细菌耐药专刊序言

抗生素是人类对抗病原微生物感染的重要"武器"。然而,抗生素的大规模使用导致细菌耐药性不断增强并广泛传播。细菌耐药不仅是医学问题,同时也是社会和经济问题,涉及公共卫生、环境污染、食品安全等诸多领域。本专刊从临床耐药与流行病学、动物及环境耐药、细菌耐药机制、抗菌药物研发和耐药防控策略等角度对细菌耐药性问题进行了较系统的综述和探讨,为全面认识细菌耐药现状、深入开展耐药机制研究并制定综合防控策略等提供参考。     

大熊猫源细菌耐药性研究进展

耐药菌和耐药基因已成为一种新型环境污染物,引发世界公共卫生问题。细菌耐药性尤其是多重耐药菌在人医临床、畜禽养殖以及环境传播等多个方面得到越来越多的关注,而关于大熊猫等野生动物的耐药性研究相对较少。大熊猫(Ailuropoda melanoleuca)是世界公认的珍稀野生动物,其种群数量易受到各种疾病的威胁,尤其是肠道细菌性疾病。随着抗菌药物在疾病预防和控制中的普遍使用,由此带来的耐药性危害日益明显。本文总结了关于大熊猫源细菌耐药的国内外研究报道,对其耐药表型、耐药基因型、耐药机制及水平传播机制等方面内容进行了综述,旨在为大熊猫源细菌耐药性的研究和防控提供依据,为临床科学用药提供理论参考,从而助力大熊猫迁地保护。     

细菌生物膜与耐药性相关性研究进展

细菌生物膜是一种包裹于细胞外多聚物基质中不可逆的黏附于非生物或生物表面的微生物细胞菌落.生物膜状态下的细菌相对其浮游状态具有显著增强的耐药性,对人及动物细菌性感染具有重要研究价值.然而尽管动物细菌耐药性被广泛报道,却很少涉及细菌生物膜与其之间的相关性,本文综述了细菌生物膜的耐药机制并探讨了细菌生物膜与动物源性细菌耐药性的关系,可作为研究细菌耐药性及控制动物产品安全的参考.     

耐药细菌中交互敏感现象研究进展

细菌耐药性是全球亟待解决的重要公共卫生问题之一,耐药病原菌对人类和动物健康构成极大威胁。交互敏感性、附带敏感性(collateral sensitivity)是指耐药细菌在进化过程中出现的对一类抗菌药物耐药,而对另一类或几类抗菌药物更加敏感的现象。利用交互敏感策略限制甚至逆转细菌耐药性以恢复其对抗菌药物的敏感性是细菌耐药性研究的热点。本文综述了细菌交互敏感的最新研究进展,主要从交互敏感性的概念、表型及机制研究等方面进行阐述,以期为防控和治疗耐药病原菌感染提供新思路。     

耐药细菌分析——“只有民族的才是世界的”

正细菌的耐药问题已经成为一种全球性的严重威胁[1],耐甲氧西林金黄色葡萄球菌(MRSA)、多重耐药鲍曼不动杆菌和耐药性艰难梭菌等多种耐药细菌感染疾病负担巨大,中国的情况尤其严重。近期中国研究团队在动物和人源细菌中均发现了一种新型的位于细菌质粒上的粘菌素耐药基因mcr-1[2],使细菌耐药问题受到进一步关注。本刊2015年第1期刊登了杨永刚、陈瑜等的研究文章"耐甲氧西林金黄色葡萄球菌分型及流行现状"[3],     

