细菌持留与抗生素表型耐药机制

持留菌是细菌群体中一小部分具有表型耐药的细菌。自1944年被发现后,近几十年来因其在慢性持续性感染和生物膜感染中的重要作用而得到越来越多的重视。已有的研究结果表明,细菌持留的机理复杂,涉及的相关信号通路有毒素-抗毒素系统、细胞能量代谢及蛋白核酸合成等生理状态的降低、DNA保护修复系统、蛋白酶系统、反式翻译、外排泵系统等。虽然不同细菌的持留机理有一定的相似性和保守性,但不同细菌的持留机制也存在差异,如毒素-抗毒素系统在大肠埃希菌(Escherichia coli)中的过度激活可导致持留菌增加,但在金黄色葡萄球菌(Staphylococcus aureus)中却并无相同作用。本文从持留菌的研究历史出发,综述了当前对革兰氏阴性菌和阳性菌的持留机制方面的研究进展,同时探讨了在持留菌相关感染疾病方面的治疗策略,以期为更好地解决持留菌带来的问题,缩短治疗时间提供新的思路。     

金黄色葡萄球菌sdhCAB操纵子影响持留菌形成机制的研究

持留菌是细菌群体中的一小部分细菌,可耐受致死浓度抗生素的处理,是引起慢性感染的重要原因。金黄色葡萄球菌(Staphylococcus aureus,S. aureus)作为常见致病菌,有重要临床意义。分别敲除sdhA和sdhB后,金黄色葡萄球菌持留菌形成水平下降,但sdhCAB操纵子对持留菌形成的作用及机制尚不明确。本研究敲除sdh操纵子,通过酸压力、氧化压力、热压力及抗生素压力实验检测敲除株的持留菌水平,转录组测序检测敲除株的代谢通路变化,高通量微生物细胞表型检测评估敲除株的代谢水平变化。结果显示,敲除sdhCAB或sdhAB后,金黄色葡萄球菌对酸压力、氧化压力的耐受能力均下降;而在抗生素压力、热压力条件下,分别仅sdhCAB敲除株、sdhAB敲除株耐受能力下降。转录组测序发现,sdhCAB敲除后三羧酸循环、甲烷代谢通路及聚合酶Ⅳ等基因表达上调,耐药相关基因、氨基酸代谢基因、糖类代谢基因、卟啉代谢基因及一些转运体基因等表达下调,提示这些通路的基因参与sdhCAB影响持留菌形成的过程。此外,高通量微生物细胞表型检测发现,敲除sdhCAB可降低金黄色葡萄球菌对琥珀酸、柠檬酸、糖原、L-天冬氨酸等64种碳源的代谢。结果提示,sdhCAB操纵子对金黄色葡萄球菌持留菌形成水平有重要影响。本研究初步阐明了sdhCAB操纵子影响持留菌形成的可能机制,为研究和治疗金黄色葡萄球菌慢性感染提供了新的思路。     

耐甲氧西林金黄色葡萄球菌的耐药及其检测方法

耐甲氧西林金黄色葡萄球菌（MRSA）是引起医院感染的多重耐药菌,其有效的治疗药物为万古霉素。近年已发现对万古霉素耐受的金黄色葡萄球菌,金黄色葡萄球菌一旦对万古霉素耐药,临床将面临无药可供选择的局面。由于其所造成治疗上的困难,对其耐药机制的深入研究和该菌准确、及时的检出对于寻找新的治疗靶位和防止其播散有着极其重要的意义。本文就mecA耐药决定子、调节基因、染色体上的辅助基因对耐甲氧西林金黄色葡萄球菌耐药表达的影响及其表型和基因检测方法作一综述。     

金黄色葡萄球菌耐药基因及新型抗菌药物的研究进展

金黄色葡萄球菌(Staphylococcus aureus,S.aureus),简称金葡菌,是一种临床常见致病菌,可引起皮肤化脓性感染、肺炎、心包炎、败血症及脓毒血症等多种疾病。目前临床上金黄色葡萄球菌的多重耐药情况已十分严峻,特别是耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)的出现,已成为临床抗感染治疗的棘手难题,严重危害人类健康。本文主要介绍金黄色葡萄球菌基因水平的耐药性、新型抗菌药物的研发及临床治疗金黄色葡萄球菌感染三方面的进展,为金黄色葡萄球菌的耐药性研究及耐药菌株的临床有效治疗提供科学依据。     

