The good viruses: viral mutualistic symbioses

Although viruses are most often studied as pathogens, many are beneficial to their hosts, providing essential functions in some cases and conditionally beneficial functions in others. Beneficial viruses have been discovered in many different hosts, including bacteria, insects, plants, fungi and animals. How these beneficial interactions evolve is still a mystery in many cases but, as discussed in this Review, the mechanisms of these interactions are beginning to be understood in more detail.     

Micro-managing arthropod invasions: eradication and control of invasive arthropods with microbes

Non-indigenous arthropods are increasingly being introduced into new areas worldwide and occasionally they cause considerable ecological and economic harm. Many invasive arthropods particularly pose problems to areas of human habitation and native ecosystems. In these cases, the use of environmentally benign materials, such as host-specific entomopathogens, can be more desirable than broader spectrum control tactics that tend to cause greater non-target effects. The majority of successful eradication programs using arthropod pathogens have targeted invasive Lepidoptera with Bacillus thuringiensis kurstaki (Btk), such as eradication efforts against the gypsy moth, Lymantria dispar (L.), in North America and New Zealand. Both Btk and Lymantria dispar nucleopolyhedrovirus have been successfully used in efforts to limit the spread of L. dispar in the United States. For invasive arthropod species that are well established, suppression programs have successfully used arthropod-pathogenic viruses, bacteria, fungi and nematodes for either short- or long-term management. We will summarize the use of pathogens and nematodes in invasive arthropod management programs within a general context, and compare the use of microbes in gypsy moth management with diverse microbes being developed for use against other invasive arthropods.     

Targeting the glycans of glycoproteins: a novel paradigm for antiviral therapy

Several chronic viral infections (such as HIV and hepatitis C virus) are highly prevalent and are a serious health risk. The adaptation of animal viruses to the human host, as recently exemplified by influenza viruses and the severe acute respiratory syndrome coronavirus, is also a continuous threat. There is a high demand, therefore, for new antiviral lead compounds and novel therapeutic concepts. In this Review, an original therapeutic concept for suppressing enveloped viruses is presented that is based on a specific interaction of carbohydrate-binding agents (CBAs) with the glycans present on viral-envelope glycoproteins. This approach may also be extended to other pathogens, including parasites, bacteria and fungi.     

A global view on fungal infections in humans and animals: opportunistic infections and microsporidioses

After cardiovascular diseases, infectious diseases are the second most common cause of death worldwide. Although these infections are caused mainly by viruses or bacteria, a systematically growing prevalence of human and animal opportunistic fungal infections is noticeable worldwide. More attention is being paid to this problem, especially due to the growing frequency of recalcitrant and recurrent mycoses. The latter are classically divided into superficial, which are the most common type, subcutaneous, and systemic. This work discusses opportunistic fungal pathogens without proven horizontal transmission between different animal species including humans and microsporidia as spore-forming unicellular parasites related to fungi; however, with a yet undetermined taxonomic position. The review also mentions aetiological agents, risk factors, epidemiology, geographical distribution, and finally symptoms characteristic for individual disease entities. This paper provides insight into fungal infections from a global perspective and simultaneously draws attention to emerging pathogens, whose prevalence is continuously increasing. Finally, this work also takes into consideration the correct nomenclature of fungal disease entities and the importance of secondary metabolites in the pathogenesis of fungal infections.     

Current developments in microbial control of insect pests and prospects for the early 21st century

