Ⅱa类乳酸菌细菌素的分类

赵爱珍，徐兴然

(西南大学药学院，重庆 400715)

摘 要：Ⅱa类乳酸菌细菌素是一类抗菌肽，具有作为食品防腐剂或者抗菌药物的潜力。本文综合30种Ⅱa类乳酸菌细菌素的研究概况，从天然产生菌、产生途径、抗微生物功能、抗菌谱、作用方式和结构特征等方面对其进行分类综述，为全面了解该类细菌素提供一定的参考。

关键词：Ⅱa类细菌素；乳酸菌；抗菌肽；分类

Classi?cation of Class Ⅱa Bacteriocins from Lactic Acid Bacteria

ZHAO Ai-zhen，XU Xing-ran

(College of Pharmaceutical Science, Southwest University, Chongqing 400715, China)

Abstract：Class Ⅱa bacteriocins produced by lactic acid bacteria (LAB) belong to antimicrobial peptides and have potential applications as food preservatives or therapeutic agents. In this article, 30 class Ⅱa bacteriocins are classi?ed into different groups according to native bacteria, production methods, antimicrobial functions, antibacterial spectrum, action modes and structures.

Key words：class Ⅱa bacteriocin；lactic acid bacteria；antimicrobial peptide；classi?cation

中图分类号：TS201.3 文献标志码：A 文章编号：1002-6630(2013)17-0356-05

doi:10.7506/spkx1002-6630-201317074

乳酸菌细菌素是指由乳酸菌产生的具有抗微生物活性的多肽或者蛋白质，亦包含通过其他途径获得的相同或相似结构的抗菌物质[1]。乳酸菌细菌素主要包括三大类：Ⅰ类细菌素为含有修饰氨基酸的多肽；Ⅱ类细菌素为不含修饰氨基酸的多肽；Ⅲ类细菌素为大分子质量蛋白质[2]。Ⅱ类细菌素包括4个亚类，其中Ⅱa类细菌素为目前成员最多、研究比较深入的一类细菌素[1-2]。Ⅱa类乳酸菌细菌素具有作为食品防腐剂或者抗菌药物的应用潜力，本文从天然产生菌、产生途径、抗微生物功能、抗菌谱、作用方式、结构特征等六方面对该类细菌素进行再分类，对于全面了解该类细菌素具有重要意义。

1 根据天然产生菌进行分类

乳酸菌是一类能够发酵糖产生大量乳酸的革兰氏阳性细菌的统称，包括多个菌属[3]。根据天然产生菌，将Ⅱa类乳酸菌细菌素分为以菌属命名的细菌素。目前已经检测到30多种Ⅱa类乳酸菌细菌素，其中乳杆菌、片球菌、明串珠菌、肉食杆菌和肠球菌是主要产生菌属。表1列举出它们产生的30种细菌素，Enterocin A/Enterocin 81、Enterocin CRL35/Mundticin KS、Enterocin P、Bacteriocin T8/Hiracin JM79、Bacteriocin E 50-52等11种细菌素属于肠球菌细菌素[1,4-13]；Sakacin A/Curvacin A、Sakacin P/Bavaricin A、Bacteriocin L-1077、Pediocin PA-1/AcH、Plantaricin C19等9种细菌素属于乳杆菌细菌素[1,14-17]；Divercin V41、Piscicolin 126/Piscicocin V1a、Carnobacteriocin BM1/PiscicocinV1b等6种细菌素属于肉食杆菌细菌素[1,18-19]；Leucocin A、Mesentericin Y105/Mesenterocin 52A等3种细菌素属于明串珠菌细菌素[1,20-21]；Pediocin PA-1/AcH、Penocin A等2种细菌素属于片球菌细菌素[1,16,22-24]。从表1可以看出，同一菌属可以产生不同的细菌素，不同菌属也可产生相同的细菌素，如Pediocin PA-1既属于片球菌细菌素又属于乳杆菌细菌素；就同一菌属而言，不同种细菌可以产生相同或者不同的细菌素，同种细菌也可以产生不同或者相同的细菌素。

