Myxoma virus M128L is expressed as a cell surface CD47-like virulence factor that contributes to the downregulation of macrophage activation in vivo

The M128L myxoma virus gene expresses a five-membrane spanning cell surface protein with significant amino acid homology to the cellular CD47 proteins. CD47, also called integrin-associated protein (IAP), is associated with the modulation of leukocyte adhesion, motility, activation, and phagocytosis. Creation of an M128L-deletion mutant myxoma virus strain and subsequent infection of the European rabbit demonstrated that M128L is necessary for the production of a lethal infection in susceptible rabbits, while it is fully dispensable for virus replication in vitro. Secondary sites of infection developed on the majority of rabbits infected with the M128L-deletion mutant (vMyx128KO), demonstrating that the M128L protein is nonessential for the dissemination of virus within the host. Although the size and severity of the primary lesions on vMyx128KO-infected rabbits were comparable to rabbits infected with the wild-type virus at the early stages of disease progression, by day 7 the reduced virulence of the vMyx128KO virus was clearly evident and all of the animals recovered from infection by the M128L-knockout virus. Histological analysis of the tissues of vMyx128KO-infected rabbits revealed greater activation of monocyte/macrophage cells in infected and/or lymphoid tissues when compared to those of wild-type myxoma-infected rabbits. We conclude that the M128L protein is a novel CD47-like immunomodulatory gene of myxoma virus required for full pathogenesis of the virus in the European rabbit and that its loss from the virus results in increased activation of monocyte/macrophage cells during infection.     

A single amino acid change in the C-terminal domain of the matrix protein M1 of influenza B virus confers mouse adaptation and virulence

Serial passage of an initially avirulent influenza B virus, B/Memphis/12/97, resulted in the selection of a variant which was lethal in mice. Virulence correlated with improved growth in vivo and prolonged replication. Sequencing of the complete coding regions of the parent and mouse-adapted viruses revealed 8 amino acid differences. Sequencing and characterization of intermediate passages suggested that one change in the C-terminal domain of the M1 protein, an asparagine to a serine at position 221, was responsible for acquisition of virulence and lethality. Site-directed mutagenesis of the M segment of a different virus, B/Yamanashi/166/98, to change this amino acid residue confirmed its importance by conferring improved growth and virulence in mice. This observation suggests a role for the C domain of the M1 protein in growth and virulence in a mammalian host.     

Molecular epidemiology of extraintestinal pathogenic (uropathogenic) Escherichia coli

Molecular epidemiological analyses of extraintestinal pathogenic Escherichia coli (ExPEC), which are also called "uropathogenic E. coli" since they are the principle pathogens in urinary tract infection, involve structured observations of E. coli as they occur in the wild. Careful selection of subjects and use of appropriate methods for genotyping and statistical analysis are required for optimal results. Molecular epidemiological studies have helped to clarify the host-pathogen relationships, phylogenetic background, reservoirs, and transmission pathways of ExPEC, to assess potential vaccine candidates, and to delineate areas for further study. Ongoing discovery of new putative virulence factors (VFs), increasing awareness of the importance of VF expression and molecular variants of VFs, and growing appreciation of transmission as an important contributor to ExPEC infections provide abundant stimulus for future molecular epidemiological studies. Published by Elsevier GmbH.     