鲍曼不动杆菌AmpC酶的检测

<正>鲍曼不动杆菌是医院感染重要条件致病菌。近年来,鲍曼不动杆菌感染日益增多,仅次于金黄色葡萄球菌和大肠埃希菌,并且呈现多重耐药现象,已引起临床医生和微生物工作者的高度关注,而其体内产生的AmpC酶是导致鲍曼不动杆菌耐药的重要原因之一。     

耐药机制指导下的抗金葡菌药物开发现状

金黄色葡萄球菌是全球院内感染的首要病原菌,临床分离的金葡菌80%以上为耐甲氧西林(MRSA)菌株,因其耐药性,尤其是多重耐药性的快速增长,抗MRSA感染日益成为抗感染治疗的难点和热点。近年来,人们在充分认识金葡菌耐药机制的基础上,积极开发新型抗MRSA药物,取得了长足发展。对MRSA的耐药机制及该机制指导下抗金葡菌药物开发现状作一综述。     

金黄色葡萄球菌溶血素的研究进展

金黄色葡萄球菌简称金葡菌,是一类革兰阳性需氧或兼性厌氧菌,可导致化脓性感染、肺炎、伪膜性肠炎、心包炎等局部感染,以及败血症、脓毒血症等全身感染。金黄色葡萄球菌的致病力强弱主要取决其产生的毒素和侵袭性酶,其中溶血素已经成为该细菌的一个重要致病因子。本文对金黄色葡萄球菌溶血素的分子特征、作用机制、免疫预防及临床应用方面的研究进展进行综述。     

医院感染病原菌及耐药性监测报告

从３９０４ 例住院病人标本中分离出医院内感染病原菌７８１ 株,结合临床常用的１４ 种抗菌药物药敏试验结果进行整理分析。结果,革兰阳性球菌所占比例呈上升趋势,革兰阴性杆菌呈下降趋势。引起医院感染的主要病原菌为真菌、大肠埃希菌、克雷伯菌、肠球菌、金黄色葡萄球菌。２ 年间金黄色葡萄球菌对青霉素的耐药率已＞ ９３ ％ ,对第三代喹诺酮类的耐药率下降了１６．６６ ％ ～４０．８３ ％ 。肠球菌对万古霉素的耐药率上升了２７．５９ ％ 。克雷伯菌、沙雷菌、大肠埃希菌对头孢菌素类、第三代喹诺酮类的耐药率呈上升趋势。金黄色葡萄球菌、表皮葡萄球菌、肠杆菌属、铜绿假单胞菌对阿米卡星的耐药率呈下降趋势。     

耐万古霉素的金黄色葡萄球菌

目前认为万古霉素中度耐药的金黄色葡萄球菌菌株一般从苯唑西林耐药的金黄色葡萄球菌转变而来。万古霉素中度耐药的金黄色葡萄球菌感染患者往往长期使用万古霉素或有慢性疾病。目前还没有系统检测万古霉素中度耐药的金黄色葡萄球菌的试验。如果用万古霉素治疗苯唑西林耐药的金黄色葡萄球菌感染失败,临床医生应警觉是否为万古霉素中度耐药的金黄色葡萄球菌感染。     