2 根据产生途径进行分类

根据产生途径，将Ⅱa类乳酸菌细菌素分为天然细菌素、化学合成细菌素和重组细菌素。

天然细菌素是乳酸菌在其代谢过程中通过核糖体机制合成的、并被分泌到细胞外的抗菌物质，可通过体外发酵培养、无细胞发酵上清液的制备、细菌素的纯化等步骤获得天然细菌素。在通常情况下，天然细菌素产生量及得率均较低，但可以通过优化培养条件、改善纯化方法来提高产量和得率[25-26]。

化学合成细菌素是根据天然细菌素的氨基酸序列及结构特征通过固相法合成的，合成量及纯度较易控制，但是成本相对较高。目前已化学合成细菌素Pediocin PA-1、Sakacin P、Curvacin A、Leucocin A、Mesentericin Y 105等，可以替代天然细菌素进行抗菌作用方面的研究[27-29]。

重组细菌素是通过基因工程技术而获得，其合成是可控制的。目前适于Ⅱa类乳酸菌细菌素进行异源表达的系统包括乳酸菌表达系统、大肠杆菌表达系统和酵母表达系统；表达方式分为单独表达和融合表达。细菌素融合表达后的产物为融合蛋白或者融合多肽，可通过蛋白酶切除融合标签后得到重组细菌素。目前利用乳酸菌表达系统获得的重组细菌素包括Mundticin KS、Penocin A、

Pediocin PA-1、Sakacin P、Carnobacteriocin B2、Mesentericin Y105、Enterocin P、Divercin V41、Hiracin JM79、Enterocin A、Leucocin C等[9,24,30-37]；利用大肠杆菌表达系统获得的重组细菌素包括Mesentericin Y105、Pediocin PA-1、Divercin V41、Piscicolin 126、Enterocin A、Enterocin P、Carnobacteriocin B2、Carnobacteriocin BM1、Sakacin P等[32,38-42]；利用酵母表达系统获得的重组细菌素包括Hiracin JM79、Plantaricin 423、Pediocin PA-1、Enterocin P、Enterocin A等[35,43-46]。

3 根据抗微生物功能进行分类

Ⅱa类乳酸菌细菌素属于抗菌肽，抗细菌是该类细菌素的最主要功能，见表2。Enterocin CRL35除具有抗细菌功能外[8-9]，还能够抑制疱疹病毒-Ⅰ(HSV-1)和疱疹病毒-Ⅱ(HSV-2)的繁殖[47]。因此，根据抗微生物功能，将Ⅱa类乳酸菌细菌素分为抗细菌细菌素和抗病毒细菌素。Pediocin PA-1等所有细菌素均属于抗细菌细菌素，Enterocin CRL35则又属于抗病毒细菌素。随着研究的广泛开展，抗病毒细菌素的家族成员可能会增加。

4 根据抗菌谱进行分类

乳酸菌为一类革兰氏阳性细菌，其产生的细菌素主要表现为抗革兰氏阳性细菌的作用。研究表明绝大多数Ⅱa类乳酸菌细菌素仅对乳酸菌、李斯特菌等革兰氏阳性细菌表现抗菌活性[1,4,26,48-50]；某些细菌素如还对葡萄球菌、梭菌等其他革兰氏阳性细菌表现抗菌活性[10,15,22,51]；但是极少数细菌素对大肠杆菌、沙门氏菌等革兰氏阴性细菌也表现抗菌活性[10,15,52]。表2列举出11种细菌素的抗菌活性。将仅对革兰氏阳性细菌表现活性的细菌素称为窄谱细菌素；对革兰氏阳性细菌和革兰氏阴性细菌的细菌素均表现活性的细菌素称为广谱细菌素。依据此分类方法，Bacteriocin L-1077、Bacteriocin E 50-52属于广谱细菌素，其他28种细菌素属于窄谱细菌素。