CRISPR-Cas9技术在细菌耐药性防控研究进展

近年来,多种新型耐药基因的出现和全球性流行,严重威胁了全球公众健康。CRISPR-Cas9系统(clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9 system)是细菌的一种适应性免疫系统,可切割耐药基因、抵御外来核酸入侵,现已作为一种新型基因编辑工具应用于防控细菌耐药性研究。本团队已建立了一种单质粒介导靶向mcr-1基因的CRISPR-Cas9系统,能有效并特异性消除黏菌素耐药大肠杆菌中的mcr-1,恢复其对黏菌素的敏感性。同时也发现在临床中应用还需要优化其递送方式。本文对近几年该技术在细菌耐药性防控方面的研究进展进行了综述,包括CRISPR-Cas9系统的发现过程、作用机制、递送方式、在体外检测实验结果的进展以及当前存在的问题等方面,以期为防控细菌耐药性提供新思路。     

合肥地区动物源性大肠埃希菌的血清型分布与耐药性分析

目的了解安徽省合肥地区动物源性大肠埃希菌的血清型分布和耐药状况,以期筛选出菌苗株和指导临床合理用药。方法对46份疑似大肠埃希菌病病料进行细菌分离培养、生化编码鉴定和致病性测定。采用玻片凝集试验对分离到的46株致病性大肠埃希菌进行血清型鉴定。同时分别采用K-B纸片琼脂扩散法和双纸片增效法检测致病性大肠埃希菌的耐药性和ESBLs阳性菌株。结果46株致病性大肠埃希菌中,除7株细菌未能定型外,其余39株细菌分布于10个血清型,O127：K63血清型为优势血清型,占定型菌株的33．33％。46株致病性大肠埃希菌对21种抗菌药物均呈现不同程度的耐药性,15个ESBLs阳性菌株表现为多重耐药,对各种抗菌药物的耐药率均高于ESBLs阴性菌株。结论O127：K63血清型为优势血清型,可作为菌苗株。合肥地区动物源性大肠埃希菌耐药性较为严重,尤其是产ESBLs大肠埃希菌多重耐药更为突出。     

细菌耐药性的起源与演变

细菌的耐药性问题不断加剧,已经引起了全球研究人员的关注。然而,早在使用抗生素之前,细菌的耐药基因的雏形就已经存在于自然环境中并且来源广泛,其耐药性的演变也经历了复杂的过程。本文结合国内外的相关研究,对细菌耐药基因的起源、耐药性的演变及耐药机制等方面进行综述,期望为研究细菌的耐药机理和预测耐药性的演变提供参考。     

细菌耐药影响肠道菌群及其宿主免疫调控

抗生素在养殖业、医疗业及制药业的广泛应用导致环境中的细菌耐药性日益严重,环境中的抗生素及耐药细菌一旦进入人体肠道,将破坏肠道菌群稳态,对人体健康造成威胁,而残存于饮食中的环境污染物则加剧了细菌耐药造成的人体健康影响。文中在总结大量文献的基础上,阐述了细菌耐药对人体和动物肠道菌群的影响机制及其相关的机体免疫调控,以环境中影响人体肠道菌群获得耐药性的来源作为切入点,阐述抗生素和耐药细菌进入人体肠道后对人体肠道菌群结构和耐药基因组成的影响,以及与人体免疫和免疫调节相关疾病之间的相关机制,并对今后的研究方向进行了展望。     

细菌耐药机制及耐药性消除的研究进展

抗菌药物选择压力导致细菌耐药性日趋严重。究其根源,细菌耐药机制的探讨是为了揭示菌株耐药的根本原理,并从中找到消除耐药性的有效方法。本研究就现今国内外对耐药机制的研究以及耐药性消除的研究进行综述。     

害虫抗药性的显性水平与抗性进化

对杀虫剂的代谢抗性和主要靶标抗性的显性水平作了理论解释,其中包括昆虫对Bt抗性的显性水平的解释。并对抗性显性具有的多变性作了阐述。分析抗性显性水平与抗药性进化的关系,认为在抗性进化早期抗性表现为显性的基因频率上升快于抗性表现为隐性时;但在抗性等位基因频率较高且出现抗性纯合子个体时,抗性表现为隐性的基因频率上升显著快于抗性表现为显性时。最后论述抗性显性在抗性治理中的应用。     

甜菜夜蛾的抗性及抗性机理研究进展

甜菜夜蛾Spodoptera exigua(Hübner)是世界性农业害虫,近年来在我国由次要害虫上升为主要害虫。甜菜夜蛾对很多种化学杀虫剂和生物杀虫剂产生了抗性。本文分别阐述了甜菜夜蛾对常用杀虫剂如有机磷类、拟除虫菊酯类、氨基甲酸酯类、生长调节类杀虫剂、Bt杀虫剂等的抗性发展现状,并且对抗药性机理进行了总结,提出了抗性治理措施。     

Herbicide resistance—what have we learned from other disciplines?

