植物内生菌中抗耐药微生物活性成分的研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2020-1471

摘要/Abstract

摘要：

随着抗生素不合理应用所引发的细菌耐药性逐年增多,细菌耐药已经成为全世界都面临的严重问题。面对日益严峻的细菌耐药性问题,除了合理规范的使用抗生素,寻找新的抗微生物药物无疑是解决该问题的重要举措。植物内生菌作为一种新型亟待开发的微生物资源,其丰富的微生物和次级代谢产物多样性为寻找新型抗耐药微生物活性物质提供了可能,显示出极具潜力的研究开发价值。就近年来植物内生菌中抗耐药微生物活性成分的研究进展进行综述,以期为新型抗耐药微生物药物的研究提供参考。

关键词: 植物内生菌, 次级代谢产物, 耐药机制, 抗耐药微生物活性化合物

Abstract:

With the increase of bacterial resistance caused by irrational use of antibiotics year by year,bacterial resistance has become a serious problem all over the world. In order to solve this increasingly serious problem,searching new antimicrobial drugs is undoubtedly an important measure of solving this problem,in addition to the reasonable and standardized application of antibiotics. Plant endophytes are a new type of microbial resource that urgently needs to be developed,and its rich diversity of microbial classification and secondary metabolites provide the possibility of finding new active compounds against drug-resistant microorganism,showing great potential for research and development. In this paper,the recent research progress on active compounds against drug-resistant microorganism in endophytes is reviewed,aiming to provide a reference for the research of new drugs against drug-resistant microorganism.

Key words: plant endophytes, secondary metabolites, drug-resistance mechanism, active compounds against drug-resistant microorganism

王楠, 苏誉, 刘文杰, 封明, 毛瑜, 张新国. 植物内生菌中抗耐药微生物活性成分的研究进展[J]. 生物技术通报, 2021, 37(8): 263-274.

WANG Nan, SU Yu, LIU Wen-jie, FENG Ming, MAO Yu, ZHANG Xin-guo. Research Progress on Active Compounds Against Drug-resistant Microorganism from Plant Endophytes[J]. Biotechnology Bulletin, 2021, 37(8): 263-274.