The role of microbial control in crop and forest protection and the abatement of insects of medical and veterinary importance has expanded considerably with the discovery and development of new microbial control agents and genetic improvement in bacterial and viral pathogens, and improvements in formulation, application options and compatibility with other interventions. A synopsis of the literature regarding the current use of bacteria, viruses, fungi, protozoans and nematodes as microbial control agents is presented along with speculation on their potential in the early 21st century. The most widely used of all microbial control agents isBacillus thuringiensis. The isolation within the past two decades of new strains that are larvicidal for certain Diptera and Coleoptera has increased the utility of the bacterium considerably. Further improvements in efficacy and broadening of its host range are in progress with the isolation of strains with new toxins and the manipulation ofB. thuringiensis genes that encode toxin production using both recombinant and nonrecombinant methods. Genetic manipulation of these genes has also enabled their incorporation into crop plants. The development and commercial availability of entomopathogenic nematodes in the families Steinernematidae and Heterorhabditidae expands the options for the control of insects, especially those with soil inhabiting stages. The results of natural epizootics of fungi and viruses often obviate the requirement for additional interventions. Breakthroughs in understanding the genetics ofBaculovirus and subsequent gene manipulation have increased their virulence and utility. Improved production methods that utilize insect cell culture technology may enable affordable use ofBaculovirus in the not too distant future. Fungi continue to offer the only control options using entomopathogens against plant sucking insects. Although fungi have great potential for development as microbial control agents, only a few have been used on an operational scale. Some factors that might limit the full range of entomopathogen potential, including development of resistance, are discussed. Because of their selectivity and minimal environmental impact, microbial control agents will be ideal components of integrated pest management programs in the early 21st century and beyond. However, if they are used merely as replacements for chemical pesticides, then eventually these agents will face some of the same fate as the chemicals they replace, particularly with respect to resistance.     

Ibis T5000: a universal biosensor approach for microbiology

We describe a new technology, the Ibis T5000, for the identification of pathogens in clinical and environmental samples. The Ibis T5000 couples nucleic acid amplification to high-performance electrospray ionization mass spectrometry and base-composition analysis. The system enables the identification and quantification of a broad set of pathogens, including all known bacteria, all major groups of pathogenic fungi and the major families of viruses that cause disease in humans and animals, along with the detection of virulence factors and antibiotic resistance markers.     

Enzyme-based formulations for decontamination: current state and perspectives

Development of noncorrosive, cost-effective, environmentally benign, and broad-spectrum antimicrobial formulations is necessary for clinical, industrial, and domestic purposes. Many current decontaminating formulations are effective, but they require the use of strong oxidizing agents or organic solvents that have deleterious effects on human health and the surrounding environment. The emergence of antibiotic-resistant pathogens has motivated researchers to develop enzyme-based self-decontaminating formulations as alternatives to such chemical decontamination approaches. Hydrolytic and oxidative enzymes can be used to deactivate pathogens, including bacteria, spores, viruses, and fungi. Laccases, haloperoxidases, and perhydrolases catalyze the generation of biocidal oxidants, such as iodine, bromine, hypohalous acid (e.g., HOCl or HOBr), and peracetic acid. These oxidants have broad-spectrum antimicrobial activity. Due to the multi-pathway action of these oxidants, it has proven extremely difficult for microbes to gain resistance. Thus far, few examples have been reported on enzyme-based antimicrobial formulations. For these reasons, various enzyme-containing antimicrobial formulations are highlighted in this review.     

Risk factors for human disease emergence

A comprehensive literature review identifies 1415 species of infectious organism known to be pathogenic to humans, including 217 viruses and prions, 538 bacteria and rickettsia, 307 fungi, 66 protozoa and 287 helminths. Out of these, 868 (61%) are zoonotic, that is, they can be transmitted between humans and animals, and 175 pathogenic species are associated with diseases considered to be 'emerging'. We test the hypothesis that zoonotic pathogens are more likely to be associated with emerging diseases than non-emerging ones. Out of the emerging pathogens, 132 (75%) are zoonotic, and overall, zoonotic pathogens are twice as likely to be associated with emerging diseases than non-zoonotic pathogens. However, the result varies among taxa, with protozoa and viruses particularly likely to emerge, and helminths particularly unlikely to do so, irrespective of their zoonotic status. No association between transmission route and emergence was found. This study represents the first quantitative analysis identifying risk factors for human disease emergence.     

Zebrafish RNase T2 genes and the evolution of secretory ribonucleases in animals

Background  

Members of the Ribonuclease (RNase) T2 family are common models for enzymological studies, and their evolution has been well characterized in plants. This family of acidic RNases is widespread, with members in almost all organisms including plants, animals, fungi, bacteria and even some viruses. While several biological functions have been proposed for these enzymes in plants, their role in animals is unknown. Interestingly, in vertebrates most of the biological roles of plant RNase T2 proteins are carried out by members of a different family, RNase A. Still, RNase T2 proteins are conserved in these animals     