利福平—珊瑚羟磷灰石复合物预防骨感染的实验研究

目的：本研究旨在探讨珊瑚羟磷灰石（ｃｏｒａｌｉｎｅｈｙｄｒｏｘｙａｐａｔｉｔｅｐｏｒｉｔｅｓ，ＣＨＡＰ）作为抗生素载体及释放系统的特征以及局部释放抗生素防治骨感染的作用。方法：将ＣＨＡＰ作为抗生素的载体，以利福平（ｒｅ－ｆａｍｐｉｃｉｎ，Ｒ）为模型药物，制备成吸附抗生素的ＣＨＡＰ复合物（Ｒ－ＣＨＡＰ），进行体内、外药物释放试验。采用高效液相色谱法测定标本的ＲＦＰ浓度。将Ｒ－ＣＨＡＰ、空白ＣＨＡＰ分别植入污染不同毒力金葡菌的兔骨缺损区，经放射学检查，细菌培养及组织病理学检查判断骨感染的发生情况。结果：体内、外药物释放试验显示，Ｒ－ＣＨＡＰ在４周内持续释放高浓度的抗生素，血清浓度明显低于局部浓度；组织炎性反应小，生物相容性好。Ｒ－ＣＨＡＰ植入污染不同毒力金葡菌的骨缺损区，其抗菌作用效果无差异（Ｐ＞０．０５），较植入空白ＣＨＡＰ对照组的骨感染发病率低（Ｐ＜０．０５）；两者对金葡菌无特异性的亲和力。结论：ＣＨＡＰ是一种较为理想的抗生素载体及释放系统，局部应用Ｒ－ＣＨＡＰ可有效地预防骨缺损深部感染的发生，应进一步探索其应用前景     

携带毒力岛大肠杆菌性小儿腹泻

目的：探讨携带毒力岛大肠杆菌（HPIEC）在小儿腹泻中的病原学地位。方法：采用PCR扩增和菌落原位杂交检测HPIEC－irp2毒力岛基因,并用血清学分型和聚合酶链反应（PCR）法检测各类致泻大肠杆菌。结果：从1032例腹泻患者粪便中分离出652株大肠杆菌,经血清学和PCR毒力基因分型,检出各类致泻大肠杆菌225株,其中肠致病性大肠杆菌（EPEC）20株,ETEC81株,产志贺样毒素大肠杆菌（SLTEC）47株,产志贺样毒素侵袭性大肠杆菌（ESIEC）74株,产毒素大肠杆菌（EIEC）3株。所有致泻大肠杆菌和未能分型的普通大肠杆菌株,再用HPIEC－irp2探针作菌落原位杂交,共检出携带毒力岛大肠杆菌（HPIEC－irp2)112株,总阳性率为17．2％。其中41例是从致泻大肠杆菌ESIEC（24／74）和SLTEC（17／47）中检出。携带毒力岛大肠杆菌性小儿腹泻的主要临床表现为食欲不振（87．5％）,腹痛（58．0％）,腹泻（＞6次／d,75．9）,发热（50．9％）,以粘液便为主（69．6％）。结论：携带毒力岛大肠杆菌是引起小儿腹泻的重要病原菌之一。     

山东省分离的霍乱弧菌毒力基因的研究

目的：了解山东省不同年代、不同地区收集的霍乱菌株携带的毒力基因情况、分布特点和变迁。方法：应用分子杂交、PCR技术对霍乱弧菌的CTX基因元件中的ctxA、zot基因，VPI毒力岛中的tcpA、tcpH、aldA、toxT、acfB基因，TLC因子中的cri、orf2—3基因，RTX基因簇中的rtxA、rtxC，以及toxR基因进行了检测。结果：用原位杂交检测，180株霍乱弧菌中有168株携带CTX遗传单元中的ctxA、zot、RS1基因，阳性率均为93．33％，表现出高度的一致性。用打点杂交检测不同时期的28株01群霍乱弧菌，所有被检菌都具有ToxR、RTX相关基因，在1980～1987年间分离的O1群霍乱弧菌流行株中，有92．86％携带编码TLC因子的基因，而1994～2000年间分离的流行株菌株中编码TLC因子的基因携带率仅有7．14％。Southern杂交结果显示，48株O1群霍乱弧菌可产生大小为9．4kb和6．5kb左右的两条ctxA杂交带，用zot基因探针进行杂交，11株O1群霍乱弧菌可产生与ctxA杂交带同样大小的条带。1株O139霍乱弧菌具有检测的所有毒力基因，但其ctxA（zot）杂交带与O1群霍乱弧菌有差异。结论：目前已知的霍乱弧菌毒力基因在山东省分离到的菌株中有广泛的分布，并且随时间的推移而发生变迁。     

嗜肺军团菌的致病性及其分泌系统

嗜肺军团菌是引起军团菌病的的重要病原体,它可在原虫及人体巨噬细胞内生存及复制,并最终导致宿主细胞死亡.军团菌的致病机制尚不完全明确,目前研究表明,其致病性主要涉及细菌在细胞内的存活及复制、毒力因子的作用及其分泌系统,该文就此作了简要概述.     

