Bacterial vaccines for fish

Vaccination of fish for the prevention of specific bacterial diseases afffecting commercially reared fish species has had a significant impact on this industry. Almost all of the vaccines available at this time are bacterins or formalin-inactivated whole cell suspensions, some with adjuvants. The first vaccines to be successfully commercialized were those against Vibrio anguillarum, Vibrio ordalii, and Yersinia ruckeri in the late 1970s. Developed initially for the salmonid industry, these bacterins are now routinely used worldwide on many species of fish. Though in some areas salmon farming has flourished without the use of these vaccines, in most areas they have been essential to the economic viability of aquaculture operations. Vaccines against Vibrio salmonicida, a pathogen of salmonids, Aeromonas salmonicida, a pathogen of salmonids and carp, and Edwardsiella ictaluri, a pathogen of channel catfish have also been commercialized and are in widespread use. A number of other bacterins have been the subject of research and some of them may eventually be available. Though a bacterin against Vibrio parahaemolyticus, a pathogen affecting species of fish reared in warmwater has been successfully tested, as have bacterins against Aeromonas hydrophila and Edwardsiella tarda, the serologic heterogeneity of these groups of organisms make it unlikely that widely utilizable vaccines will be available in the near future. Those pathogens that appear to be serologically more homogeneous, including Flexibacter columnaris, Pasteurella piscicida and Streptococcus species affecting fish, will likely end up in commercially available bacterins in the not too distant future. The use of a new generation of adjuvants in conjunction with automated injection methods could result in vaccines that will protect against diseases that conventional methods may not be successful against, such as bacterial kidney disease (BKD) caused by Renibacterium salmoninarum.     

Phenotypic and pathobiological characteristics of Pasteurella piscicida

Pasteurellosis, caused by Pasteurella piscicida, is one of the most threatening diseases of wild and cultured marine fish, and has been reported from many geographical areas including the USA, Japan and the Mediterranean countries. The objective of this article is to construct a picture of the current state of knowledge about this bacterial pathogen and the pathogenesis of the disease it causes. We review some important questions such as the controversial taxonomic position of the bacterium, and its main virulence mechanisms. The epidemiology of the disease, the routes of transmission and the putative reservoirs of P. piscicida in the environment are also discussed. Finally, a detailed survey of the strategies for controlling the disease is performed, including new diagnostic procedures, chemotherapy, employment of immunostimulants, and improvements in immunization programs.     

Remodeling of host glycoproteins during bacterial infection

Protein glycosylation is a common post-translational modification found in all living organisms. This modification in bacterial pathogens plays a pivotal role in their infectious processes including pathogenicity, immune evasion, and host-pathogen interactions. Importantly, many key proteins of host immune systems are also glycosylated and bacterial pathogens can notably modulate glycosylation of these host proteins to facilitate pathogenesis through the induction of abnormal host protein activity and abundance. In recent years, interest in studying the regulation of host protein glycosylation caused by bacterial pathogens is increasing to fully understand bacterial pathogenesis. In this review, we focus on how bacterial pathogens regulate remodeling of host glycoproteins during infections to promote the pathogenesis.     

Renibacterium salmoninarum and bacterial kidney disease — the unfinished jigsaw

Bacterial kidney disease (BKD) is one of the most important diseases of wild and cultured salmonid fish, and has been reported from many different countries. Despite considerable effort, many pieces are still missing from the “jigsaw puzzle” which represents our knowledge of the disease, and its etiological agent Renibacterium salmoninarum. The purpose of this review is to consider current knowledge about this bacterial pathogen and the pathogenesis of BKD. It is our intention to construct a picture of the possible ways in which pathogen and host interact, in particular by high-lighting the areas where our understanding is poor and indicating how recent advances in methodology offer the prospect of improvement. The exact status of R. salmoninarum as an obligate fish pathogen, and the implications for transmission, entry, colonization, and disease progression are considered. We review the considerable progress that has been made recently through work on the molecular determinants of pathogenicity, particularly attachment, cellular invasion mechanisms, intracellular survival of the bacterium, and its interactions with the host defense mechanisms and immune system. Finally, we consider ways in which the future control of BKD through improved diagnosis, chemotherapy, and vaccination may be realized through an integrated approach to the study of BKD.     