Antibody-Based Resistance to Plant Pathogens

Plant diseases are a major threat to the world food supply, as up to 15% of production is lost to pathogens. In the past, disease control and the generation of resistant plant lines protected against viral, bacterial or fungal pathogens, was achieved using conventional breeding based on crossings, mutant screenings and backcrossing. Many approaches in this field have failed or the resistance obtained has been rapidly broken by the pathogens. Recent advances in molecular biotechnology have made it possible to obtain and to modify genes that are useful for generating disease resistant crops. Several strategies, including expression of pathogen-derived sequences or anti-pathogenic agents, have been developed to engineer improved pathogen resistance in transgenic plants. Antibody-based resistance is a novel strategy for generating transgenic plants resistant to pathogens. Decades ago it was shown that polyclonal and monoclonal antibodies can neutralize viruses, bacteria and selected fungi. This approach has been improved recently by the development of recombinant antibodies (rAbs). Crop resistance can be engineered by the expression of pathogen-specific antibodies, antibody fragments or antibody fusion proteins. The advantages of this approach are that rAbs can be engineered against almost any target molecule, and it has been demonstrated that expression of functional pathogen-specific rAbs in plants confers effective pathogen protection. The efficacy of antibody-based resistance was first shown for plant viruses and its application to other plant pathogens is becoming more established. However, successful use of antibodies to generate plant pathogen resistance relies on appropriate target selection, careful antibody design, efficient antibody expression, stability and targeting to appropriate cellular compartments.     

Update on the proteomics of major arthropod vectors of human and animal pathogens

Vector‐borne diseases (VBDs) are defined as infectious diseases of humans and animals caused by pathogenic agents such as viruses, protists, bacteria, and helminths transmitted by the bite of blood‐feeding arthropod (BFA) vectors. VBDs represent a major public health threat in endemic areas, generally subtropical zones, and many are considered to be neglected diseases. Genome sequencing of some arthropod vectors as well as modern proteomic and genomic technologies are expanding our knowledge of arthropod–pathogen interactions. This review describes the proteomic approaches that have been used to investigate diverse biological questions about arthropod vectors, including the interplay between vectors and pathogens. Proteomic studies have identified proteins and biochemical pathways that may be involved in molecular crosstalk in BFA‐pathogen associations. Future work can build upon this promising start and functional analyses coupled with interactome bioassays will be carried out to investigate the role of candidate peptides and proteins in BFA‐human pathogen associations. Dissection of the host–pathogen interactome will be key to understanding the strategies and biochemical pathways used by BFAs to cope with pathogens.     

A highly virulent pathogen, Aeromonas hydrophila, from the freshwater crayfish Pacifastacus leniusculus

Aeromonas spp. are characteristic bacteria of freshwaters and many of them can be components of the bacterial flora of aquatic animals and may become pathogens on animals including humans. In this study Aeromonas hydrophila was isolated from the freshwater crayfish, Pacifastacus leniusculus, and was found to be a highly pathogenic bacterium among many isolated bacteria. Mortality reached 100% within 6 h when 200 μl of 1.24 × 10⁷ CFU/ml was applied by injection. Histopathological studies of moribund crayfish showed that extensive necrotic nuclei and clump-infiltrated hemocytes were found in observed tissues including gill, heart, hepatopancreas and the circulatory system. To verify how crayfish are susceptible to this bacterium, crude extracellular products (ECPs) obtained from culture supernatant of A. hydrophila was studied either in vivo or in vitro. ECPs (200 μl) were able to kill crayfish by injection. In an in vitro study, ECPs induced cytotoxicity of hemocytes as well as hematopoietic cells in a dose- and time-dependent manner after 30 min post inoculation. Two genes coding for endotoxins were also found in this isolate of A. hydrophila. This indicates that the bacterial endotoxins are the causative agents of crayfish mortality. Moreover, the effect of temperature on the infectivity of A. hydrophila to crayfish was also studied. At 4 °C, all crayfish survived, whereas at 20 °C the animals died rapidly after bacterial challenge. At this low temperature A. hydrophila did not replicate or replicated at a very low degree and hence crayfish could probably mount effective cellular reactions towards A. hydrophila.     

