ISSN 1673-6184 CN 31-1966/R
2012年对《微生物与感染》来说是不寻常的一年，因为本刊的“姐妹”刊——Emerging Microbes and Infections（EMI，http://www.emi2012.org）将作为Nature Publishing Group（NPG）的成员于今年7月在线发表。EMI是国际化刊物，其编委会由86名国际知名的微生物与临床感染性疾病专家组成，其中50%为境外成员。因此，通过国内外两本杂志相互促进，期望本刊在学术水平和质量上有一个飞跃。......
Legionella pneumophila, the causative agent of Legionnaires' disease, has been recognized as a major health problem responsible for an estimated number of 15 000-30 000 cases of severe pneumonia per year in Germany alone. Despite of the high clinical relevance, many aspects of the intracellular life-cycle of Legionella, especially details on interactions with host cells, are not well understood. Structural information on virulence proteins helps unravel basal pathogenicity mechanisms and is a prerequisite for the rational development of effective drug molecules. Here we discuss structures of three important virulence proteins of Legionella that have been determined in our laboratory. The structure of the macrophage infectivity potentiator (Mip) protein of Legionella pneumophila is the first of a novel subgroup within the family of FK506-binding protein (FKBP) peptidyl-prolyl cis/trans isomerases. On the basis of the Mip structure, promising antibacterial agents are being designed. Recently, structures of two equally exciting Legionella proteins have been reported. The ferrous iron transport protein FeoB is a transmembrane protein responsible for Fe2+ aquisition after entry of the pathogen into the host cell. The structure of the cytoplasmic domain of ferrous iron transporter (FeoB) provides insights into the family of prokaryotic G proteins and allows a detailed comparison with structures of related FeoBs. Furthermore, the characterization of DegQ, a periplasmatic chaperone-protease involved in protein quality control represents an intriguing example of how enzymatic activity is regulated by oligomerization as well as by an intrinsic loop activation cascade, depending on subtle conformational rearrangements.
A genome-wide association study recently showed that genetic variants in human leukocyte antigen (HLA)-DP loci were strongly associated with a risk of persistent infection of hepatitis B virus (HBV) in Japanese and Thai individuals and variants in interleukin 28B (IL-28B) have been associated with responses to anti-hepatitis C virus (HCV) treatment. The aim of this study was to investigate whether the HLA-DP loci and IL-28B were associated with different outcomes of chronic HBV infection (CHB) in Chinese subjects. The rs9277535 near HLA-DPB1，rs3077 near HLA-DPA1, and rs12979860 genotype near IL28B were genotyped by direct sequencing in 185 CHB patients and 193 self-limited hepatitis B virus (SLHBV)-infected subjects who recovered from HBV infection. The rs9277535 near HLA-DPB1 was strongly associated with CHB (P=0.0000181, OR=1.905). This association was observed independent of HBV e antigen (HBeAg) status and HBV viral loads in HBeAg-positive patients (P=0.0004, OR=1.956), in HBeAg-negative patients (P=0.0009, OR=1.857), and in HBeAg-negative individuals without detectable levels of HBV DNA in serum (P=0.0011, OR=2.05). The rs3077 near HLA-DPA1 was associated with CHB (P=0.0206, OR=0.6865) and HBeAg-positive infection status (P=0.0143, OR=0.6047). Meanwhile, a genetic variation of insertion-deletion (INDEL) polymorphism (rs361527, -/ATAAATGTTGA) near HLA-DPA1 was found to be associated with CHB (P=0.0307, OR=0.7028) and HBeAg-positive CHB infection status (P=0.0233, OR=0.619). However，the rs12979860 genotype near IL28B had no correlation with CHB. This study demonstrated that in the Han Chinese populations, HLA DP loci, but not IL-28B, was associated with persistence of infection in different outcomes of HBV infected patients; however, the mechanism needs to be further investigated.
