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Role of veterinary medicine in public health: antibiotic use in food animals and humans and the effect on evolution of antibacterial resistance.

Veterinary public health is another frontier in the fight against human disease. The veterinary public health scope includes the control and eradication of zoonoses, diseases that are naturally transmitted between vertebrate animals and man. These diseases pose a continuous hazard to the health and welfare of the public. More than 100 diseases are categorized as zoonoses, including salmonellosis. It is important to understand how antibiotics are used in humans and in food animals and how these uses affect the evolution of antibacterial resistance. Appropriate use of antibiotics for food animals will preserve the long-term efficacy of existing antibiotics, support animal health and welfare, and limit the risk of transfer of antibiotic resistance to humans. An understanding of the epidemiology of antimicrobial resistance allows development of preventive strategies to limit existing resistance and to avoid emergence of new strains of resistant bacteria. Risk assessments are being used by the Center for Veterinary Medicine at the U.S. Food and Drug Administration as regulatory tools to assess potential risk to humans resulting from antibiotic use in food-producing animals and to then develop microbial safety policies to protect the public health. The veterinary public health scope, in addition to the control and eradication of zoonoses, also includes the development and supervision of food hygiene practices, laboratory and research activities, and education of the public. Thus, it may be seen that there are many ways in which veterinary medicine plays a very important role in public health.

Animals↗

Emerging viral infections.

New microbial threats to human health and survival have arisen intermittently over the centuries. The increasing global population provides greater numbers of hosts for mutational evolution and sufficient hosts to ensure maintenance of new agents; the magnitude and modes of modern travel make a larger population of susceptible people accessible and provide rapid spread of infectious agents. This milieu is particularly hospitable for viruses; therefore, in the future we can anticipate increasing numbers of emerging viral diseases. This article on microbial threats has been limited to viruses associated with neurological diseases.

Animals↗

Views on the sustenance of resistant Mycobacterium tuberculosis in the environment.

Microbial resistance to conventional as well as newly introduced drugs is a hallmark feature of several infectious diseases, notably tuberculosis. It is hypothesized that the greater the selective pressure exerted by increasingly potent drugs, the more rapidly is an organism able to adapt to a drug-containing environment. The roles of drug-containing environments, and the immunological status of the host and bacterial molecular mechanisms of development of drug resistance to Mycobacterium tuberculosis have been examined and examples cited for implementation of modified drug regimens in tuberculosis-control programmes. The views expressed, albeit restricted to Mycobacterium tuberculosis, encourage consideration of drug regimens on a disease evolution basis as well as understanding of the natural rules that govern development and sustenance of drug resistance in the microbial world.

Antitubercular Agents↗

Physiological diversity and niche adaptation in marine Synechococcus.

During the twenty years or so since the discovery of tiny photosynthetic cells of the genus Synechococcus in marine oceanic systems, a tremendous expansion of interest has been seen in the literature pertaining to these organisms. The fact that they are ubiquitous and abundant in major oceanic regimes underlies their ecological importance as significant contributors to marine C fixation. Recent advances in the physiology and biochemistry of these organisms are presented here, focusing on strains of the MC-A and MC-B clusters; it is stressed that the data contained herein should be put into the context of the ecological niche occupied by particular genotypes in situ. This system is ripe for joining the often separate disciplines of molecular ecology and microbial physiology and provides a great opportunity to tease out the underlying processes that both mediate organism evolution and also the environmental factors that dictate this.

Carbon↗

Screening for novel enzymes for biocatalytic processes: accessing the metagenome as a resource of novel functional sequence space.

Historically, biotechnology has missed up to 99% of existing microbial resources by using traditional screening techniques. Strategies of directly cloning 'environmental DNA' comprising the genetic blueprints of entire microbial consortia (the so-called 'metagenome') provide molecular sequence space that along with ingenious in vitro evolution technologies will act synergistically to bring a maximum of available sequence-space into biocatalytic application.

Bacteria↗

Chronic renal failure and periodontal disease.

In order to define the effects of chronic renal failure (CRF) in the progress of gingival inflammation, we studied 6 patients (4 male, 2 female) with CRF who were on chronic hemodialysis for 4.25 (range 1-15) years. Six healthy individuals, age and sex matched were used as controls. The protocol which we used comprised of two periods (a) a 40-day duration period of preparation and (b) a 28-day duration experimental period. During the (a) period, all subjects went through: (1) therapy of the chronic gingivitis and (2) complete control of dental plaque by oral hygiene. During the experimental period, all subjects were advised to avoid, for at least 21 days, any mechanical or chemical media of oral hygiene and went through photographing, recording of gingival index (GI), recording of plaque index (PII), and the collection and quantification of gingival crevicular fluid (GCF). On the 21st day, root planning and polishing were performed and subjects were advised to carry out oral hygiene. On the 28th day, all previous examinations (GI, PII, GCF) were repeated. In both patients and controls, GI, PII and GCF were increased on 7th, 14th and 21st day, without significant differences between the groups and returned to normal (close to zero point) on the 28th day. There are no significant differences between patients with CRF and normal controls in the evolution of experimental gingivitis. Therefore, chronic uremia has no effect on the defense of periodontal tissue against microbial plaque.