表 2 Ⅱa类乳酸菌细菌素对指示菌的活性

Table 2 Activity of class IIa bacteriocins against indicator strains

注：Ped PA-1. Pediocin PA-1；Leu A. Leucocin A；Sak P. Sakacin P；Cur A. Curvacin A；Ent A. Enterocin A；Ent CRL35. Enterocin CRL35；Mes Y105. Mesentericin Y105；Dvn V41. Divercin V41；Pis 126. Piscicolin 126；Bac E 50-52. Bacteriocin E 50-52；Bac L-1077. Bacteriocin L-1077；＋. 具有抗菌活性；－. 不具有抗菌活性。

5 根据作用方式进行分类

Ⅱa类乳酸菌细菌素以敏感性细菌的细胞膜为靶目标，作用后影响其通透性，通过抑制细菌生长或者杀死细菌而发挥抗菌作用。根据作用方式，将Ⅱa类乳酸菌细菌素分为抑菌细菌素和杀菌细菌素两类。表3列举了13种Ⅱa类乳酸菌细菌素对敏感性菌株的作用方式，其中Plantaricin C19[17]、Leucocin A[20]、Mesenterocin 52A[28]等3种细菌素表现抑菌方式，属于抑菌细菌素；Enterocin A[4]、Enterocin P[7]、Bacteriocin T8[11]、Sakacin A[14]、PiscicocinV1b[19]、Pediocin PA-1[53]、Enterocin CRL35[54]、Piscicolin 126[55]、Divergicin M35[56]、Piscicocin CS526[57]等10种细菌素表现为杀菌方式，属于杀菌细菌素。由于研究人员没有对其他17种细菌素进行相关研究，所以此处不能列出其具体的作用方式，但是归属于抑菌细菌素或者杀菌细菌素。新发现的细菌素或者其他菌属的细菌素也可以依据作用方式进行归类。

表 3 Ⅱa类乳酸菌细菌素对敏感性细菌的作用方式

Table 3 Action modes of class IIa bacteriocins against sensitive strains

6 根据结构特征进行分类

依据相似的氨基酸序列，Ⅱa类乳酸菌细菌素的肽链可大致分为两个结构区：亲水性的、阳离子的和高度保守的N-端区和两亲性/疏水性的低度保守的C-端区[27]。细菌素的N-端区含有共有序列，是影响其抗菌活性的关键因素。根据所含共有序列的不同，将Ⅱa类乳酸菌细菌素分为含YGNGL的细菌素和含YGNGV的细菌素。Plantaricin C19、Piscicocin CS526、Hiracin JM79等8种细菌素属于含YGNGL的细菌素；Pediocin PA-1、Enterocin A、Divercin V41等其他22种细菌素属于含YGNGV的细菌素。

根据氨基酸序列是否含有半胱氨酸(C)，将Ⅱa类乳酸菌细菌素分为含半胱氨酸细菌素和不含半胱氨酸细菌素。就列出的30种细菌素而言，仅Bacteriocin L-1077归属于不含半胱氨酸细菌素[16]，其他29种细菌素均归属含半胱氨酸细菌素。Bacteriocin E 50-52含有6个半胱氨酸[10]，目前还没有关于确定其含有3个二硫键的报道。Pediocin PA-1、Enterocin A、Divercin V41等8种细菌素含有4个半胱氨酸，形成1个N-端区二硫键和1个C-端区二硫键[1,13,26]。Enterocin P、Leucocin A、Sakacin P等20种细菌素含有2个半胱氨酸，形成1个N-端区二硫键[1,7]。

7 结 语

本文以30种Ⅱa类乳酸菌细菌素作为基础，对Ⅱa类乳酸菌细菌素进行分类总结。根据天然产生菌，可将Ⅱa类乳酸菌细菌素分为以菌属命名的细菌素；根据产生途径，可将其分为天然细菌素、化学合成细菌素和重组细菌素；根据抗微生物功能，可将其分为抗细菌细菌素和抗病毒细菌素；根据抗菌谱，可将其分为窄谱细菌素和广谱细菌素；根据作用方式，可将其分为杀菌细菌素和抑菌细菌素；根据N-端区共有序列的差异，可将其分为含YGNGV的细菌素和含YGNGL的细菌素；根据半胱氨酸的含量，可将其分为含半胱氨酸细菌素和不含半胱氨酸细菌素。

参考文献：

[1] DRIDER D, REBUFFAT S. Prokaryotic antimicrobial peptides: from genes to applications[M]. New York: Springer Science, LLC, 2011.