Herbicide resistance is a growing threat to agriculture and has parallels to resistances to fungicides and insecticides. However, there are many reasons to treat the resistance to herbicides differently. To highlight these similarities and differences, three pests, a weed, an insect, and a disease that have shown the ability to rapidly develop resistance to a variety of products and product classes were used as illustrations. The situation in herbicide resistance is approaching a point already experienced by the other pest control disciplines, and thus, it is worthwhile to revisit their experiences.     

我国麦蚜抗药性及研究现状

麦蚜是危害我国小麦Triticum aestivum L.生产的主要害虫,具有分布广、数量大、繁殖力强以及远距离迁飞等特点,不仅直接吸食小麦汁液,还传播多种植物病毒,每年造成小麦减产10%~30%。目前对麦蚜的防控主要以化学防治为主,但由于化学杀虫剂长期或不合理的使用,多地麦蚜对常用杀虫剂产生了不同程度的抗性。本文从麦蚜抗药性测定方法、抗性水平及交互抗性、代谢和靶标抗性机制、以及麦蚜抗药性综合治理等方面进行了综述,以期为麦蚜的防治及杀虫剂的持续合理使用提供理论参考和依据。     

褐飞虱抗药性研究现状

褐飞虱Nilaparvata lugens(Stal)对杀虫剂产生抗药性是其近年来暴发频繁的重要原因。文章综述国内外关于褐飞虱抗药性的研究成果,包括褐飞虱抗性测定方法、抗药性的发展、交互抗性、抗性遗传、抗性机理及抗性治理等。田间褐飞虱种群对新烟碱类药剂产生不同程度的抗药性,其中对吡虫啉产生高水平到极高水平抗性,对氯噻啉和噻虫嗪分别产生中等水平和低水平的抗药性,对呋虫胺和烯啶虫胺仍然处于敏感性阶段。此外,褐飞虱种群对噻嗪酮(昆虫生长调节剂)产生低水平到中等水平抗性。长期大面积使用化学药剂是褐飞虱产生抗药性的重要原因。因此,必须加强褐飞虱的抗性治理,以延缓其抗药性进一步发展。     

害虫及害螨对阿维菌素抗药性研究进展

阿维菌素(avermectins)是一类新型高效广谱的生物源农药,对多种害虫及害螨具有极好的防效。随着阿维菌素在害虫及害螨防治中的广泛应用,害虫和害螨对其的抗性问题日益受到关注。文章综述国内外的最新研究结果表明:小菜蛾Pluttella xylostella(L.)、二斑叶螨Tetranychus urticate Koch等已对阿维菌素产生抗性,对阿维菌素产生抗性的害虫和螨并不总是表现适合度劣势,且抗性一旦产生敏感性较难以恢复;抗性遗传多数由多基因、不完全隐性控制;抗性机理涉及多种因素。综合分析发现害虫和螨对阿维菌素存在较大的、潜在抗性风险。     

西花蓟马的抗药性及其治理策略

西花蓟马Frankliniella occidentalis（Pergande）是世界性的园艺作物上的重要害虫,几乎对每种类型的杀虫剂均产生了抗药性,包括有机磷、氨基甲酸酯、拟除虫菊酯类杀虫剂和多杀菌素等。本文对国外西花蓟马的抗药性发展现状和抗性机制进行了总结,并提出了抗性治理策略,即科学合理使用杀虫剂,结合栽培防治、物理防治、生物防治和寄主植物抗性等方式降低杀虫剂对西花蓟马的选择压,从而达到抗性治理的目的。     