Edwardsiellosis in fish: a brief review

Edwardsiellosis is one of the most important bacterial diseases in fish. Scientific work on this disease started more than forty years ago and numerous workers around the world are continually adding to the knowledge of the disease. In spite of this, not a single article that reviews the enormous scientific data thus generated is available in the English language. This article briefly discusses some of the recent research on edwardsiellosis, describing the pathogen’s interaction with the host and environment, its pathogenesis and pathology as well as diagnostic, preventive and control measures.     

Edwardsiellosis in fish: a brief review

Edwardsiellosis is one of the most important bacterial diseases in fish. Scientific work on this disease started more than forty years ago and numerous workers around the world are continually adding to the knowledge of the disease. In spite of this, not a single article that reviews the enormous scientific data thus generated is available in the English language. This article briefly discusses some of the recent research on edwardsiellosis, describing the pathogen's interaction with the host and environment, its pathogenesis and pathology as well as diagnostic, preventive and control measures.     

Innate immune responses to Chlamydia pneumoniae infection: role of TLRs,NLRs, and the inflammasome

Chlamydiae are important human pathogens that are responsible for a wide rage of diseases with a significant impact on public health. In this review article we highlight how recent studies have increased our knowledge of Chlamydia pneumoniae pathogenesis and mechanisms of innate immunity directed host defense against C. pneumoniae infection.     

The allometry of host-pathogen interactions

Background

Understanding the mechanisms that control rates of disease progression in humans and other species is an important area of research relevant to epidemiology and to translating studies in small laboratory animals to humans. Body size and metabolic rate influence a great number of biological rates and times. We hypothesize that body size and metabolic rate affect rates of pathogenesis, specifically the times between infection and first symptoms or death.

Methods and Principal Findings

We conducted a literature search to find estimates of the time from infection to first symptoms (t_S) and to death (t_D) for five pathogens infecting a variety of bird and mammal hosts. A broad sampling of diseases (1 bacterial, 1 prion, 3 viruses) indicates that pathogenesis is controlled by the scaling of host metabolism. We find that the time for symptoms to appear is a constant fraction of time to death in all but one disease. Our findings also predict that many population-level attributes of disease dynamics are likely to be expressed as dimensionless quantities that are independent of host body size.

Conclusions and Significance

Our results show that much variability in host pathogenesis can be described by simple power functions consistent with the scaling of host metabolic rate. Assessing how disease progression is controlled by geometric relationships will be important for future research. To our knowledge this is the first study to report the allometric scaling of host/pathogen interactions.     

Host Species and Environmental Effects on Bacterial Communities Associated with Drosophila in the Laboratory and in the Natural Environment

The fruit fly Drosophila is a classic model organism to study adaptation as well as the relationship between genetic variation and phenotypes. Although associated bacterial communities might be important for many aspects of Drosophila biology, knowledge about their diversity, composition, and factors shaping them is limited. We used 454-based sequencing of a variable region of the bacterial 16S ribosomal RNA gene to characterize the bacterial communities associated with wild and laboratory Drosophila isolates. In order to specifically investigate effects of food source and host species on bacterial communities, we analyzed samples from wild Drosophila melanogaster and D. simulans collected from a variety of natural substrates, as well as from adults and larvae of nine laboratory-reared Drosophila species. We find no evidence for host species effects in lab-reared flies; instead, lab of origin and stochastic effects, which could influence studies of Drosophila phenotypes, are pronounced. In contrast, the natural Drosophila–associated microbiota appears to be predominantly shaped by food substrate with an additional but smaller effect of host species identity. We identify a core member of this natural microbiota that belongs to the genus Gluconobacter and is common to all wild-caught flies in this study, but absent from the laboratory. This makes it a strong candidate for being part of what could be a natural D. melanogaster and D. simulans core microbiome. Furthermore, we were able to identify candidate pathogens in natural fly isolates.     