An overview of antifungal peptides derived from insect

Fungi are not classified as plants or animals. They resemble plants in many ways but do not produce chlorophyll or make their own food photosynthetically like plants. Fungi are useful for the production of beer, bread, medicine, etc. More complex than viruses or bacteria; fungi can be destructive human pathogens responsible for various diseases in humans. Most people have a strong natural immunity against fungal infection. However, fungi can cause diseases when this immunity breaks down. In the last few years, fungal infection has increased strikingly and has been accompanied by a rise in the number of deaths of cancer patients, transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients owing to fungal infections. The growth rate of fungi is very slow and quite difficult to identify. A series of molecules with antifungal activity against different strains of fungi have been found in insects, which can be of great importance to tackle human diseases. Insects secrete such compounds, which can be peptides, as a part of their immune defense reactions. Active antifungal peptides developed by insects to rapidly eliminate infectious pathogens are considered a component of the defense munitions. This review focuses on naturally occurring antifungal peptides from insects and their challenges to be used as armaments against human diseases.     

Trichoderma/pathogen/plant interaction in pre-harvest food security

Large losses before crop harvesting are caused by plant pathogens, such as viruses, bacteria, oomycetes, fungi, and nematodes. Among these, fungi are the major cause of losses in agriculture worldwide. Plant pathogens are still controlled through application of agrochemicals, causing human disease and impacting environmental and food security. Biological control provides a safe alternative for the control of fungal plant pathogens, because of the ability of biocontrol agents to establish in the ecosystem. Some Trichoderma spp. are considered potential agents in the control of fungal plant diseases. They can interact directly with roots, increasing plant growth, resistance to diseases, and tolerance to abiotic stress. Furthermore, Trichoderma can directly kill fungal plant pathogens by antibiosis, as well as via mycoparasitism strategies. In this review, we will discuss the interactions between Trichoderma/fungal pathogens/plants during the pre-harvest of crops. In addition, we will highlight how these interactions can influence crop production and food security. Finally, we will describe the future of crop production using antimicrobial peptides, plants carrying pathogen-derived resistance, and plantibodies.     

Diseases of Mites

An overview is given of studies on diseases of mites. Knowledge of diseases of mites is still fragmentary but in recent years more attention has been paid to acaropathogens, often because of the economic importance of many mite species. Most research on mite pathogens concerns studies on fungal pathogens of eriophyoids and spider mites especially. These fungi often play an important role in the regulation of natural mite populations and are sometimes able to decimate populations of phytophagous mites. Studies are being conducted to develop some of these fungi as commercial acaricides.Virus diseases are known in only a few mites, namely, the citrus red mite and the European red mite. In both cases, non-occluded viruses play an important role in the regulation of mite populations in citrus and peach orchards, respectively, but application of these viruses as biological control agents does not seem feasible. A putative iridovirus has been observed in association with Varroa mites in moribund honeybee colonies. The virus is probably also pathogenic for honeybees and may be transmitted to them through this parasitic mite.Few bacteria have been reported as pathogens of the Acari but in recent years research has been concentrated on intracellular organisms such as Wolbachia that may cause distorted sex ratios in offspring and incompatibility between populations. The role of these organisms in natural populations of spider mites is in particular discussed. The effect of Bacillus thuringiensis on mites is also treated in this review, although its mode of action in arthropods is mainly due to the presence of toxins and it is, therefore, not considered to be a pathogen in the true sense of the word.Microsporidia have been observed in several mite species especially in oribatid mites, although other groups of mites may also be affected. In recent years, Microsporidia infections in Phytoseiidae have received considerable attention, as they are often found in mass rearings of beneficial arthropods. They affect the efficacy of these predators as biological control agent of insect and mite pests. Microsporidia do not seem to have potential for biological control of mites.     

TGF-beta in infections and infectious diseases

Since it was first described as having the ability to inhibit macrophage activation, transforming growth factor-beta (TGF-beta) has been analyzed for its role in regulating immune responses to a variety of pathogens, including viruses, bacteria, yeast, and protozoa. Most of the studies have involved organisms that infect macrophages, and this discussion will attempt to highlight these findings. Perhaps the most work has been performed with protozoan pathogens, including Trypanosoma cruzi and a variety of Leishmania species, so the discussion will begin with these organisms. Other studies have focused on mycobacteria and viruses, including human immunodeficiency virus, so these areas will also be emphasized in the discussion. For the most part, investigators have reported that TGF-beta has, as expected, a negative influence on host responses and a beneficial effect on the survival and growth of intracellular pathogens. However, other studies have found that TGF-beta may have a positive or beneficial effect in some models of infection. This review will attempt to highlight studies and conclusions on the roles of TGF-beta in infection.     

