Distinct roles of secreted HtrA proteases from gram-negative pathogens in cleaving the junctional protein and tumor suppressor E-cadherin

The periplasmic chaperone and serine protease HtrA is important for bacterial stress responses and protein quality control. Recently, we discovered that HtrA from Helicobacter pylori is secreted and cleaves E-cadherin to disrupt the epithelial barrier, but it remained unknown whether this maybe a general virulence mechanism. Here, we show that important other pathogens including enteropathogenic Escherichia coli, Shigella flexneri, and Campylobacter jejuni, but not Neisseria gonorrhoeae, cleaved E-cadherin on host cells. HtrA deletion in C. jejuni led to severe defects in E-cadherin cleavage, loss of cell adherence, paracellular transmigration, and basolateral invasion. Computational modeling of HtrAs revealed a conserved pocket in the active center exhibiting pronounced proteolytic activity. Differential E-cadherin cleavage was determined by an alanine-to-glutamine exchange in the active center of neisserial HtrA. These data suggest that HtrA-mediated E-cadherin cleavage is a prevalent pathogenic mechanism of multiple gram-negative bacteria representing an attractive novel target for therapeutic intervention to combat bacterial infections.     

Dynamic interplay between adhesion surfaces in carcinomas:Cell-cell and cell-matrix crosstalk

Cell-cell and cell-matrix signaling and communication between adhesion sites involve mechanisms which are required for cellular functions during normal development and homeostasis; however these cellular functions and mechanisms are often deregulated in cancer. Aberrant signaling at cell-cell and cell-matrix adhesion sites often involves downstream mediators including Rho GTPases and tyrosine kinases. This review discusses these molecules as putative mediators of cellular crosstalk between cell-cell and cell-matrix adhesion sites, in addition to their attractiveness as therapeutic targets in cancer. Interestingly, inter-junctional crosstalk mechanisms are frequently typified by the way in which bacterial and viral pathogens opportunistically infect or intoxicate mammalian cells. This review therefore also discusses the concept of learning from pathogen-host interaction studies to better understand coordinated communication between cell-cell and cell-matrix adhesion sites, in addition to highlighting the potential therapeutic usefulness of exploiting pathogens or their products to tap into inter-junctional crosstalk. Taken together, we feel that increased knowledge around mechanisms of cell-cell and cell-matrix adhesion site crosstalk and consequently a greater understanding of their therapeutic targeting offers a unique opportunity to contribute to the emerging molecular revolution in cancer biology.     

Cellular Automata Modeling of Pulmonary Inflammation

Better understanding of the acute/chronic inflammation in airways is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. Local lung inflammation is triggered by many mechanisms within the lung, including pathogens. In this study, a cellular automata based model (CA) for pulmonary inflammation that incorporates biophysical processes during inflammatory responses was developed. The developed CA results in three possible outcomes related to homeostasis (healing), persistent infection, and resolved infection with high inflammation (inflamed state). The results from the model are validated qualitatively against other existing computational models. A sensitivity analysis was conducted on the model parameters and the outcomes were assessed. Overall, the model results showed possible outcomes that have been seen in clinical practice and animal models. The present model can be extended to include inflammation resulting from damage tissue and eventually to model inflammation resulting from acute lung injury and multiple organ dysfunction syndromes in critical illness and injury.     

1281例泌尿生殖道感染患者的病原体分析

目的了解汕头地区泌尿生殖道炎患者病原体感染情况。方法应用培养、衣原体快速免疫测定法及镜检,对性病科和妇科门诊1281例泌尿生殖道感染患者进行淋球菌(NG)、沙眼衣原体(Ct)、解脲支原体(Uu)、人型支原体(Mh)、念珠菌(Cd)和滴虫检测。结果男577例．检出262株病原体,女704例．检出656株病原体。6种病原体阳性率男女性分别为(括号内为女性)：NG3．5％(3．1％)、Ct11．6％(10．9％)、Uu24．1％(50．6％)、Mh1．5％(6．3％)、Cd4．5％(20．2％)和滴虫17％(2．0％),感染率为37．3％(65．2％),混合感染占19．1％(37．3％)。结论汕头地区非淋球菌性和条件致病性病原体Ct、Uu和Cd占主导,混合感染普遍．男、女性感染情况除NG、Ct外,女性明显高于男性。     

The role of constructed wetlands in secondary effluent treatment and water reuse in subtropical and arid Australia

Water reclamation and reuse is being actively promoted in Australia. In Queensland, surface-flow constructed wetlands with a diversity of macrophyte types offer the greatest potential for effluent polishing. Constructed wetlands in subtropical climates in coastal regions and arid climates in inland western regions are conducive to high macrophyte growth rates and nutrient removal, in particular nitrogen, producing an effluent suitable for irrigation, restoration of wetlands and/or release into natural waterways. Faecal-coliform removal is also high, producing effluent with <1000 cfu/100 mL and as low as 100 cfu/100 mL, acceptable for agricultural irrigation. Constructed wetlands can be designed to maximise the removal of both nutrients and pathogens by enhancing macrophyte diversity and natural disinfection processes by incorporating lagoons, shallow-water wetlands and subsurface-flow wetlands into the treatment train. Surface-flow wetlands can also be designed to minimise mosquito breeding by increasing macro-invertebrate predators, thereby alleviating community concerns about potential health risks. This paper addresses the role of constructed wetlands in nutrient and pathogen removal in Queensland's wetlands, and presents three case studies with respect to effluent reuse.     