[2] CINTAS L M, HERRANZ C, HERNÁNDEZ P E, et al. Review: bacteriocins of lactic acid bacteria[J]. Food Sci Tech Int, 2001, 7(4): 281-305.

[3] STILES M E, HOLZAPFEL W H. Lactic acid bacteria of foods and their current taxonomy[J]. Int J Food Microbiol, 1997, 36(1): 1-29.

[4] ENNAHAR S, DESCHAMPS N. Anti-Listeria effect of enterocin A, produced by cheese-isolated Enterococcus faecium EFM01, relative to other bacteriocins from lactic acid bacteria[J]. J Appl Microbiol, 2000, 88(3): 449-457.

[5] ENNAHAR S, AOUDE-WERNER D, ASSOBHEI O, et al. Antilisterial activity of enterocin 81, a bacteriocin produced by Enterococcus faecium WHE 81 isolated from cheese[J]. J Appl Microbiol, 1998, 85(3): 521-526.

[6] ENNAHAR S, ASOU Y, ZENDO T, et al. Biochemical and genetic evidence for production of enterocins A and B by Enterococcus faecium WHE 81[J]. Int J Food Microbiol, 2001, 70(3): 291-301.

[7] CINTAS L M, CASAUS P, HAVARSTEIN L S, et al. Biochemical and genetic characterization of enterocin P, a novel sec-dependent bacteriocin from Enterococcus faecium P13 with a broad antimicrobial spectrum[J]. Appl Environ Microbiol, 1997, 63(11): 4321-4330.

[8] SAAVEDRA L, MINAHK C, de RUIZ HOLGADO A P, et al. Enhancement of the enterocin CRL35 activity by a synthetic peptide derived from the NH2-terminal sequence[J]. Antimicrob Agents Chemother, 2004, 48(7): 2778-2781.

[9] KAWAMOTO S, SHIMA J, SATO R, et al. Biochemical and genetic characterization of mundticin KS, an antilisterial peptide produced by Enterococcus mundtii NFRI 7393[J]. Appl Environ Microbiol, 2002, 68(8): 3830-3840.

[10] SVETOCH E A, ERUSLANOV B V, PERELYGIN V V, et al. Diverse antimicrobial killing by Enterococcus faecium E 50-52 bacteriocin[J]. J Agric Food Chem, 2008, 56(6): 1942-1948.

[11] de KWAADSTENIET M, FRASER T, van REENEN C A, et al. Bacteriocin T8, a novel class Ⅱa sec-dependent bacteriocin produced by Enterococcus faecium T8, isolated from vaginal secretions of children infected with human immunodeficiency virus[J]. Appl Environ Microbiol, 2006, 72(7): 4761-4766.

[12] SÁNCHEZ J, DIEP D B, HERRANZ C, et al. Amino acid and nucleotide sequence, adjacent genes, and heterologous expression of hiracin JM79, a sec-dependent bacteriocin produced by Enterococcus hirae DCH5, isolated from Mallard ducks (Anas platyrhynchos)[J]. FEMS Microbiol Lett, 2007, 270(2): 227-236.

[13] HIMENO K, FUJITA K, ZENDO T, et al. Identification of enterocin NKR-5-3C, a novel class Ⅱa bacteriocin produced by a multiple bacteriocin producer, Enterococcus faecium NKR-5-3[J]. Biosci Biotechnol Biochem, 2012, 76(6): 1245-1247.

[14] SCHILLINGER U, LÜCKE F K. Antibacterial activity of Lactobacillus sake isolated from meat[J]. Appl Environ Microbiol, 1989, 55(8): 1901-1906.

