Human genetic variation altering anthrax toxin sensitivity

The outcome of exposure to infectious microbes or their toxins is influenced by both microbial and host genes. Some host genes encode defense mechanisms, whereas others assist pathogen functions. Genomic analyses have associated host gene mutations with altered infectious disease susceptibility, but evidence for causality is limited. Here we demonstrate that human genetic variation affecting capillary morphogenesis gene 2 (CMG2), which encodes a host membrane protein exploited by anthrax toxin as a principal receptor, dramatically alters toxin sensitivity. Lymphoblastoid cells derived from a HapMap Project cohort of 234 persons of African, European, or Asian ancestry differed in sensitivity mediated by the protective antigen (PA) moiety of anthrax toxin by more than four orders of magnitude, with 99% of the cohort showing a 250-fold range of sensitivity. We find that relative sensitivity is an inherited trait that correlates strongly with CMG2 mRNA abundance in cells of each ethnic/geographical group and in the combined population pool (P = 4 × 10(-11)). The extent of CMG2 expression in transfected murine macrophages and human lymphoblastoid cells affected anthrax toxin binding, internalization, and sensitivity. A CMG2 single-nucleotide polymorphism (SNP) occurring frequently in African and European populations independently altered toxin uptake, but was not statistically associated with altered sensitivity in HapMap cell populations. Our results reveal extensive human diversity in cell lethality dependent on PA-mediated toxin binding and uptake, and identify individual differences in CMG2 expression level as a determinant of this diversity. Testing of genomically characterized human cell populations may offer a broadly useful strategy for elucidating effects of genetic variation on infectious disease susceptibility.     

牙周致病菌内毒素耐受的研究进展

内毒素耐受(endotoxin tolerance)是指先前的脂多糖(lipopolysaccharide,LPS)刺激使机体或体外培养的细胞对后续刺激反应性降低的一种现象,可能导致炎症因子释放的减少,进而在牙周炎发生发展过程中发挥重要作用。本文就牙周致病菌内毒素耐受的作用和机制的研究进展作一综述。     

Respiratory dendritic cells: mediators of tolerance and immunity

The respiratory tract is under constant bombardment from both innocuous and pathogenic material. The decision of how to respond to these challenges is mediated by a specialized set of antigen presenting cells within the lungs called dendritic cells (DC). Proper respiratory homeostasis requires that these respiratory DC (rDC) utilize both the local lung inflammatory environment as well as recognition of pathogen-specific patterns to determine whether to maintain homeostasis by either driving tolerance or immunity to the inhaled material. This review will focus on rDC and highlight how rDC regulate tolerance and immunity.     

Pathogens transmitted in animal feces in low- and middle-income countries

Animals found in close proximity to humans in low-and middle-income countries (LMICs) harbor many pathogens capable of infecting humans, transmissible via their feces. Contact with animal feces poses a currently unquantified—though likely substantial—risk to human health. In LMIC settings, human exposure to animal feces may explain some of the limited success of recent water, sanitation, and hygiene interventions that have focused on limiting exposure to human excreta, with less attention to containing animal feces.We conducted a review to identify pathogens that may substantially contribute to the global burden of disease in humans through their spread in animal feces in the domestic environment in LMICs. Of the 65 potentially pathogenic organisms considered, 15 were deemed relevant, based on burden of disease and potential for zoonotic transmission. Of these, five were considered of highest concern based on a substantial burden of disease for which transmission in animal feces is potentially important: Campylobacter, non-typhoidal Salmonella (NTS), Lassa virus, Cryptosporidium, and Toxoplasma gondii. Most of these have a wide range of animal hosts, except Lassa virus, which is spread through the feces of rats indigenous to sub-Saharan Africa. Combined, these five pathogens cause close to one million deaths annually. More than half of these deaths are attributed to invasive NTS. We do not estimate an overall burden of disease from improperly managed animal feces in LMICs, because it is unknown what proportion of illnesses caused by these pathogens can be attributed to contact with animal feces.Typical water quantity, water quality, and handwashing interventions promoted in public health and development address transmission routes for both human and animal feces; however, sanitation interventions typically focus on containing human waste, often neglecting the residual burden of disease from pathogens transmitted via animal feces. This review compiles evidence on which pathogens may contribute to the burden of disease through transmission in animal feces; these data will help prioritize intervention types and regions that could most benefit from interventions aimed at reducing human contact with animal feces.     