Biochemistry and genetics of insect resistance to Bacillus thuringiensis insecticidal crystal proteins

Abstract Current knowledge of biochemical mechanisms of insect resistance to Bacillus thuringiensis is reviewed. Available information on resistance inheritance and on patterns of cross-resistance is included. Modification of the binding sites for B. thuringiensis insecticidal crystal proteins has been found in different populations of three insect species. This resistance mechanism seems to be inherited as a single recessive or partially recessive major gene, and the resistance levels reached are high. Altered proteolytic processing of B. thuringiensis crystal proteins has been suggested to be involved in one case of resistance. From the available data it seems that binding site modification is the most significant resistance mechanism under field conditions.     

Plant Innate Immune Response: Qualitative and Quantitative Resistance

Plant diseases, caused by microbes, threaten world food, feed, and bioproduct security. Plant resistance has not been effectively deployed to improve resistance in plants for lack of understanding of biochemical mechanisms and genetic bedrock of resistance. With the advent of genome sequencing, the forward and reverse genetic approaches have enabled deciphering the riddle of resistance. Invading pathogens produce elicitors and effectors that are recognized by the host membrane-localized receptors, which in turn induce a cascade of downstream regulatory and resistance metabolite and protein biosynthetic genes (R) to produce resistance metabolites and proteins, which reduce pathogen advancement through their antimicrobial and cell wall enforcement properties. The resistance in plants to pathogen attack is expressed as reduced susceptibility, ranging from high susceptibility to hypersensitive response, the shades of gray. The hypersensitive response or cell death is considered as qualitative resistance, while the remainder of the reduced susceptibility is considered as quantitative resistance. The resistance is due to additive effects of several resistance metabolites and proteins, which are produced through a network of several hierarchies of plant R genes. Plants recognize the pathogen elicitors or receptors and then induce downstream genes to eventually produce resistance metabolites and proteins that suppress the pathogen advancement in plant. These resistance genes (R), against qualitative and quantitative resistance, can be identified in germplasm collections and replaced in commercial cultivars, if nonfunctional, based on genome editing to improve plant resistance.     

Stability analyses for estimating relative durability of quantitative resistance

Summary Experiments in which a series of host cultivars are inoculated in all combinations with a series of pathogen isolates have been used to detect specificity in the host resistance. A theoretical model of polygenic resistance involving both general and specific interactions with pathogen virulence was developed to test the abilities of statistical analyses to discriminate between host genotypes with different levels of general and specific resistance. Estimates of levels of specific resistance could be obtained in regressions of disease severity scores for each host cultivar X pathogen isolate combination vs. the virulence index of each isolate. If the virulence index was based on the mean disease severity induced by the isolate over all host cultivars, the slopes of the regression lines were correlated with the levels of specific resistance in host cultivars. If the virulence index was based on the disease severity induced by the isolate on a host cultivar with a minimum of specific resistance, the mean squares for deviations from the regression were correlated with the levels of specific resistance in host cultivars. A method was developed to consistently choose host cultivars with minimum specific resistance. The two regression analyses gave estimates of specificity in randomly generated, model genotypes of approximately equal accuracy, although the second method appeared to be more accurate when the numbers of loci controlling resistance and virulence were small. The best estimates of numbers of genes for specific resistance were obtained by calculating a rating based on mean disease severity, the mean square for deviation from the regression on the virulence index based on disease severity on the cultivar with minimum specific resistance and the slope of the regression on the virulence index based on the mean disease severity. The best estimates of proportions of resistance genes that were specific were obtained by calculating a rating based on the above deviation mean square and slope alone.Cooperative investigation of the U.S. Department of Agriculture, Agricultural Research Service and the North Carolina Agricultural Research Service. Journal Series Paper No. 8326 of the North Carolina Agricultural Research Service