图/表 1

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植物来源 Plant source	内生菌 Endophytes	化合物 Compounds	抑菌活性 Antibacterial activity	文献 Reference
Kennedia nigriscans	Streptomyces sp. NRRL3052	Munumbicins B	对MRSA菌株有明显的抑制作用,MIC值为2.5 μg/mL	[31]
Kennedia nigricans	Streptomyces sp.NRRL30562	Munumbicins E-4和E-5	对MRSA有明显的抑制作用,MIC值分别为8 μg/mL和 16 μg/mL	[32]
鼠尾草Grevillea pteridifolia	Streptomyces sp.NRRL30566	Kakadumycin A	对VRE以及MRSA均具有强烈的抑制作用,MIC值分别为0.062 μg/mL和 0.5 μg/mL	[33]
纽扣树buttonwood tree	Cytospora sp. CR200	Cytosporone D和E	对MRSA310、屎肠球菌α379、屎肠球菌α436等多株耐药微生物菌株具有中度的体外抗菌活性,MIC值范围是8-64 μg/mL	[34]
红树林植物卤蕨Acrostichum aureurm	Penicillium sp.0935030	环（脯氨酸-苏氨酸）和环（脯氨酸-酪氨酸） Ring（proline-threonine）and ring（proline-tyrosine）	均具有明显抑制MRSA的活性	[35]
Tiliacora triandra	Dothideomycete sp.	Dothideomycetide A	对MRSA菌株显示出抗菌活性,MIC值为256 μg/mL	[37]
红树林植物Pongamia pinnata	Nigrospora sp. MA75	Griseophenone C和Tetrahydrobostrycin	对MRSA均表现出显著的抑制活性,MIC值分别为0.5 μg/mL和2 μg/mL	[38]
海藻Fucus sp.	Streptomyces sp.WR1L1S8	[=2-hydroxy-5-（（6-hydroxy- 4-oxo-4H-pyran-2-yl）methyl）-2- propylchroman-4-one]	对革兰氏阳性致病性MRSA的选择性抑制活性,MIC值为6 μmol/L	[39]
褐藻Rosenvingea sp.	Pestalotia sp.	Pestalone	对MRSA和VRE均显示出有效的抑菌活性,MIC 值分别为37 ng/mL和78 ng/mL	[40]
桂皮Cinnamomum kanehirae	Fusarium oxyporum	Beauvericin和（-）-4,6'-脱水氨基哌啶酮 Beauvericin and（-）-4,6'-anhydrooxysporidinone	对MRSA有抑制活性,MIC值分别为3.125 μg/mL和 100 μg/mL	[41]
红树林植物Rhizophora apiculataz	Phomopsis sp.PSU-MA214	Phomopsanthraquinone	对金黄色葡萄球菌及MRSA良好的抑菌活性,MIC值为128 μg/mL和64 μg/mL	[42]
水稻Oryza sativa L.	Streptomyces sp. BCC72023	Efomycin M、efomycin G和oxohygrolidin	对K-1多药耐药菌株 Plasmodium falciparum良好的抑制活性（IC₅₀值在1.40-5.23 μg/mL范围内）,且化合物efomycin G2对普通蜡状芽孢杆菌也具有较强的抗菌活性,MIC值为3.13 μg/mL	[43]
Daphnopsis americana	内生真菌CR115 Endophytic fungi CR115	Guanacastepene A	对耐药菌株MRSA和VRE显示出良好的抑制作用	[44]
海洋红藻物种Laurencia	Penicillium chrysogenum QEN-24S	Conidiogenone B	对MRSA具有显著的抗菌活性,MIC值为8 μg/mL	[45]