本文旨在分析含红荧光蛋白mCherry基因的重组柯萨奇病毒B组3型（coxsackievirus B3，CVB3）基因组的稳定性。用重组质粒pCVB3-mCherry转染HeLa细胞，观察细胞病变和mCherry的表达。收获病毒后，用噬斑实验纯化病毒并测定病毒毒力。将重组病毒CVB3-mCherry在HeLa细胞中连续传代，提取第2~6代重组病毒总RNA，经反转录-聚合酶链反应（RT-PCR）扩增出报告基因mCherry及CVB3部分序列，进行测序分析。结果表明， CVB3-mCherry转染的HeLa细胞出现细胞病变并表达红荧光蛋白mCherry；从第2代开始， CVB3-mCherry出现报告基因mCherry及部分CVB VP4基因序列丢失，基因序列丢失导致病毒开放读码框架移位。本研究表明，mCherry基因序列的插入导致CVB3基因组不稳定，随着病毒的传代逐渐丢失插入的报告基因mCherry及CVB3基因组的部分序列，病毒读码框移位，产生致死性突变株。因此，应用CVB3-mCherry时，病毒的传代次数应不超过2代，否则应重新从重组质粒中收获病毒，并对每代重组病毒进行纯化和毒力测定。
为分析我国社区儿童皮肤感染来源的金黄色葡萄球菌流行特点及耐药现状，明确社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)中mecA基因携带情况及葡萄球菌盒式染色体SCCmec基因分型情况，并为临床治疗选择合理而有效的治疗方案提供依据，本文对全国13家儿童医院1 416例皮肤感染患儿的皮损分泌物进行细菌培养，应用琼脂稀释法检测16种抗生素对培养出的金黄色葡萄球菌的最小抑菌浓度，应用聚合酶链式反应对CA-MRSA进行mecA基因检测及SCCmec基因分型。从1 416例患儿皮损中培养出金黄色葡萄球菌1 043株，对16种抗生素的药敏试验结果显示，耐药率前3位依次为红霉素97.3%，青霉素96.7%，克林霉素89%，其次为四环素42.2%、氯霉素15%、庆大霉素9.8%、环丙沙星6.6%、复方新诺明4.6%、苯唑西林3.4%、头孢呋辛3.1%、利福平2.4%、头孢曲松1.7%、头孢唑啉1.6%、夫西地酸1.3%、莫匹罗星0.8%。CA-MRSA分离率为3.4%，各地区均未发现万古霉素耐药或中介耐药菌株。35株CA-MRSA均携带mecA基因，SCCmec基因分型结果为Ⅳ型14株（40%）、Ⅴ型19株（54.3%）、未定型2株（5.7%）。本研究提示，治疗我国社区儿童皮肤金黄色葡萄球菌感染性疾病，仍首选全身应用耐青霉素酶的半合成青霉素和第1、2代头孢菌素，其他可选择的有夫西地酸、复方新诺明、利福平、万古霉素，外用治疗选择莫匹罗星，具有较好的抗菌活性。我国儿童CA-MRSA中mecA携带率100%，SCCmec Ⅳ和Ⅴ型为主要类型。
白假丝酵母（又称白念珠菌）是人体重要的条件致病真菌。在正常人体中，白假丝酵母是一种无害共生真菌；在免疫力低下人群中，白假丝酵母可引起假丝酵母病，轻者可导致黏膜感染，重者可发展为系统疾病，直至危及生命。白假丝酵母从酵母态至菌丝态的形态转变是极其重要的致病因素之一。BDSF是小分子短链脂肪酸，由Burkholderia cenocepacia分泌产生。酵母态白假丝酵母，在BDSF≥30 μmol/L时因菌丝生长受强烈抑制，无法由酵母相向菌丝相转变。而菌丝相白假丝酵母，当BDSF在30 μmol/L和60 μmol/L时，菌丝进一步生长并产生分支，但随菌丝分支生长，新生的分支菌丝不断转变为酵母态；当BDSF增加至120 μmol/L时，菌丝生长和分支状况几乎完全受抑制。由此可见，BDSF不仅强烈抑制菌丝生长，还可促使新生的菌丝态向酵母态转化。
丝氨酸/苏氨酸蛋白激酶（STPK）是一类真核细胞样的蛋白激酶，是生长和代谢的重要调节因子，参与分枝杆菌多种细胞活动（如细胞及菌落形态、葡萄糖和谷氨酰胺转运、吞噬体溶酶体融合、转录因子活性等）的调节。结核分枝杆菌编码产生11种STPK（PknA、PknB、PknD~PknL），可分为5群（ABL群、HED群、FIJ群、PknG和PknK）。ABL群 STPK中的 PknA和 PknB主要与细胞形态有关，PknL可磷酸化DNA结合蛋白Rv2175c；HED群参与细菌的多种重要生理活动并与致病性密切相关；FIJ群的PknF可能与葡萄糖转运和细菌分裂有关，PknI可能参与调节有害环境中的细菌生长，PknJ可磷酸化多种功能蛋白, 进而影响细菌代谢活动；PknG参与谷氨酸盐/谷氨酰胺代谢并与致病性有关；PknK可能对调节体内环境压力下的生长起重要作用。综上所述，STPK可能参与结核分枝杆菌致病过程中的多个环节，但详细机制还不清楚，仍需进一步研究。
