The ruminal epithelium has an enormous capacity for the absorption of short-chain fatty acids (SCFAs). This not only delivers metabolic energy to the animal but is also an essential regulatory mechanism that stabilizes the intraruminal milieu. The epithelium itself, however, is endangered by the influx of SCFAs because the intracellular pH (pHi) may drop to a lethal level. To prevent severe cytosolic acidosis, the ruminal epithelium is able to extrude (or buffer) protons by various mechanisms: (i) a Na+/H+ exchanger, (ii) a bicarbonate importing system and (iii) an H+/monocarboxylate cotransporter (MCT). Besides pHi regulation, the MCT also provides the animal with ketone bodies derived from the intraepithelial breakdown of SCFAs. Ketone bodies, in turn, can serve as an energy source for extrahepatic tissues. In addition to SCFA uptake, glucose absorption has recently been identified as a potential way of eliminating acidogenic substrates from the rumen. At least with respect to SCFAs, absorption rates can be elevated when adapting animals to energy-rich diets. Although they are very effective under physiological conditions, the absorptive and regulatory mechanisms of the ruminal epithelium also have their limits. An increased number of protons during the state of ruminal acidosis can be eliminated neither from the lumen nor the cytosol, thus worsening dysfermentation and finally leading to functional and morphological alterations of the epithelial lining.

Since its recognition as a human pathogen in the early 1970s, Campylobacter jejuni has now emerged as the leading bacterial cause of food-borne gastroenteritis in developed countries. Poultry, particularly chickens, account for the majority of human infections caused by Campylobacter. Reduction or elimination of this pathogen in the poultry reservoir is an essential step in minimizing the public health problem; however, farm-based intervention measures are still not available because of the lack of understanding of the ecological aspects of C. jejuni on poultry farms. Although Campylobacter is highly prevalent in poultry production systems, how poultry flocks become infected with this organism is still unknown. Many investigations indicate that horizontal transmission from environmental sources is the primary route of flock infections by Campylobacter. However, some recent studies also suggest the possibility of vertical transmission from breeder to progeny flocks. The transmission of the organism is not well understood, but it is likely to be through both vertical and horizontal transmission and may be affected by the immune status of the poultry host and the environmental conditions in the production system. Intervention strategies for Campylobacter infection in poultry should consider the complex nature of its transmission and may require the use of multiple approaches that target different segments of the poultry production system.

Mycoplasma bovis is an important and emerging cause of respiratory disease and arthritis in feedlot cattle and young dairy and veal calves, and has a variety of other disease manifestations in cattle. M. bovis is certainly capable of causing acute respiratory disease in cattle, yet the attributable fraction has been difficult to estimate. In contrast, M. bovis is more accepted as a cause of chronic bronchopneumonia with caseous and perhaps coagulative necrosis, characterized by persistent infection that seems poorly responsive to many antibiotics. An understanding of the disease has been recently advanced by comparisons of natural and experimentally induced disease, development of molecular diagnostic tools, and understanding some aspects of virulence, yet uncertainties regarding protective immunity, the importance of genotypic diversity, mechanisms of virulence, and the role of co-pathogens have restricted our understanding of pathogenesis and our ability to effectively control the disease. This review critically considers the relationship between M. bovis infection and the various manifestations of the bovine respiratory disease complex, and addresses the pathogenesis, clinical and pathologic sequelae, laboratory diagnosis and control of disease resulting from M. bovis infection in the bovine respiratory tract.

Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating viral disease affecting the swine industry worldwide. The etiological agent, PRRS virus (PRRSV), possesses a RNA viral genome with nine open reading frames (ORFs). The ORF1a and ORF1b replicase-associated genes encode the polyproteins pp1a and pp1ab, respectively. The pp1a is processed in nine non-structural proteins (nsps): nsp1α, nsp1β, and nsp2 to nsp8. Proteolytic cleavage of pp1ab generates products nsp9 to nsp12. The proteolytic pp1a cleavage products process and cleave pp1a and pp1ab into nsp products. The nsp9 to nsp12 are involved in virus genome transcription and replication. The 3′ end of the viral genome encodes four minor and three major structural proteins. The GP2a, GP3 and GP4 (encoded by ORF2a, 3 and 4), are glycosylated membrane associated minor structural proteins. The fourth minor structural protein, the E protein (encoded by ORF2b), is an unglycosylated membrane associated protein. The viral envelope contains two major structural proteins: a glycosylated major envelope protein GP5 (encoded by ORF5) and an unglycosylated membrane M protein (encoded by ORF6). The third major structural protein is the nucleocapsid N protein (encoded by ORF7). All PRRSV non-structural and structural proteins are essential for virus replication, and PRRSV infectivity is relatively intolerant to subtle changes within the structural proteins. PRRSV virulence is multigenic and resides in both the non-structural and structural viral proteins. This review discusses the molecular characteristics, biological and immunological functions of the PRRSV structural and nsps and their involvement in the virus pathogenesis.