儿科住院患儿下呼吸道感染的病原菌分布及耐药性分析

目的:分析我院儿科患儿医院下呼吸道感染的病原菌分布情况和耐药性情况,为临床合理使用抗菌药物提供依据。方法:本文以我院儿科近年来(2015年8月至2016年8月期间)临床收治的下呼吸道感染患儿566例为研究对象,针对患儿的病原菌分布情况和耐药性情况进行了调查研究。结果:本次研究的566例患儿共检出病原菌126株,病原菌检出率为22.26%。其中肺炎克雷伯菌、大肠埃希氏菌、金黄色葡萄球菌和表皮葡萄球菌,构成比分别为23.80%、17.56%、10.32%和7.14%;肺炎克雷伯菌对氨苄西林、头抱曲松、复方新诺明、氨曲南的耐药率分别为76.67%、73.33%、36.67%和26.67%;大肠埃希氏菌对氨苄西林、复方新诺明、头抱曲松、哌拉西林、头孢吡肟、头孢他啶的耐药率分别为72.73%、72.73%、68.18%、45.46%、27.27%、22.72%;金黄色葡萄球菌对氨苄西林、红霉素、阿奇霉素、克林霉素、复方新诺明、庆大霉素的耐药率分别为100.00%、84.6%、84.6%、69.23%、53.85%和38.46%。结论:儿科医院呼吸道感染的病原菌以肺炎克雷伯菌、大肠埃希氏菌和金黄色葡萄球菌为主,且多重耐药菌感染增多,临床抗菌药选择的应根据药敏试验结果进行针对性的选择用药以提高临床治疗的有效性及合理性,减少耐药菌株产生。     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.     

Composition and diversity of bird communities in Swedish farmland–forest mosaic landscapes

CapsuleThe amount of forest (at local and landscape scales) and occurrence of residual habitats at the local scale are shown to be the major factors influencing bird community composition in farmland–forest landscapes in central Sweden.

Aims To investigate the importance of local habitat and landscape structure for breeding birds in farmland–forest landscapes in central Sweden.

Methods Breeding birds were censused at 292 points. A detailed habitat mapping was made within 300 m of the points. Within a 300–600 m radius only two major habitats (forests and arable fields) were identified.

Results Cluster analyses of bird communities identified three site types that also differed in habitat composition: (i) partially forested sites in forested landscapes; (ii) heterogeneous sites with residual habitats in mosaic landscapes; and (iii) field-dominated farmland sites in open landscapes. A total of 19 of 25 farmland bird species (restricted to farmland or using both farmland and forest) had the highest abundance in farmland sites with mosaics of forest and farmland, while only six farmland species had the highest abundance in field-dominated sites. The bird community changed from being dominated by farmland species to being dominated by forest species (common in forest landscapes without farmland) at small proportions (10–20%) of forest at the local scale. A major difference in habitat composition between heterogeneous and field-dominated sites was the occurrence of different residual habitats (e.g. shrubby areas and seminatural grasslands). These habitats seemed to influence bird community composition more than land-use, despite covering <10% of the area. Seminatural grasslands were important for bird community composition and species-richness, but grazing seemed to be less important. Among different land-use types, cereal crops were the least preferred fields. Set-asides with tall vegetation and short rotation coppices were positively associated with species-richness of farmland birds.

Conclusion In general, the composition of the landscape was important for bird community composition, although amount and distribution of forests, occurrence of residual habitats and land-use of fields at the local scale had the strongest influence on bird community composition. The possible implications of these patterns for managing farmland–forest landscapes are discussed.     

Chemical constituents from the fruits of Rhus typhina L. and their chemotaxonomic significance

This work describes the isolation and characterization of twenty-nine compounds from the fruits of Rhus typhina L., including eleven flavonoids (1–11), eleven phenols (12–22), two pentacyclic triterpenes (23–24), two organic acids (25–26), one lumichrome (27), one courmarin (28) and one pyrimidine (29) on the basis of their spectroscopic data. Compounds apigenin (1), daidzein (4), orobol (5), 3′, 5, 5′, 7-tetrahydroxyflavanone (6), naringenin (7), butein (8), (-)-catechin (9), quercetin-3-O-α-L-(3″-O-galloyl)-rhamnoside (11), 2-hydroxybenzoic acid (13), 4-hydroxybenzaldehyde (14), vanillin (15), methyl 3,4-dihydroxybenzoate (16), 3,5-dihydroxybenzamide (18), tyrosol (19), caffeic acid (20), 3-(2,4,6-trihydroxyphenyl)-1-(4-hydroxyphenyl)-propan-1-one (21), phlorizin (22), friedelin (23), oleanolic acid (24), 4,4-dimethyl-heptanedioic acid (25), anthranilic acid (26), lumichrome (27), scoparone (28) and uracil (29) have not been recorded before in this plant. This is the first report on the occurrence of compounds 4–7, 9, 11, 13–14, 16, 18–21, 25–29 from the genus Rhus. Moreover, the chemotaxonomic significance of these isolated compounds was also summarized.