苔藓Everniastrum sp.	内生真菌Ulocladium sp. Endophytic fungi Ulocladium sp.	Ophiobolin P和Ophiobolin T	均对MRSA具有中等的抗菌活性,MIC值分别为31.3 μg/mL和15.6 μg/mL	[46]
红树林 Kandelia candel	Streptomyces sp. HKI0595	Xiamycin	对MRSA菌株和VRE菌株具有良好抑制作用,抑制范围分别为14 mm和12 mm	[47]
头花蓼Polygonum capitatum Buch.-Ham. ex D. Don	Alternaria tenuissima sp. PC-005	5-甲氧基格链孢酚 Ahernariol 5-O-methyl ether	该化合物对肺炎克雷伯杆菌、普通变形杆菌、表皮葡萄球菌、大肠埃希菌、金黄色葡萄球菌、奇异变形杆菌、屎肠球菌等7种耐药微生物均具有良好的抑菌活性,MIC值分别为125、250、125、250、250、125和500 μg/mL	[48]
头花蓼Polygonum capitatum Buch.-Ham. ex D. Don	Gibberella intermedia	镰刀菌酸 Fusaric acid	对多重耐药大肠埃希菌、金黄色葡萄球菌和奇异变形杆菌具有抑制作用,MIC值分别为31.3、125、62.5 mg/mL	[49]
红树林Mangrove	Xylaria cubensis PSU-MA34	Xylacinicacids A and B、2-hexylidene-3-methyl succinic acid 4-methylester、cytochalasin D以及2-chloro-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione等	均对金黄色葡萄球菌ATCC 25923和MRSA有抑制作用,其中化合物2-chloro-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione对金黄色葡萄球菌和MRSA菌株的MIC值为128 μg/ mL	[50]
Garcinia mangostana	Matryephaeria mamane PSU-M76	Botryomaman,2,4-二甲氧基-6-戊基苯酚、（R）-（-）-mellein、primin、顺式4-羟基海藻油、反式-4-羟基海藻油和4,5二羟基-2-己烯酸 Botryomaman,2,4-dimethoxy-6-pentylphenol,（R）-（-）-mellein,primin,cis-4-hydroxymellein,trans-4-hydroxymellein and 4,5-dihydroxy-2-hexenoic acid	所有化合物对MRSA菌株SK1均有抗菌活性。其中化合物 Primin表现出最佳抑制活性,MIC值为8 μg/mL	[51]
柽柳Tamarix	Streptomyces CLR304	304A（维吉尼霉素M1）	对MRSE、MRSA、VISA、VRE有一定抗菌活性,MIC值均在1-4 μg/mL范围内	[52]
Vochysia divergens	Aeromicrobium ponti LGMB491	1-acetyl-β-carboline、indole-3-carbaldehyde、3-（hydroxyacetyl）-indole、brevianamide F、cyclo-（L-Pro-L-Phe）	对MSSA和MRSA均显示中等抑制活性	[53]
药用植物Malay peninsula	内生链霉菌Streptomyces SUK 25	cyclo-（L-Val-L-Pro）、cyclo-（L-Leu-L-Pro）、cyclo-（L-Phe-L-Pro）、cyclo-（L-Val-L-Phe）和N-（7-hydroxy-6-methyl-octyl）-acetamide	对MRSA菌株ATCC 43300有良好的抑制活性,其中cyclo-（L-Leu-L-Pro）对VRE菌株,具有抑制作用,MIC值为12.5 μg/mL	[54]
决明子Cinnamomum cassia Prels	S. cavourensis YBQ59	1-monolinolein、bafilomycin D、nonactic acid、daidzein、3’-hydroxydaidzein	对MRSA和MRSE均显示出抗菌活性,1-monolinolein表现出最强的作用,最低抑菌浓度分别为8.5和14.6 μg/mL	[55]