Bovine herpes virus 1 (BHV-1) is primarily associated with clinical syndromes such as rhinotracheitis, pustular vulvovaginitis and balanoposthitis, abortion, infertility, conjunctivitis and encephalitis in bovine species. The main sources of infection are the nasal exudates and the respiratory droplets, genital secretions, semen, fetal fluids and tissues. The BHV-1 virus can become latent following a primary infection with a field isolate or vaccination with an attenuated strain. The viral genomic DNA has been demonstrated in the sensory ganglia of the trigeminal nerve in infectious bovine rhinotracheitis (IBR) and in sacral spinal ganglia in pustular vulvovaginitis and balanoposthitis cases. BHV-1 infections can be diagnosed by detection of virus or virus components and antibody by serological tests or by detection of genomic DNA by polymerase chain reaction (PCR), nucleic acid hybridization and sequencing. Inactivated vaccines and modified live virus vaccines are used for prevention of BHV-1 infections in cattle; subunit vaccines and marker vaccines are under investigation.

Antibiotics are one of the most important medical discoveries of the 20th century and will remain an essential tool for treating animal and human diseases in the 21st century. However, antibiotic resistance among bacterial pathogens and concerns over their extensive use in food animals has garnered global interest in limiting antibiotic use in animal agriculture. Yet, limiting the availability of medical interventions to prevent and control animal diseases on the farm will directly impact global food security and safety as well as animal and human health. Insufficient attention has been given to the scientific breakthroughs and novel technologies that provide alternatives to antibiotics. The objectives of the symposium ‘Alternatives to Antibiotics’ were to highlight promising research results and novel technologies that could potentially lead to alternatives to conventional antibiotics, and assess challenges associated with their commercialization, and provide actionable strategies to support development of alternative antimicrobials. The symposium focused on the latest scientific breakthroughs and technologies that could provide new options and alternative strategies for preventing and treating diseases of animals. Some of these new technologies have direct applications as medical interventions for human health, but the focus of the symposium was animal production, animal health and food safety during food-animal production. Five subject areas were explored in detail through scientific presentations and expert panel discussions, including: (1) alternatives to antibiotics, lessons from nature; (2) immune modulation approaches to enhance disease resistance and to treat animal diseases; (3) gut microbiome and immune development, health and diseases; (4) alternatives to antibiotics for animal production; and (5) regulatory pathways to enable the licensure of alternatives to antibiotics.

This paper reviews the present state of antimicrobial resistance (AMR) in the zoonotic bacteria Salmonella, Campylobacter jejuni and Campylobacter coli, and in Escherichia coli from chickens and turkeys. For Salmonella, the frequencies and patterns of AMR vary depending on time, region, serovar, the particular farm, layers versus broilers, and the antimicrobial agent. There is usually a higher frequency of AMR in Salmonella from turkeys compared with Salmonella from chickens. Clonal and horizontal transmission of AMR occur and there is concern about the spread of transmissible plasmids that encode extended spectrum cephalosporinases. Resistance to fluoroquinolones is generally low. For Campylobacter, resistance to tetracycline is usually at moderate to high frequency, resistance to quinolones/fluoroquinolones varies from low to high, and resistance to macrolides is usually low. There are high levels of fluoroquinolone resistance in some countries. Avian pathogenic E. coli are often highly resistant, especially to tetracycline, streptomycin, and sulfonamides. Plasmid-mediated resistance is common. High levels of resistance to ciprofloxacin have been reported from China. Commensal E. coli from poultry have similar patterns of resistance but at lower frequencies. Integron associated resistance occurs commonly in Salmonella and E. coli but has not been detected in Campylobacter.