[15] SVETOCH E A, ERUSLANOV B V, LEVCHUK V P, et al. Isolation of Lactobacillus salivarius 1077 (NRRL B-50053) and characterization of its bacteriocin, including the antimicrobial activity spectrum[J]. Appl Environ Microbiol, 2011, 77(8): 2749-2754.

[16] ENNAHAR S, AOUDE-WERNER D, SOROKINE O, et al. Production of pediocin AcH by Lactobacillus plantarum WHE 92 isolated from cheese[J]. Appl Environ Microbiol, 1996, 62(12): 4381-4387.

[17] ATRIH A, REKHIF N, MOIR A J, et al. Mode of action, purification and amino acid sequence of plantaricin C19, an anti-Listeria bacteriocin produced by Lactobacillus plantarum C19[J]. Int J Food Microbiol, 2001, 68(1/2): 93-104.

[18] JACK R W, WAN J, GORDON J, et al. Characterization of the chemical and antimicrobial properties of piscicolin 126, a bacteriocin produced by Carnobacterium piscicola JG126[J]. Appl Environ Microbiol, 1996, 62(8): 2897-2903.

[19] BHUGALOO-VIAL P, DOUSSET X, METIVIER A, et al. Purification and amino acid sequences of piscicocins V1a and V1b, two class IIa bacteriocins secreted by Carnobacterium piscicola V1 that display significantly different levels of specific inhibitory activity[J]. Appl Environ Microbiol, 1996, 62(12): 4410-4416.

[20] HASTINGS J W, STILES M E. Antibiosis of Leuconostoc gelidum isolated from meat[J]. J Appl Bacteriol, 1991, 70(2): 127-134.

[21] HECHARD Y, DERIJARD B, LETELLIER F, et al. Characterization and purification of mesentericin Y105, an anti-Listeria bacteriocin from Leuconostoc mesenteroides[J]. J Gen Microbiol, 1992, 138(12): 2725-2731.

[22] BENNIK M, SMID E J, GORRIS L. Vegetable-associated Pediococcus parvulus produces pediocin PA-1[J]. Appl Environ Microbiol, 1997, 63(5): 2074-2076.

[23] VIJAY SIMHA B, SOOD S K, KUMARIYA R, et al. Simple and rapid purification of pediocin PA-1 from Pediococcus pentosaceous NCDC 273 suitable for industrial application[J]. Microbiol Res, 2012, 167(9): 544-549.

[24] DIEP D B, GODAGER L, BREDE D, et al. Data mining and characterization of a novel pediocin-like bacteriocin system from the genome of Pediococcus pentosaceus ATCC 25745[J]. Microbiology, 2006, 152(6): 1649-1659.

[25] REHAIEM A, GUERRA N P, BELGACEM Z B, et al. Enhancement of enterocin A production by Enterococcus faecium MMRA and determination of its stability to temperature and pH[J]. Biochemical Engineering Journal, 2011, 56(1/2): 94-106.

[26] GUYONNET D, FREMAUX C, CENATIEMPO Y, et al. Method for rapid purification of class IIa bacteriocins and comparison of their activities[J]. Appl Environ Microbiol, 2000, 66(4): 1744-1748.

[27] FIMLAND G, BLINGSMO O R, SLETTEN K, et al. New biologically active hybrid bacteriocins constructed by combining regions from various pediocin-like bacteriocins: the C-terminal region is important for determining specificity[J]. Appl Environ Microbiol, 1996, 62(9): 3313-3318.

[28] JASNIEWSKI J, CAILLIEZ-GRIMAL C, YOUNSI M, et al. Fluorescence anisotropy analysis of the mechanism of action of mesenterocin 52A: speculations on antimicrobial mechanism[J]. Appl Microbiol Biotechnol, 2008, 81(2): 339-347.