Active Transport of Phosphorylated Carbohydrates Promotes Intestinal Colonization and Transmission of a Bacterial Pathogen

Efficient acquisition of extracellular nutrients is essential for bacterial pathogenesis, however the identities and mechanisms for transport of many of these substrates remain unclear. Here, we investigate the predicted iron-binding transporter AfuABC and its role in bacterial pathogenesis in vivo. By crystallographic, biophysical and in vivo approaches, we show that AfuABC is in fact a cyclic hexose/heptose-phosphate transporter with high selectivity and specificity for a set of ubiquitous metabolites (glucose-6-phosphate, fructose-6-phosphate and sedoheptulose-7-phosphate). AfuABC is conserved across a wide range of bacterial genera, including the enteric pathogens EHEC O157:H7 and its murine-specific relative Citrobacter rodentium, where it lies adjacent to genes implicated in sugar sensing and acquisition. C. rodentium ΔafuA was significantly impaired in an in vivo murine competitive assay as well as its ability to transmit infection from an afflicted to a naïve murine host. Sugar-phosphates were present in normal and infected intestinal mucus and stool samples, indicating that these metabolites are available within the intestinal lumen for enteric bacteria to import during infection. Our study shows that AfuABC-dependent uptake of sugar-phosphates plays a critical role during enteric bacterial infection and uncovers previously unrecognized roles for these metabolites as important contributors to successful pathogenesis.     

Scavenger receptors: role in innate immunity and microbial pathogenesis

Accumulating evidence shows that many scavenger receptors (SR), including SR-A, MARCO and CD36, represent an important part of the innate immune defence by acting as pattern-recognition receptors, in particular against bacterial pathogens. Several SR are expressed on macrophages and dendritic cells, where they act as phagocytic receptors mediating non-opsonic phagocytosis of pathogenic microbes. Another important function of some SR is to act as co-receptors to Toll-like receptors (TLR), modulating the inflammatory response to TLR agonists. On bacteria, the SR ligands have commonly been reported to be lipopolysaccharide and lipoteichoic acid, but recent advances in the field indicate that bacterial surface proteins play a more important role as target molecules for SR than previously thought. Interestingly, recent data show that major pathogens, including Streptococcus pyogenes and the group B streptococcus, have evolved mechanisms to evade SR-mediated recognition. Moreover, intracellular pathogens, such as hepatitis C virus and Plasmodium falciparum, utilize the SR to gain entry into host cells, focusing interest on the importance of SR also in the molecular pathogenesis of infectious diseases. This review highlights the complex interactions between SR and pathogenic microbes, and discusses the role of these interactions in host defence and microbial pathogenesis.     

Bacterial pathogens in wild birds: a review of the frequency and effects of infection

The importance of wild birds as potential vectors of disease has received recent renewed empirical interest, especially regarding human health. Understanding the spread of bacterial pathogens in wild birds may serve as a useful model for examining the spread of other disease organisms, both amongst birds, and from birds to other taxa. Information regarding the normal gastrointestinal bacterial flora is limited for the majority of wild bird species, with the few well-studied examples concentrating on bacteria that are zoonotic and/or relate to avian species of commercial interest. However, most studies are limited by small sample sizes, the frequent absence of longitudinal data, and the constraints of using selective techniques to isolate specific pathogens. The pathogenic genera found in the gut are often those suspected to exist in the birds' habitat, and although correlations are made between bacterial pathogens in the avian gut and those found in their foraging grounds, little is known about the effect of the pathogen on the host, unless the causative organism is lethal. In this review, we provide an overview of the main bacterial pathogens isolated from birds (with particular emphasis on enteropathogenic bacteria) which have the potential to cause disease in both birds and humans, whilst drawing attention to the limitations of traditional detection methods and possible study biases. We consider factors likely to affect the susceptibility of birds to bacterial pathogens, including environmental exposure and heterogeneities within the host population, and present probable avenues of disease transmission amongst birds and from birds to other animal taxa. Our primary aim is to identify gaps in current knowledge and to propose areas for future study.     

Assembly and structure of the T3SS

The Type III Secretion System (T3SS) is a multi-mega Dalton apparatus assembled from more than twenty components and is found in many species of animal and plant bacterial pathogens. The T3SS creates a contiguous channel through the bacterial and host membranes, allowing injection of specialized bacterial effector proteins directly to the host cell. In this review, we discuss our current understanding of T3SS assembly and structure, as well as highlight structurally characterized Salmonella effectors. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.     