抗菌肽及其临床应用研究进展

抗菌肽是生物体在抵抗病原微生物的防御反应过程中产生的一类具有抗微生物活性的小分子多肽。抗菌肽是机体天然免疫系统的重要组成部分,具有广谱的抗革兰氏阳性、阴性菌活性,对真菌、某些有包膜的病毒、寄生虫以及肿瘤细胞也有抑制活性。抗菌肽具有不同于传统抗生素的独特抗菌机制,病原菌不宜对其产生耐药性,有可能成为一种新的抗生素替代品。介绍了抗菌肽的来源与分类、理化特性与生物学活性,并重点阐述其最新的临床应用进展。     

The innate immune system in the intestine

The innate immune system provides the first line of host defense against invading pathogens. Innate immune responses are initiated by germline-encoded PRR, which recognize specific structures expressed by microorganisms. TLR are a family of PRR which sense a wide range of microorganisms, including bacteria, fungi, protozoa and viruses. TLR are also expressed in the intestine and are critical for intestinal homeostasis. Recently, cytoplasmic PRR, such as NLR and RLR, have been shown to detect pathogens that have invaded the cytosol. One of the NLR, NOD2, is thought to be involved in the pathogenesis of Crohn's disease. This review focuses on the innate immune responses triggered by PRR in the intestine.     

TGF-β in infections and infectious diseases

Since it was first described as having the ability to inhibit macrophage activation, transforming growth factor-beta (TGF-β) has been analyzed for its role in regulating immune responses to a variety of pathogens, including viruses, bacteria, yeast, and protozoa. Most of the studies have involved organisms that infect macrophages, and this discussion will attempt to highlight these findings. Perhaps the most work has been performed with protozoan pathogens, including Trypanosoma cruzi and a variety of Leishmania species, so the discussion will begin with these organisms. Other studies have focused on mycobacteria and viruses, including human immunodeficiency virus, so these areas will also be emphasized in the discussion. For the most part, investigators have reported that TGF-β has, as expected, a negative influence on host responses and a beneficial effect on the survival and growth of intracellular pathogens. However, other studies have found that TGF-β may have a positive or beneficial effect in some models of infection. This review will attempt to highlight studies and conclusions on the roles of TGF-β in infection.     

A Population-Based Acute Meningitis and Encephalitis Syndromes Surveillance in Guangxi,China, May 2007- June 2012

Objectives

Acute meningitis and encephalitis (AME) are common diseases with the main pathogens being viruses and bacteria. As specific treatments are different, it is important to develop clinical prediction rules to distinguish aseptic from bacterial or fungal infection. In this study we evaluated the incidence rates, seasonal variety and the main etiologic agents of AME, and identified factors that could be used to predict the etiologic agents.

Methods

A population-based AME syndrome surveillance system was set up in Guigang City, Guangxi, involving 12 hospitals serving the study communities. All patients meeting the case definition were investigated. Blood and/or cerebrospinal fluid were tested for bacterial pathogens using culture or RT-PCR and serological tests for viruses using enzyme-linked immunosorbent assays. Laboratory testing variables were grouped using factor analysis. Multinomial logistic regression was used to predict the etiology of AME.

Results

From May 2007 to June 2012, the annual incidence rate of AME syndrome, and disease specifically caused by Japanese encephalitis (JE), other viruses, bacteria and fungi were 12.55, 0.58, 4.57, 0.45 and 0.14 per 100,000 population, respectively. The top three identified viral etiologic agents were enterovirus, mumps virus, and JE virus, and for bacteria/fungi were Streptococcus sp., Cryptococcus neoformans and Staphylococcus sp. The incidence of JE and other viruses affected younger populations and peaked from April to August. Alteration of consciousness and leukocytosis were more likely to be caused by JE, bacteria and fungi whereas CSF inflammation was associated with bacterial/fungal infection.

Conclusions

With limited predictive validity of symptoms and signs and routine laboratory tests, specific tests for JE virus, mumps virus and enteroviruses are required to evaluate the immunization impact and plan for further intervention. CSF bacterial culture cannot be omitted in guiding clinical decisions regarding patient treatment.