[29] PAPATHANASOPOULOS M A, KRIER F, REVOL-JUNELLES A M, et al. Multiple bacteriocin production by Leuconostoc mesenteroides TA33a and other Leuconostoc/Weissella strains[J]. Curr Microbiol, 1997, 35(6): 331-335.

[30] AXELSSON L, KATLA T, BJØRNSLETT M, et al. A system for heterologous expression of bacteriocins in Lactobacillus sake[J]. FEMS Microbiol Lett, 1998, 168(1): 137-143.

[31] REVIRIEGO C, FERNANDEZ L, KUIPERS O P, et al. Enhanced production of pediocin PA-1 in wild nisin- and non-nisin-producing Lactococcus lactis strains of dairy origin[J]. International Dairy Journal, 2007, 17(5): 574-577.

[32] BIET F, BERJEAUD J M, WOROBO R W, et al. Heterologous expression of the bacteriocin mesentericin Y105 using the dedicated transport system and the general secretion pathway[J]. Microbiology, 1998, 144(10): 2845-2854.

[33] GUTIÉRREZ J, LARSEN R, CINTAS L M, et al. High-level heterologous production and functional expression of the sec-dependent enterocin P from Enterococcus faecium P13 in Lactococcus lactis[J]. Appl Microbiol Biotechnol, 2006, 72(1): 41-51.

[34] BERMÚDEZ-HUMARÁN L G, RIHAKOVA J, LANGELLA P, et al. Antimicrobial activity of divercin RV41 produced and secreted by Lactococcus lactis[J]. J Mol Microbiol Biotechnol, 2007, 13(4): 259-263.

[35] SÁNCHEZ J, BORRERO J, GÓMEZ-SALA B, et al. Cloning and heterologous production of Hiracin JM79, a Sec-dependent bacteriocin produced by Enterococcus hirae DCH5, in lactic acid bacteria and Pichia pastoris[J]. Appl Environ Microbiol, 2008, 74(8): 2471-2479.

[36] BORRERO J, JIMÉNEZ J J, GÚTIEZ L, et al. Protein expression vector and secretion signal peptide optimization to drive the production, secretion, and functional expression of the bacteriocin enterocin A in lactic acid bacteria[J]. J Biotechnol, 2011, 156(1): 76-86.

[37] WAN X, LI R, SARIS P E, et al. Genetic characterisation and heterologous expression of leucocin C, a class Ⅱa bacteriocin from Leuconostoc carnosum 4010[J]. Appl Microbiol Biotechnol, 2013, 97(8): 3509-3518.

[38] INGHAM A B, SPROAT K W, TIZARD M L, et al. A versatile system for the expression of nonmodified bacteriocins in Escherichia coli[J]. J Appl Microbiol, 2005, 98(3): 676-683.

[39] MOON G S, PYUN Y R, KIM W J. Expression and purification of a fusion-typed pediocin PA-1 in Escherichia coli and recovery of biologically active pediocin PA-1[J]. Int J Food Microbiol, 2006, 108(1): 136-140.

[40] KLOCKE M, MUNDT K, IDLER F, et al. Heterologous expression of enterocin A, a bacteriocin from Enterococcus faecium, fused to a cellulose-binding domain in Escherichia coli results in a functional protein with inhibitory activity against Listeria[J]. Appl Microbiol Biotechnol, 2005, 67(4): 532-538.

[41] JASNIEWSKI J, CAILLIEZ-GRIMAL C, GELHAYE E, et al. Optimization of the production and purification processes of carnobacteriocins Cbn BM1 and Cbn B2 from Carnobacterium maltaromaticum CP5 by heterologous expression in Escherichia coli[J]. J Microbiol Methods, 2008, 73(1): 41-48.

[42] CHEN H, TIAN F, LI S, et al. Cloning and heterologous expression of a bacteriocin sakacin P from Lactobacillus sakei in Escherichia coli[J]. Appl Microbiol Biotechnol, 2012, 94(4): 1061-1068.