Bovine respiratory disease (BRD) research has provided significant understanding of the disease over the past 26 years. Modern research tools that have been used include monoclonal antibodies, genomics, polymerase chain reaction, immunohistochemistry (IHC), DNA vaccines and viral vectors coding for immunogens. Emerging/reemerging viruses and new antigenic strains of viruses and bacteria have been identified. Methods of detection and the role for cattle persistently infected bovine viral diarrhea virus (BVDV) were identified; viral subunits, cellular components and bacterial products have been characterized. Product advances have included vaccines for bovine respiratory syncytial virus, Mannheimia haemolytica and Pasteurella multocida; the addition of BVDV2 to the existing vaccines and new antibiotics. The role of Mycoplasma spp., particularly Mycoplasma bovis in BRD, has been more extensively studied. Bovine immunology research has provided more specific information on immune responses, T cell subsets and cytokines. The molecular and genetic basis for viral–bacterial synergy in BRD has been described. Attempts have been made to document how prevention of BRD by proper vaccination and management prior to exposure to infectious agents can minimize disease and serve as economic incentives for certified health programs.

New concepts have emerged in the past few years that help us to better understand the emergence and spread of antimicrobial resistance (AMR). These include, among others, the discovery of the mutator state and the concept of mutant selection window for resistances emerging primarily through mutations in existing genes. Our understanding of horizontal gene transfer has also evolved significantly in the past few years, and important new mechanisms of AMR transfer have been discovered, including, among others, integrative conjugative elements and ISCR (insertion sequences with common regions) elements. Simultaneously, large-scale studies have helped us to start comprehending the immense and yet untapped reservoir of both AMR genes and mobile genetic elements present in the environment. Finally, new PCR- and DNA sequencing-based techniques are being developed that will allow us to better understand the epidemiology of classical vectors of AMR genes, such as plasmids, and to monitor them in a more global and systematic way.

Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne’s disease, a deadly intestinal ailment of ruminants. Johne’s disease is of tremendous economic importance to the worldwide dairy industry, causing major losses due to reduced production and early culling of animals. A highly controversial but developing link between exposure to M. paratuberculosis and human Crohn’s disease in some individuals has led to the suggestion that M. paratuberculosis is also a potential food safety concern. As with many other mycobacteria, M. paratuberculosis is exquisitely adapted to survival in the host, despite aggressive immune reactions to these organisms. One hallmark of mycobacteria, including M. paratuberculosis, is their propensity to infect macrophages. Inside the macrophage, M. paratuberculosisinterferes with the maturation of the phagosome by an unknown mechanism, thereby evading the host’s normal first line of defense against bacterial pathogens. The host immune system begins a series of attacks against M. paratuberculosis-infected macrophages, including the rapid deployment of activated γδ T cells, CD4+T cells and cytolytic CD8+ T cells. These cells interact with the persistently infected macrophage and with each other through a complex network of cytokines and receptors. Despite these aggressive efforts to clear the infection, M. paratuberculosis persists and the constant struggle of the immune system leads to pronounced damage to the intestinal epithelial cells. Enhancing our ability to control this important and tenacious pathogen will require a deeper understanding of how M. paratuberculosis interferes with macrophage action, the cell types involved in the immune response, the cytokines these cells use to communicate, and the host genetic factors that control the response to infection.

The successful use of virulent (lytic) bacteriophages (phages) in preventing and treating neonatal enterotoxigenic Escherichia coli infections in calves, lambs and pigs has prompted investigation of other applications of phage therapy in food animals. While results have been very variable, some indicate that phage therapy is potentially useful in virulent Salmonella and E. coli infections in chickens, calves and pigs, and in control of the food-borne pathogens Salmonella and Campylobacter jejuni in chickens and E. coli O157:H7 in cattle. However, more rigorous and comprehensive research is required to determine the true potential of phage therapy. Particular challenges include the selection and characterization of phages, practical modes of administration, and development of formulations that maintain the viability of phages for administration. Also, meaningful evaluation of phage therapy will require animal studies that closely represent the intended use, and will include thorough investigation of the emergence and characteristics of phage resistant bacteria. As well, effective use will require understanding the ecology and dynamics of the endemic and therapeutic phages and their interactions with target bacteria in the farm environment. In the event that the potential of phage therapy is realized, adoption will depend on its efficacy and complementarity relative to other interventions. Another potential challenge will be regulatory approval.