Adult↗

Tumour necrosis factor production in fulminant hepatic failure: relation to aetiology and superimposed microbial infection.

Tumour necrosis factor-alpha (TNF-alpha), a cytokine derived from macrophages, is considered to be an important endogenous mediator of endotoxic shock. Patients with fulminant hepatic failure are particularly susceptible to infection and the development of multi-organ failure and similarities to endotoxic shock suggest a possible pathogenetic role for TNF in fulminant hepatic failure. In vitro TNF production was therefore investigated serially in 21 consecutive patients with fulminant hepatic failure and in 21 healthy controls. Spontaneous and lipopolysaccharide-stimulated TNF production were elevated in viral-induced fulminant hepatic failure, compared with healthy controls (P less than 0.05 and P less than 0.01, respectively). By contrast, patients with paracetamol-induced fulminant hepatic failure had normal spontaneous and lipopolysaccharide-stimulated TNF production, while those who died had significantly reduced spontaneous TNF production compared with survivors (P less than 0.02); this difference was present throughout admission. In this group elevations in TNF production above baseline were associated with Gram-positive bacterial or fungal infection but not Gram-negative bacterial infection. There was no correlation between any of the clinical complications of fulminant microbial stimuli in fulminant hepatic failure, but do not support a direct role for TNF in the evolution of the clinical complications of fulminant hepatic failure.

Acetaminophen↗

CD1 antigen presentation and infectious disease.

Taken together, the data generated thus far strongly suggest that CD1 plays a role in the immune response against various infections (table 1). For obvious reasons, the data gathered thus far using model infection systems have focused primarily on the mouse and therefore only examine the role of CD1d. This leaves an important gap in our understanding of the CD1 antigen presentation pathway given the potential role of CD1a, CD1b and CD1c for contributing to antimicrobial immunity. The functional dichotomy between group 1 and group 2 CD1 isoforms obviously requires further analysis. However, we propose that the group 1 CD1 (CD1a, CD1b, CD1c) antigen presentation pathway is closer to the traditional adaptive immune response mechanisms with the capacity to present unique foreign antigens to specific T cells. This broadens the universe antigens that T cells can use to target pathogens and provides important antimicrobial effector mechanisms that may be critical for combating some types of infections. Lipid antigens may also provide a more effective means of targeting intracellular pathogens by T cells since CD1 is able to sample almost all of the intracellular reservoirs that are exploited by this class of pathogen and may provide an important component of the cytotoxic T cell response [80]. On the other hand, the group 2 CD1 protein (CD1d) may be more intermediate in terms of lying functionally between the innate and adaptive immune systems. The activation of CD1d-restricted T cells may, therefore, help bridge the temporal gap between the onset of innate immunity and the purely adaptive responses typified by the MHC-restricted T cells. Hence, the CD1d-restricted [table: see text] T cells are primed for rapid high-level cytokine release. In addition, the interaction of CD1d-restricted T cells with CD1d on DCs can trigger the release of IL-4 and GM-CSF to promote maturation of tissue-resident DC at the site of infection. The maturation of tissue DC would lead to migration of the activated DC to regional lymph nodes and initiation of MHC-restricted T cell responses. Subsequent IL-12 production by the DC in response to CD1d-mediated T cell stimulation could then drive IFN-gamma production by CD1d-restricted T cells and influence the polarization of the T cell response to infection. In addition, early bursts of IFN-gamma by CD1d-restricted T cells could also upregulate antimicrobial activity in macrophages and activate other important effector cells such as NK cells prior to MHC-restricted T cell responses. In the constant struggle between the microbial pathogen and its host, the evolutionary balance almost always favors the microbe. The rapid rate of evolution and adaptation of the microbe accounts for most of this advantage. Hence, it is not surprising that the host immune system has evolved a complex set of pathways, in addition to the MHC, that are able to recognize and target the unique molecular signatures of infectious microorganisms. The lipid antigens presented by CD1 add to this array and thus provide a further layer of immune defense to the host for combating pathogens.