不同肺炎致病菌对夫西地酸钠的敏感性分析

目的分析研究不同肺炎致病菌对夫西地酸钠的敏感性。方法选取600例肺炎患者为研究对象,收集患者深部痰及呼吸道分泌物作为标本,根据《临床检验操作规程》和检测仪器、试剂的操作方法对不同肺炎致病菌进行鉴定、培养和药敏试验,观察不同肺炎致病菌对夫西地酸钠的敏感性。结果革兰阳性细菌均对夫西地酸钠具有敏感性,其中金黄色葡萄球菌、表皮葡萄球菌、肺炎链球菌及棒状杆菌敏感性较高,各菌种敏感率差异无统计学意义（P〉0．05）,甲型溶血性链球菌、肺炎链球菌的敏感率低于上述各菌种,其中甲型溶血性链球菌敏感率明显低于其他菌种敏感率,差异具有统计学意义（P〈0．05）。结论不同肺炎致病菌中,革兰阳性细菌均对夫西地酸钠具有较强的敏感性。     

ZnO Nanoparticles-Modified Dressings to Inhibit Wound Pathogens

Zinc oxide (ZnO) nanoparticles (NPs) have been investigated for various skin therapies in recent years. These NPs can improve the healing and modulate inflammation in the wounds, but the mechanisms involved in such changes are yet to be known. In this study, we have designed a facile ZnO nano-coated dressing with improved antimicrobial efficiency against typical wound pathogens involved in biofilm and chronic infections. ZnO NPs were obtained by hydrothermal method and characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Fourier-transform infrared spectroscopy. Antibacterial and antibiofilm effects were evaluated against laboratory and clinical isolates of significant Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Enterococcus faecalis) opportunistic pathogens, by quantitative methods. Our results have shown that the developed dressings have a high antibacterial efficiency after 6–24 h of contact when containing 0.6 and 0.9% ZnO NPs and this effect is similar against reference and clinical isolates. Moreover, biofilm development is significantly impaired for up to three days of contact, depending on the NPs load and microbial species. These results show that ZnO-coated dressings prevent biofilm development of main wound pathogens and represent efficient candidates for developing bioactive dressings to fight chronic wounds.     

2013-2014年荆州市第一人民医院神经外科病原菌的耐药性和抗菌药物用量的相关性分析

目的 分析荆州市第一人民医院神经外科病原菌的耐药性与抗菌药物用量的相关性,为临床合理用药提供参考。方法 统计2013年1月-2014年12月荆州市第一人民医院神经外科病原菌的分布及耐药性和抗菌药物的使用情况,并采用Pearson法对病原菌的耐药性与抗菌药物用量的相关性进行统计分析。结果 共分离出病原菌162株,主要来自痰标本(42.6%);其中革兰阴性菌以鲍曼不动杆菌、铜绿假单胞菌为主,革兰阳性菌以金黄色葡萄球菌为主;鲍曼不动杆菌对多数抗菌药物均耐药,而铜绿假单胞菌对常用抗生素仍保持较高的敏感性,金黄色葡萄球菌除对万古霉素、复方磺胺、利奈唑胺仍保持较高的敏感性外,对其余试验药物的耐药率较高。抗菌药物的使用以头孢唑啉、头孢西丁、左氧氟沙星的用药频度(DDDs)较高。鲍曼不动杆菌、铜绿假单胞菌对头孢他啶、左氧氟沙星、美罗培南的耐药率与DDDs显著相关;金黄色葡萄球菌对左氧氟沙星、头孢西丁的耐药率与DDDs显著相关。结论 荆州市第一人民医院神经外科鲍曼不动杆菌及金黄色葡萄球菌的耐药率较高,除需严格控制抗菌药物的合理应用外,全面落实医院感染防控措施至关重要。     

Raw Milk Consumption among Patients with Non–Outbreak-related Enteric Infections,Minnesota, USA, 2001–2010

Raw milk has frequently been identified as the source of foodborne illness outbreaks; however, the number of illnesses ascertained as part of documented outbreaks likely represents a small proportion of the actual number of illnesses associated with this food product. Analysis of routine surveillance data involving illnesses caused by enteric pathogens that were reportable in Minnesota during 2001–2010 revealed that 3.7% of patients with sporadic, domestically acquired enteric infections had reported raw milk consumption during their exposure period. Children were disproportionately affected, and 76% of those <5 years of age were served raw milk from their own or a relative’s farm. Severe illness was noted, including hemolytic uremic syndrome among 21% of Escherichia coli O157–infected patients reporting raw milk consumption, and 1 death was reported. Raw milk consumers, potential consumers, and policy makers who might consider relaxing regulations regarding raw milk sales should be educated regarding illnesses associated with raw milk consumption.