The transport of nitrogen across the rumen epithelium is characterized by absorption of ammonia from the rumen and by an influx of urea into the rumen. The transport rates of both compounds are large and exhibit wide variation. The transport of ammonia occurs in two forms: in the lipophilic form as NH3, the magnitude of which is linearly related to the pH in the ruminal fluid at pH values above 7, while at a physiological pH of 6.5 or lower, ammonia is predominantly absorbed as NH4+ via putative potassium channels in the apical membrane. The uptake of NH4+ depends on the potential difference of the apical membrane, Pda, and shows competition with K uptake. The pathway for basolateral exit of NH4+ is unknown. Hence, the relative transport rates of NH3 or NH4+ are determined by the ruminal pH according to the Henderson–Hasselbalch equation. Transport of ammonia interacts with the transport of Na and Mg mainly via changes of the intracellular pH. Urea recycling into the rumen has been known for many years and the transport across the rumen epithelium is mediated via urea transporters in the luminal and basolateral membrane of the epithelium. Transport of urea occurs by simple diffusion, but is highly variable. A significant increase of urea influx is caused by the fermentation products CO2 and short-chain fatty acids. Conversely, there is some evidence of inhibition of urea influx by ruminal ammonia. The underlying mechanisms of this modulation of urea transport are unknown, but of considerable nutritional importance, and future research should be directed to this aspect of ruminal transport.

Large amounts of antimicrobial agents are still being used in modern swine production in many countries around the world. This facilitates the emergence and development of antimicrobial resistance. Bacteria causing infections in swine have in several cases acquired resistance to a number of the agents most commonly used for treatment, making it difficult to predict the efficacy of different antimicrobial agents without prior susceptibility testing. This review gives an overview of recent susceptibility data from different parts of the world and discusses the importance of the development of resistance not only in the treatment of infections in swine but also taking into account the human health implications of antimicrobial resistance.

The pathogenic strains of Escherichia coli recovered from the intestinal tract of animals fall into categories called enterotoxigenic, enteropathogenic, enterohemorrhagic and necrotoxigenic. The other two categories, enteroinvasive and enteroaggregative, have not been reported in animals. The pathogenicity of these strains is determined by the presence of certain genes that encode adhesins and toxins, are generally organized in large blocks in chromosomes, large plasmids or phages, and are often transmitted horizontally between strains. In this review, we summarize current knowledge of the virulence attributes that determine the pathogenic potential of E. coli strains and the methods available to assess the virulence of the strains. We also discuss the clinical symptoms, the gross and histological lesions, and the molecular diagnostic methods our laboratories have implemented for detecting pathogenic strains of E. coli that are isolated from the gastrointestinal tract of animals.

The purpose of this review was to discuss the history of the development and implementation of oral fluid diagnostics for infectious diseases of humans and domestic animals. The use of oral fluid for the assessment of health and diagnosis of disease in humans and animals has a surprisingly long history. As early as 1909, Pollaci and Ceraulo reported sensitive and specific agglutination of ‘Micrococcus melitensis’ (Brucella melitensis) by oral fluid from patients diagnosed with Malta Fever. A 1986 report of the detection of antibodies against human immunodeficiency virus (HIV) in oral fluid from patients with acquired immunodeficiency syndrome (AIDS) marked the start of a remarkably rapid series of developments in oral fluid-based assays. Cumulatively, the literature strongly supports implementation of oral fluid-based diagnostics in veterinary diagnostic medicine. Pathogen-specific IgA, IgM and IgG antibodies have all been demonstrated in oral fluid collected from diverse domestic animal species in response to infection. A variety of infectious agents, both local and systemic, are shed in oral fluid, including some of the most economically significant pathogens of production animals (e.g. foot-and-mouth disease virus, classical swine fever virus and porcine reproductive and respiratory syndrome virus) Ultimately, point-of-care rapid assays (i.e. cow-side, sow-side or pen-side tests) and access to real-time infectious disease data will revolutionize our delivery of health management services.

The poultry industry faces challenge amidst global food security crisis. Infectious bronchitis is one of the most important viral infections that cause huge economic loss to the poultry industry worldwide. The causative agent, infectious bronchitis virus (IBV) is an RNA virus with great ability for mutation and recombination; thus, capable of generating new virus strains that are difficult to control. There are many IBV strains found worldwide, including the Massachusetts, 4/91, D274, and QX-like strains that can be grouped under the classic or variant serotypes. Currently, information on the epidemiology, strain diversity, and global distribution of IBV has not been comprehensively reported. This review is an update of current knowledge on the distribution, genetic relationship, and diversity of the IBV strains found worldwide.

