K, Phillips C. The ecology, epidemiology and virulence of Enterococcus . Microbiology , 2009, 155(Pt 6): 1749-1757.
[2] Levine DP. Vancomycin: a history. Clin Infect Dis , 2006, 42(Suppl 1): S5-S12.
[3] Bonten MJ, Willems R, Weinstein RA. Vancomycin-resistant enterococci: why are they here, and where do they come from? Lancet Infect Dis , 2001, 1(5): 314-325.
[4] Courvalin P. Vancomycin resistance in gram-positive cocci. Clin Infect Dis , 2006, 42(Suppl. 1): S25-S34.
[5] Boyd DA, Willey BM, Fawcett D, Gillani N, Mulvey MR. Molecular characterization of Enterococcus faecalis N06-0364 with low-level vancomycin resistance harboring a novel D-Ala-D-Ser gene cluster, vanL . Antimicrob Agents Chemother , 2008, 52(7): 2667-2672.
[6] Xu XG, Lin DF, Yan GQ, Ye XY, Wu S, Guo Y, Zhu DM, Hu FP, Zhang YY, Wang F, Jacoby GA, Wang MG. vanM , a new glycopeptide resistance gene cluster found in Enterococcus faecium . Antimicrob Agents Chemother , 2010, 54(11): 4643-4647.
[7] Lebreton F, Depardieu F, Bourdon N, Fines-Guyon M, Berger P, Camiade S, Leclercq R, Courvalin P, Cattoir V. D-Ala-d-Ser VanN-type transferable vancomycin resistance in Enterococcus faecium . Antimicrob Agents Chemother , 2011, 55(10): 4606-4612.
[8] McKessar SJ, Berry AM, Bell JM, Turnidge JD, Paton JC. Genetic characterization of vanG , a novel vancomycin resistance locus of Enterococcus faecalis . Antimicrob Agents Chemother , 2000, 44(11): 3224-3228.
[9] Ramos S, Chafsey I, Silva N, Hébraud M, Santos H, Capelo-Martinez JL, Poeta P, Igrejas G. Effect of vancomycin on the proteome of the multiresistant Enterococcus faecium SU18 strain. J Proteomics , 2015, 113: 378-387.
[10] Bugg TDH, Wright GD, Dutka-Malen S, Arthur M, Courvalin P, Walsh CT. Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. Biochemistry , 1991, 30(43): 10408-10415.
[11] Evers S, Reynolds PE, Courvalin P. Sequence of the vanB and ddl genes encoding D-alanine: D-lactate and D-alanine: D-alanine ligases in vancomycin-resistant Enterococcus faecalis V583. Gene, 1994, 140(1): 97-102.
[12] Depardieu F, Reynolds PE, Courvalin P. VanD-type vancomycin-resistant Enterococcus faecium 10/96A. Antimicrob Agents Chemother , 2003, 47(1): 7-18.
[13] Dutka-Malen S, Molinas C, Arthur M, Courvalin P. Sequence of the vanC gene of Enterococcus gallinarum BM4174 encoding a D-alanine: D-alanine ligase-related protein necessary for vancomycin resistance. Gene , 1992, 112(1): 53-58.
[14] Patiño LA, Courvalin P, Perichon B. vanE gene cluster of vancomycin-resistant Enterococcus faecalis BM4405. J Bacteriol , 2002, 184(23): 6457-6464.
[15] Arthur M, Molinas C, Depardieu F, Courvalin P. Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J Bacteriol , 1993, 175(1): 117-127.
[16] Leclercq R, Derlot E, Duval J, Courvalin P. Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium . N Engl J Med , 1988, 319(3): 157-161.
[17] Handwerger S, Skoble J. Identification of chromosomal mobile element conferring high-level vancomycin resistance in Enterococcus faecium . Antimicrob Agents Chemother , 1995, 39(11): 2446-2453.
[18] Quintiliani R Jr, Courvalin P. Conjugal transfer of the vancomycin resistance determinant vanB between enterococci involves the movement of large genetic elements from chromosome to chromosome. FEMS Microbiol Lett , 1994, 119(3): 359-363.
[19] Rice LB, Carias LL, Donskey CL, Rudin SD. Transferable, plasmid-mediated vanB -type glycopeptide resistance in Enterococcus faecium . Antimicrob Agents Chemother , 1998, 42(4): 963-964.
[20] Moura TM, Cassenego AP, Campos FS, Ribeiro AM, Franco AC, d'Azevedo PA, Frazzon J, Frazzon AP. Detection of van