Evolutionary genomics of pathogenic bacteria

Complete genome sequences are now available for multiple strains of several bacterial pathogens and comparative analysis of these sequences is providing important insights into the evolution of bacterial virulence. Recently, DNA microarray analysis of many strains of several pathogenic species has contributed to our understanding of bacterial diversity, evolution and pathogenesis. Comparative genomics has shown that pathogens such as Escherichia coli, Helicobacter pylori and Staphylococcus aureus contain extensive variation in gene content whereas Mycobacterium tuberculosis nucleotide divergence is very limited. Overall, these approaches are proving to be a powerful means of exploring bacterial diversity, and are providing an important framework for the analysis of the evolution of pathogenesis and the development of novel antimicrobial agents.     

Tenacibaculosis infection in marine fish caused by Tenacibaculum maritimum: a review

Tenacibaculum maritimum is the aetiological agent of an ulcerative disease known as tenacibaculosis, which affects a large number of marine fish species in the world and is of considerable economic significance to aquaculture producers. Problems associated with epizootics include high mortality rates, increased susceptibility to other pathogens, high labour costs of treatment and enormous expenditures on chemotherapy. In the present article we review current knowledge on this bacterial pathogen, focusing on important aspects such as the phenotypic, serologic and genetic characterization of the bacterium, its geographical distribution and the host species affected. The epizootiology of the disease, the routes of transmission and the putative reservoirs of T. maritimum are also discussed. We include a summary of molecular diagnostic procedures, the current status of prevention and control strategies, the main virulence mechanisms of the pathogen, and we attempt to highlight fruitful areas for continued research.     

Nitric Oxide Releasing Nanoparticles Are Therapeutic for Staphylococcus aureus Abscesses in a Murine Model of Infection

Staphylococcus aureus (SA) is a leading cause of a diverse spectrum of bacterial diseases, including abscesses. Nitric oxide (NO) is a critical component of the natural host defense against pathogens such as SA, but its therapeutic applications have been limited by a lack of effective delivery options. We tested the efficacy of a NO-releasing nanoparticle system (NO-np) in methicillin-resistant SA (MRSA) abscesses in mice. The results show that the NO-np exert antimicrobial activity against MRSA in vitro and in abscesses. Topical or intradermal NO-np treatment of abscesses reduces the involved area and bacterial load while improving skin architecture. Notably, we evaluated pro- and anti-inflammatory cytokines that are involved in immunomodulation and wound healing, revealing that NO-np lead to a reduction in angiogenesis preventing bacterial dissemination from abscesses. These data suggest that NO-np may be useful therapeutics for microbial abscesses.     

The use of mutant and engineered microbial agents for biological control of plant diseases caused by Pythium: Achievements versus challenges

Pythium species are devasting pathogens causing major crop losses, e.g., damping-off in sugar beet caused by Pythium ultimum and root-rot of tomato caused by Pythium aphanidermatum. The use of natural antagonistic microorganisms is a promising environment-friendly approach to control Pythium-caused plant diseases. There are several examples of biocontrol of diseases caused by Pythium species but the application of bioeffectors (biological control agents) is limited for various reasons, including the restricted amount of gene-modification based biotechnological progress. The regulations in many countries prevent genetically modified bioeffectors from being routinely deployed in field conditions. Our two connected aims in this review are (1) to compile and assess achievements in genetic modification of bioeffectors which have been tested for parasitism or antagonism towards a Pythium plant pathogen or biocontrol of a plant disease caused by a Pythium species, and (2) discuss how a better performing bioeffector could be engineered to improve biocontrol of Pythium-caused plant diseases. We focus on the role of seven key mechanisms: cellulases, carbon catabolite de-repression, glycosylation, reactive oxygen species, chitin re-modelling, proteases, and toxic secondary metabolites. Genetic modifications of bioeffectors include gene deletion and overexpression, as well as the replacement of promoter elements to tune the gene expression to the presence of the pathogen. Gene-modifications are limited to fungal and bacterial bioeffectors due to the difficulty of gene modification in oomycete bioeffectors such as Pythium oligandrum. We assess how previous gene modifications could be combined and what other gene modification techniques could be introduced to make improved bioeffectors for Pythium-caused plant diseases. The broad host-range of Pythium spp. suggests engineering improved antagonistic traits of a bioeffector could be more effective than engineering plant-mediated traits i.e., engineer a bioeffector to antagonise a plant pathogen in common with multiple plant hosts rather than prime each unique plant host.