Actinobacillus pleuropneumoniae is an important pig pathogen that is responsible for swine pleuropneumonia, a highly contagious respiratory infection. Knowledge of the importance, composition and structural determination of the major antigens involved in virulence provides crucial information that could lead to the development of a rationale for the production of specific serodiagnostic tools as well as vaccine development. Thus, efforts have been devoted to study mainly A. pleuropneumoniaevirulence determinants with special emphasis on the Apx toxins (for A. pleuropneumoniaeRTX toxins). In comparison, little attention has been given to the surface polysaccharides, which include capsular polysaccharides (CPS) and cell-wall lipopolysaccharides (LPS). Here, we review current knowledge on CPS and LPS of A. pleuropneumoniae used as diagnostic tools to monitor the infection and as immunogens for inclusion in vaccine preparations for animal protection.

Streptococcus suis is an invasive porcine pathogen associated with meningitis, arthritis, bronchopneumonia and other diseases. The pathogen constitutes a major health problem in the swine industry worldwide. Furthermore, S. suis is an important zoonotic agent causing meningitis and other diseases in humans exposed to pigs or pork. Current knowledge on pathogenesis is limited, despite the enormous amount of data generated by ‘omics’ research. Accordingly, immunprophylaxis (in pigs) is hampered by lack of a cross-protective vaccine against virulent strains of this diverse species. This review focuses on bacterial factors, both surface-associated and secreted ones, which are considered to contribute to S. suis interaction(s) with host factors and cells. Factors are presented with respect to (i) their identification and features, (ii) their distribution among S. suis and (iii) their significance for virulence, immune response and vaccination. This review also shows the enormous progress made in research on S. suis over the last few years, and it emphasizes the numerous challenging questions remaining to be answered in the future.

West Nile virus (WNV) is a flavivirus that is maintained in a bird–mosquito transmission cycle. Humans, horses and other non-avian vertebrates are usually incidental hosts, but evidence is accumulating that this might not always be the case. Historically, WNV has been associated with asymptomatic infections and sporadic disease outbreaks in humans and horses in Africa, Europe, Asia and Australia. However, since 1994, the virus has caused frequent outbreaks of severe neuroinvasive disease in humans and horses in Europe and the Mediterranean Basin. In 1999, WNV underwent a dramatic expansion of its geographic range, and was reported for the first time in the Western Hemisphere during an outbreak of human and equine encephalitis in New York City. The outbreak was accompanied by extensive and unprecedented avian mortality. Since then, WNV has dispersed across the Western Hemisphere and is now found throughout the USA, Canada, Mexico and the Caribbean, and parts of Central and South America. WNV has been responsible for >27,000 human cases, >25,000 equine cases and hundreds of thousands of avian deaths in the USA but, surprisingly, there have been only sparse reports of WNV disease in vertebrates in the Caribbean and Latin America. This review summarizes our current understanding of WNV with particular emphasis on its transmission dynamics and changing epidemiology.

The intestinal mucosa represents the most active defense barrier against the continuous challenge of food antigens and pathogenic microorganisms present in the intestinal lumen. Protection against harmful agents is conferred by factors such as gastric acid, peristalsis, mucus, intestinal proteolysis, and the intestinal biota. The establishment of beneficial bacterial communities and metabolites from these complex ecosystems has varying consequences for host health. This hypothesis has led to the introduction of novel therapeutic interventions based on the consumption of beneficial bacterial cultures. Mechanisms by which probiotic bacteria affect the microecology of the gastrointestinal tract are not well understood, but at least three mechanisms of action have been proposed: production/presence of antibacterial substances (e.g., bacteriocins or colicins), modulation of immune responses and specific competition for adhesion receptors to intestinal epithelium. The rapid establishment of bacterial communities has been thought to be essential for the prevention of colonization by pathogenic bacteria. Some animal models suggest that the reduction in bacterial translocation in neonatal animals could be associated with an increase in intestinal bacterial communities and bacteriocin-like inhibitory substances produced by these species. This review emphasizes the role of the intestinal microbiota in the reduction of the gastrointestinal infections and draws heavily on studies in poultry.