植物来源 Plant source	内生菌 Endophytes	化合物 Compounds	抑菌活性 Antibacterial activity	文献 Reference
Kennedia nigriscans	Streptomyces sp. NRRL3052	Munumbicins B	对MRSA菌株有明显的抑制作用,MIC值为2.5 μg/mL	[31]
Kennedia nigricans	Streptomyces sp.NRRL30562	Munumbicins E-4和E-5	对MRSA有明显的抑制作用,MIC值分别为8 μg/mL和 16 μg/mL	[32]
鼠尾草Grevillea pteridifolia	Streptomyces sp.NRRL30566	Kakadumycin A	对VRE以及MRSA均具有强烈的抑制作用,MIC值分别为0.062 μg/mL和 0.5 μg/mL	[33]
纽扣树buttonwood tree	Cytospora sp. CR200	Cytosporone D和E	对MRSA310、屎肠球菌α379、屎肠球菌α436等多株耐药微生物菌株具有中度的体外抗菌活性,MIC值范围是8-64 μg/mL	[34]
红树林植物卤蕨Acrostichum aureurm	Penicillium sp.0935030	环（脯氨酸-苏氨酸）和环（脯氨酸-酪氨酸） Ring（proline-threonine）and ring（proline-tyrosine）	均具有明显抑制MRSA的活性	[35]
Tiliacora triandra	Dothideomycete sp.	Dothideomycetide A	对MRSA菌株显示出抗菌活性,MIC值为256 μg/mL	[37]
红树林植物Pongamia pinnata	Nigrospora sp. MA75	Griseophenone C和Tetrahydrobostrycin	对MRSA均表现出显著的抑制活性,MIC值分别为0.5 μg/mL和2 μg/mL	[38]
海藻Fucus sp.	Streptomyces sp.WR1L1S8	[=2-hydroxy-5-（（6-hydroxy- 4-oxo-4H-pyran-2-yl）methyl）-2- propylchroman-4-one]	对革兰氏阳性致病性MRSA的选择性抑制活性,MIC值为6 μmol/L	[39]
褐藻Rosenvingea sp.	Pestalotia sp.	Pestalone	对MRSA和VRE均显示出有效的抑菌活性,MIC 值分别为37 ng/mL和78 ng/mL	[40]
桂皮Cinnamomum kanehirae	Fusarium oxyporum	Beauvericin和（-）-4,6'-脱水氨基哌啶酮 Beauvericin and（-）-4,6'-anhydrooxysporidinone	对MRSA有抑制活性,MIC值分别为3.125 μg/mL和 100 μg/mL	[41]
红树林植物Rhizophora apiculataz	Phomopsis sp.PSU-MA214	Phomopsanthraquinone	对金黄色葡萄球菌及MRSA良好的抑菌活性,MIC值为128 μg/mL和64 μg/mL	[42]
水稻Oryza sativa L.	Streptomyces sp. BCC72023	Efomycin M、efomycin G和oxohygrolidin	对K-1多药耐药菌株 Plasmodium falciparum良好的抑制活性（IC₅₀值在1.40-5.23 μg/mL范围内）,且化合物efomycin G2对普通蜡状芽孢杆菌也具有较强的抗菌活性,MIC值为3.13 μg/mL	[43]
Daphnopsis americana	内生真菌CR115 Endophytic fungi CR115	Guanacastepene A	对耐药菌株MRSA和VRE显示出良好的抑制作用	[44]
海洋红藻物种Laurencia	Penicillium chrysogenum QEN-24S	Conidiogenone B	对MRSA具有显著的抗菌活性,MIC值为8 μg/mL	[45]
苔藓Everniastrum sp.	内生真菌Ulocladium sp. Endophytic fungi Ulocladium sp.	Ophiobolin P和Ophiobolin T	均对MRSA具有中等的抗菌活性,MIC值分别为31.3 μg/mL和15.6 μg/mL	[46]
红树林 Kandelia candel	Streptomyces sp. HKI0595	Xiamycin	对MRSA菌株和VRE菌株具有良好抑制作用,抑制范围分别为14 mm和12 mm	[47]
头花蓼Polygonum capitatum Buch.-Ham. ex D. Don	Alternaria tenuissima sp. PC-005	5-甲氧基格链孢酚 Ahernariol 5-O-methyl ether	该化合物对肺炎克雷伯杆菌、普通变形杆菌、表皮葡萄球菌、大肠埃希菌、金黄色葡萄球菌、奇异变形杆菌、屎肠球菌等7种耐药微生物均具有良好的抑菌活性,MIC值分别为125、250、125、250、250、125和500 μg/mL	[48]
头花蓼Polygonum capitatum Buch.-Ham. ex D. Don	Gibberella intermedia	镰刀菌酸 Fusaric acid	对多重耐药大肠埃希菌、金黄色葡萄球菌和奇异变形杆菌具有抑制作用,MIC值分别为31.3、125、62.5 mg/mL	[49]
红树林Mangrove	Xylaria cubensis PSU-MA34	Xylacinicacids A and B、2-hexylidene-3-methyl succinic acid 4-methylester、cytochalasin D以及2-chloro-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione等	均对金黄色葡萄球菌ATCC 25923和MRSA有抑制作用,其中化合物2-chloro-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione对金黄色葡萄球菌和MRSA菌株的MIC值为128 μg/ mL	[50]
Garcinia mangostana	Matryephaeria mamane PSU-M76	Botryomaman,2,4-二甲氧基-6-戊基苯酚、（R）-（-）-mellein、primin、顺式4-羟基海藻油、反式-4-羟基海藻油和4,5二羟基-2-己烯酸 Botryomaman,2,4-dimethoxy-6-pentylphenol,（R）-（-）-mellein,primin,cis-4-hydroxymellein,trans-4-hydroxymellein and 4,5-dihydroxy-2-hexenoic acid	所有化合物对MRSA菌株SK1均有抗菌活性。其中化合物 Primin表现出最佳抑制活性,MIC值为8 μg/mL	[51]
柽柳Tamarix	Streptomyces CLR304	304A（维吉尼霉素M1）	对MRSE、MRSA、VISA、VRE有一定抗菌活性,MIC值均在1-4 μg/mL范围内	[52]
Vochysia divergens	Aeromicrobium ponti LGMB491	1-acetyl-β-carboline、indole-3-carbaldehyde、3-（hydroxyacetyl）-indole、brevianamide F、cyclo-（L-Pro-L-Phe）	对MSSA和MRSA均显示中等抑制活性	[53]
药用植物Malay peninsula	内生链霉菌Streptomyces SUK 25	cyclo-（L-Val-L-Pro）、cyclo-（L-Leu-L-Pro）、cyclo-（L-Phe-L-Pro）、cyclo-（L-Val-L-Phe）和N-（7-hydroxy-6-methyl-octyl）-acetamide	对MRSA菌株ATCC 43300有良好的抑制活性,其中cyclo-（L-Leu-L-Pro）对VRE菌株,具有抑制作用,MIC值为12.5 μg/mL	[54]
决明子Cinnamomum cassia Prels	S. cavourensis YBQ59	1-monolinolein、bafilomycin D、nonactic acid、daidzein、3’-hydroxydaidzein	对MRSA和MRSE均显示出抗菌活性,1-monolinolein表现出最强的作用,最低抑菌浓度分别为8.5和14.6 μg/mL	[55]