[43] van REENEN C A, CHIKINDAS M L, van ZYL W H, et al. Characterization and heterologous expression of a class Ⅱa bacteriocin, plantaricin 423 from Lactobacillus plantarum 423, in Saccharomyces cerevisiae[J]. Int J Food Microbiol, 2003, 81(1): 29-40.

[44] BEAULIEU L, GROLEAU D, MIGUEZ C B, et al. Production of pediocin PA-1 in the methylotrophic yeast Pichia pastoris reveals unexpected inhibition of its biological activity due to the presence of collagen-like material[J]. Protein Expr Purif, 2005, 43(2): 111-125.

[45] GUTIÉRREZ J, CRIADO R, MARTÍN M, et al. Production of enterocin P, an antilisterial pediocin-like bacteriocin from Enterococcus faecium P13, in Pichia pastoris[J]. Antimicrob Agents Chemother, 2005, 49(7): 3004-3008.

[46] BORRERO J, KUNZE G, JIMÉNEZ J J, et al. Cloning, production, and functional expression of the bacteriocin enterocin A, produced by Enterococcus faecium T136, by the yeasts Pichia pastoris, Kluyveromyces lactis, Hansenula polymorpha, and Arxula adeninivorans[J]. Appl Environ Microbiol, 2012, 78(16): 5956-5961.

[47] WACHSMAN M B, FARIAS M E, TAKEDA E, et al. Antiviral activity of enterocin CRL35 against herpesviruses[J]. Int J Antimicrob Agents, 1999, 12(4): 293-299.

[48] RICHARD C, CAÑON R, NAGHMOUCHI K, et al. Evidence on correlation between number of disulfide bridge and toxicity of class IIa bacteriocins[J]. Food Microbiol, 2006, 23(2): 175-183.

[49] EIJSINK V G, SKEIE M, MIDDELHOVEN P H, et al. Comparative studies of class Ⅱa bacteriocins of lactic acid bacteria[J]. Appl Environ Microbiol, 1998, 64(9): 3275-3281.

[50] LÜDERS T, BIRKEMO G A, FIMLAND G, et al. Strong synergy between a eukaryotic antimicrobial peptide and bacteriocins from lactic acid bacteria[J]. Appl Environ Microbiol, 2003, 69(3): 1797-1799.

[51] CINTAS L M, CASAUS P, FERNANDEZ M F, et al. Comparative antimicrobial activity of enterocin L50, pediocin PA-1, nisin A and lactocin S against spoilage and foodborne pathogenic bacteria[J]. Food Microbiology, 1998, 15(3): 289-298.

[52] SVETOCH E A, ERUSLANOV B V, KOVALEV Y N, et al. Antimicrobial activities of Bacteriocins E 50-52 and B 602 against antibiotic-resistant strains involved in nosocomial infections[J]. Probiotics and Antimicrobial Proteins, 2009, 1(2): 136-142.

[53] CHIKINDAS M L, GARCÍA-GARCERÁ M J, DRIESSEN A J, et al. Pediocin PA-1, a bacteriocin from Pediococcus acidilactici PAC1.0, forms hydrophilic pores in the cytoplasmic membrane of target cells[J]. Appl Environ Microbiol, 1993, 59(11): 3577-3584.

[54] MINAHK C J, FARÍAS M E, SESMA F, et al. Effect of enterocin CRL35 on Listeria monocytogenes cell membrane[J]. FEMS Microbiol Lett, 2000,192(1): 79-83.

[55] INGHAM A, FORD M, MOORE R J, et al. The bacteriocin piscicolin 126 retains antilisterial activity in vivo[J]. J Antimicrob Chemother, 2003, 51(6): 1365-1371.

[56] NAGHMOUCHI K, DRIDER D, FLISS I. Action of divergicin M35, a class Ⅱa bacteriocin, on liposomes and Listeria[J]. J Appl Microbiol, 2007, 102(6): 1508-1517.

[57] SUZUKI M, YAMAMOTO T, KAWAI Y, et al. Mode of action of piscicocin CS526 produced by Carnobacterium piscicola CS526[J]. J Appl Microbiol, 2005, 98(5): 1146-1151.