Livestock waste treatment systems for reducing environmental exposure to hazardous enteric pathogens: Some considerations

Intensive livestock production systems produce significant quantities of excreted material that must be managed to protect water, air, and crop quality. Many jurisdictions mandate how livestock wastes are managed to protect adjacent water quality from microbial and chemical contaminants that pose an environmental and human health challenge. Here, we consider innovative livestock waste treatment systems in the context of multi-barrier strategies for protecting water quality from agricultural contamination. Specifically, we consider some aspects of how enteric bacterial populations can evolve during manure storage, how their fate following land application of manure can vary according to manure composition, and finally the challenge of distinguishing enteric pathogens of agricultural provenance from those of other sources of fecal pollution at a policy-relevant watershed scale. The beneficial impacts of livestock waste treatment on risk to humans via exposure to manured land are illustrated using quantitative microbial risk assessment (QMRA) scenarios. Overall, innovative livestock treatment systems offer a crucially important strategy for making livestock wastes more benign before they are released into the broader environment.     

Management of plant health risks associated with processing of plant-based wastes: A review

The rise in international trade of plants and plant products has increased the risk of introduction and spread of plant pathogens and pests. In addition, new risks are arising from the implementation of more environmentally friendly methods of biodegradable waste disposal, such as composting and anaerobic digestion. As these disposal methods do not involve sterilisation, there is good evidence that certain plant pathogens and pests can survive these processes. The temperature/time profile of the disposal process is the most significant and easily defined factor in controlling plant pathogens and pests. In this review, the current evidence for temperature/time effects on plant pathogens and pests is summarised. The advantages and disadvantages of direct and indirect process validation for the verification of composting processes, to determine their efficacy in destroying plant pathogens and pests in biowaste, are discussed. The availability of detection technology and its appropriateness for assessing the survival of quarantine organisms is also reviewed.     

一株病原拮抗野生菌株的筛选、鉴定及其发酵工艺优化

为获得广谱抗菌功能野生菌株并提高其发酵产物中抗菌物质的含量。采用管碟法和菌丝生长速率法筛选功能菌株,ITS序列分析鉴定功能菌株,通过响应面法和正交设计优化发酵生产抗菌物质的工艺。筛选到一株强效、广谱抗菌功能菌株,鉴定为Cerrena sp.,其发酵产物对金黄色葡萄球菌、大肠杆菌、白色念珠菌、枯草芽孢杆菌和水稻纹枯病菌有显著拮抗作用。该菌株的摇甁发酵配方及培养条件为：马铃薯13.99 g/L,蔗糖 41.58 g/L,VB1 0.027 g/L,麸皮7 g/L,KH₂PO₄ 2 g/L,MgSO₄·7H₂O 2 g/L;摇床温度28 ℃、发酵周期10 d、种龄4 d、接种量8%、初始pH为5.0、装液量110 ml/250 ml。该菌株有明显抑菌活性,发酵工艺优化后抗菌活性提高了30.37%,为该菌株今后的应用、抗菌剂的分离提纯和产业化提供了实验依据。     

南方九孔鲍鲍苗掉板病原菌的药敏测定

为提高鲍鱼培苗的成活率,对分离自广东汕尾一养殖场鲍苗掉板池中(包括水、藻膜和变白鲍苗)的、经回归感染试验证明为致病菌的菌株进行了鉴定和药物敏感性测定。API鉴定表明,这些致病菌株由Vibrio alginolyticus,Vibrio cholerae,Vibrio parahaemolyticus等组成,其中弧菌17株,约占总分离菌株的50％,而溶藻弧菌则为弧菌的优势菌株,有11株,约占弧菌总数的70％。药敏结果显示,绝大多数菌株对链霉素、红霉素和庆大霉素敏感;相反,四环素和新生霉素则对它们没有作用或不敏感。     

Impacts of naturally-occurring soil fungi on seeds of meadow plants

Although soil fungi may represent an ecologically important cause of mortality of buried seeds, few studies have provided direct evidence of the pathogenicity of fungi colonizing seeds in natural habitats. In response, we conducted a series of experiments to investigate the impacts of soil fungi from a range of habitats on seeds of meadow plants. We compared the survival of seeds of four grasses in five habitats, and isolated fungi from these seeds. We then tested the pathogenicity of selected isolates against two standard sets of plant species: the original four grasses and a broad range of old field species. We found that the soil community contained a large variety of seed-colonizing fungi. Some, but not all, examples of these fungi caused seed mortality; others may be harmless commensals. Some of these isolates negatively affected a broad range of plant species, but others had a more restricted host range; as a result, pathogenicity varied depending upon the particular plant-fungus combination. Few between-habitat differences in seed survival were detected. Our results demonstrate that fungal seed pathogens are common, ubiquitous, and potentially lethal, but that their effects depend on the particular combination of fungus and plant species considered. This revised version was published online in June 2006 with corrections to the Cover Date.