Animals↗

Ecotoxicological testing: small is reliable.

The focus of environmental regulations has changed significantly since the introduction of the bioassay as a standard means of assessing environmental impact. Prominent in this change is an increasing emphasis on protecting the integrity of natural ecosystems, which incorporate community- and system-level properties as well as organismal and population processes. Consequently, support for the use of multispecies testing has widened to include not only ecologists in academia but environmental scientists in the regulatory and industrial sector as well. The reason for this trend is clear: the additional environmental realism gained from tests utilizing communities of organisms allows for greater insight into the potential hazard of chemicals and other forms of human activity to natural ecosystems that cannot be obtained from single species tests alone. Many of the problems cited for multispecies testing early in their evolution as a hazard assessment tool have been refuted or overcome. In particular, the use of natural microbial communities minimizes several shortcomings typically associated with multispecies toxicity testing. This article includes the utility of microcosm and mesocosm tests using aquatic microbial communities as hazard assessment tools in conjunction with accumulating information on their performance in toxicity testing protocols. An increasing body of experimental evidence supports an expansion in the use of these tests for a variety of regulatory and research purposes. A shift in research focus is needed, however, to answer remaining questions and further refine standard protocols for these valuable ecotoxicological tools.

Biological Assay↗

Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae.

Genome rearrangements, especially amplifications and deletions, have regularly been observed as responses to sustained application of the same strong selective pressure in microbial populations growing in continuous culture. We studied eight strains of budding yeast (Saccharomyces cerevisiae) isolated after 100-500 generations of growth in glucose-limited chemostats. Changes in DNA copy number were assessed at single-gene resolution by using DNA microarray-based comparative genomic hybridization. Six of these evolved strains were aneuploid as the result of gross chromosomal rearrangements. Most of the aneuploid regions were the result of translocations, including three instances of a shared breakpoint on chromosome 14 immediately adjacent to CIT1, which encodes the citrate synthase that performs a key regulated step in the tricarboxylic acid cycle. Three strains had amplifications in a region of chromosome 4 that includes the high-affinity hexose transporters; one of these also had the aforementioned chromosome 14 break. Three strains had extensive overlapping deletions of the right arm of chromosome 15. Further analysis showed that each of these genome rearrangements was bounded by transposon-related sequences at the breakpoints. The observation of repeated, independent, but nevertheless very similar, chromosomal rearrangements in response to persistent selection of growing cells parallels the genome rearrangements that characteristically accompany tumor progression.

Aneuploidy↗

The pathologic anatomy of alpha chain disease.

alpha CD is an immunoproliferative disorder which is most frequently, but not always, associated with the disease entity referred to as Mediterranean lymphoma with malabsorption. In most cases, the evolution of the disease and its morbid anatomy suggests an immune deficiency state in which an abnormal clone of intestinal plasma cells incapable of producing the complete IgA molecule proliferates, perhaps in response to microbial antigenic stimulation. In the majority of cases, this proliferation is composed of mature appearing plasma cells which lack morphologic features of malignancy. Although possibly reversible, this proliferation appears to be highly susceptible to the evolution of secondary neoplastic clones, which appear in most instances after a clinical course of unpredictable duration and manifest themselves in the form of single or multiple immunoblastic sarcomas.

Heavy Chain Disease↗

Diversity estimates of microeukaryotes below the chemocline of the anoxic Mariager Fjord, Denmark.

Microbial communities of extreme environments have often been assumed to have low species richness. We analysed 18S rRNA gene signatures in a sample collected below the chemocline of the anoxic Mariager Fjord in Denmark, and from these data we computed novel parametric and standard nonparametric estimates of protistan phylotype richness. Our results indicate unexpectedly high richness in this environment: at the 99.5% phylotype definition, our most conservative estimate was 568 phylotypes (+/-114, standard error). Phylogenetic analyses revealed that the sequences collected cover the majority of described lineages in the eukaryotic domain. Out of 384 sequences analysed, 307 were identified as protistan targets, none of which was identical to known sequences. However, based on what is known about species that are phylogenetically related to the Mariager sequences, most of the latter seem to belong to strictly or facultative anaerobe organisms. We also found signatures that together with other environmental 18S rRNA gene sequences represent environmental clades of possibly high taxonomic levels (class to kingdom level). One of these clades, consisting exclusively of sequences from anoxic sampling sites, branches at the base of the eukaryotic evolutionary tree among the earliest eukaryotic lineages. Assuming eukaryotic evolution under oxygen-depleted conditions, these sequences may represent immediate descendants of early eukaryotic ancestors.

Colony Count, Microbial↗