幽门螺杆菌毒力因子的研究进展

幽门螺杆菌(HP)是造成上消化道疾病的主要因素。HP能分泌许多致病因子,这些致病因子分为定植因子和毒力因子。HP的各种毒力因子均具有遗传多样性和地区分布的差异,与不同HP相关性疾病之间存在相关性。毒力因子在病变过程中起的作用不尽相同,决定感染后炎症、溃疡及胃癌等临床转归。本文就其研究现状予以综述。     

Alterations of growth,biofilm-forming,and gene expression of Bordetella pertussis by antibiotics at sub-minimum inhibitory concentrations

Bordetella pertussis is the primary agent of the acute respiratory disease pertussis. It has been reported that the disease has recently become more common, especially in adults and adolescents, and adaptation of the pathogen is thought to have an important influence on the recurrence of the disease. This study aims to determine the effect of erythromycin, azithromycin, and trimethoprim-sulfamethoxazole used in the treatment of pertussis on the virulence gene expressions (prn, ptxS1, fhaB), biofilm-forming and growth of B. pertussis. In this study, the minimum inhibitory concentration (MIC) values of azithromycin and erythromycin in B. pertussis local strain Saadet were determined to be 0.09 μg/mL and 0.3 μg/mL, respectively. However, the Tohama-I and Saadet strains were resistant to trimethoprim-sulfamethoxazole (MIC>32 μg/mL). The biofilm-forming of the Saadet strain decreased with the increase in antibiotic doses. It was observed that 1/32MIC erythromycin and 1/32MIC azithromycin upregulated the expression of fhaB in Tohama-I, whereas the expression of ptxS1 and prn significantly decreased in sub-MICs of erythromycin. In the Saadet strain, only ptxS1 was highly expressed at 1/16MIC azithromycin and erythromycin (p > 0.05). This is the first study to investigate the effect of sub-MIC antibiotics on the expression of virulence genes and biofilm-forming of B. pertussis.     

Characteristic analysis of Panton-Valentine leukocidin in children with invasive staphylococcus infection北大核心CSCD

Objective To evaluate the relationship between the Panton-Valentine leukocidin (pvl) strain and clinical characteristics, and to describe the molecular biological characteristics of invasive Staphylococcus aureus (S. aureus) infected clinical isolates. Methods The isolates of S. aureus caused by invasive infection were collected in Beijing Children's Hospital Affiliated to Capital Medical University from January 2016 to December 2019, and the clinical data of the corresponding children were collected retrospectively using electronic medical records. Multilocus sequence typing, spa typing and pvl gene were analyzed using the PCR. In addition, the minimum inhibitory concentrations (MIC) of antibiotics of all isolates were detected by the micro-broth dilution method, and the isolates were divided into the pvl+ and pvl- groups according to whether or not the S. aureus isolates carried pvl. The t test and the Mann-Whitney U test were used to compare the clinical symptoms between the pvl+ and pvl- groups. Chi-square test was used to compare the drug susceptibility between the two isolates. Results A total of 127 cases of invasive S. aureus infection were collected during the study period. The white blood cell count, neutrophil count, and C-reaction protein level in the pvl+ group were significantly higher than those in the pvl- group (P=0.001, P=0.001, P=0.005). The rate of pvl carrier was 44.9%. Among 57 pvl+ pathogenic strains, 64.9% (37/57) were MRSA. The multidrug resistance rate of pvl- isolates was higher than that of pvl+ isolates (70% vs. 49.12%, P=0.02). Conclusions In invasive S. aureus infection, pvl+ strain is associated with elevated inflammatory markers in children. the positive rate of pvl is higher in clinical isolates, and the multidrug resistance rate of pvl- S. aureus is higher. © 2022 Chinese Medical Association. All rights reserved.