Virulence

11 Key excerpts on "Virulence"

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  eBook - ePub

  Essentials of Disease in Wild Animals

  • Gary A. Wobeser(Author)
  • 2013(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  5

  Damage, Pathogenicity, and Virulence

  The fundamental feature of disease, regardless of cause, is that there is dysfunction that causes harm or cost to the affected animal. The harm may range from effects that are so mild that they are undetectable with most measures that we use commonly (but not necessarily insignificant biologically) to conditions that are acutely lethal to the individual.

  A term is needed that expresses the relative propensity of an agent to injure the animal so that different diseases can be discussed and compared. Two candidate words are in common usage: Virulence and pathogenicity , both of which have been used primarily to describe disease caused by infectious agents. Virulence is derived from Latin virulentus (poisonous) and pathogenesis is derived from Greek pathos (suffering) + genesis (generation or creation), hence, creation of suffering. Virulence is defined in a medical dictionary as “the degree of pathogenicity of a microorganism as indicated by case fatality rates and/or its ability to invade the tissues of the host” (Dorland 2000). Pathogenicity is defined as “the ability of a microorganism to produce disease.” The word “Virulence” also has been used to describe “the ability to cause disease” and virulent as “actively poisonous, intensely noxious, venomous,” suggesting that on an etymological basis, Virulence should be equally applicable to non-infectious and infectious causes of disease.

  Virulence will be used here as a measure of the ability of an agent to cause harm. The degree of injury will not be limited to increased mortality of affected animals. This definition of Virulence is similar to “the harm done to hosts following infection” used by Read et al. (1999). Hochberg and van Baalen (2000) described two types of Virulence that occur in infectious diseases. Type 1 is related to the compatibility of a parasite for a specific host and the evasion or manipulation of the host’s defenses during the sequential stages of infection, development, and transmission from the host. Type 2 deals with the effects of infection on host fitness in terms of increased probability of mortality, reduced levels of reproduction, alterations in host life history, and homeostasis. Only type 2 Virulence will be dealt with here. In human and veterinary medicine, Virulence usually is considered at the level of the individual person or animal. For wild animals, effects on the individual animal are important primarily for their consequences for host life span and fecundity and for how these influence host fitness and population density, so we must consider Virulence in that context. Schall (2002) considered that, from the host animal’s perspective, Virulence is any consequence of infection that reduces the host’s lifetime reproductive success.

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  Molecular Basis of Bacterial Pathogenesis

  • Barbara H. Iglewski(Author)
  • 1990(Publication Date)
  • Academic Press

    (Publisher)

  Part I Introduction This page intentionally left blank THE BACTERIA, VOL. XI CHAPTER 1 The Zen of Bacterial Pathogenicity STANLEY FALKOW Department of Microbiology and Immunology Stanford University Stanford, California 94305 I. Introduction 3 II. The Attributes of Microbial Pathogenicity 4 A. Entry 4 B. Finding a Niche 5 C. Avoiding Host Defense Mechanisms 5 III. Corollaries of Microbial Pathogenicity 6 A. The Clonal Nature of Bacterial Pathogens 6 B. Extrachromosomal Determinants of Pathogenicity 7 C. Regulation of Bacterial Virulence Factors 7 IV. Concluding Remarks 8 I. Introduction A pathogen is often defined as a microorganism that has the capacity to cause disease in a particular host. This definition reflects the past and present emphasis in medical microbiology and medicine with disease, the end product of the infectious process. Not unexpectedly, a good deal of research effort has been, and is, directed to the treatment and prevention of infectious diseases. However, over the past decade there has been an increasing emphasis to understand the funda-mental biology of microorganisms that cause human infection and disease. These studies of infectious bacterial agents have provided a slightly different view of microbial pathogenicity; they also give new insights into the control and preven-tion of infectious diseases. A microbial pathogen is now recognized as a highly adapted microorganism that may cause disease (overt damage to a host) because its survival strategy includes a requirement for infection (persistence, usually by multiplication on or within another living organism). This view, from the standpoint of the micro-organism so to speak, emphasizes the point that disease is an inadvertent and unfavorable outcome of a microbial infection.

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  The Bacteria

  Molecular Basis of Bacterial Pathogenesis

  • Bozzano G Luisa(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  Part I I n t r o d u c t i o n This page intentionally left blank THE BACTERIA, VOL. XI CHAPTER 1 The Zen of Bacterial Pathogenicity STANLEY FALKOW Department of Microbiology and Immunology Stanford University Stanford, California 94305 I. Introduction II. The Attributes of Microbial Pathogenicity 3 4 4 B. Finding a Niche C. Avoiding Host Defense Mechanisms III. Corollaries of Microbial Pathogenicity A. The Clonal Nature of Bacterial Pathogens B. Extrachromosomal Determinants of Pathogenicity C. Regulation of Bacterial Virulence Factors IV. Concluding Remarks I. Introduction A pathogen is often defined as a microorganism that has the capacity to cause disease in a particular host. This definition reflects the past and present emphasis in medical microbiology and medicine with disease, the end product of the infectious process. Not unexpectedly, a good deal of research effort has been, and is, directed to the treatment and prevention of infectious diseases. However, over the past decade there has been an increasing emphasis to understand the funda-mental biology of microorganisms that cause human infection and disease. These studies of infectious bacterial agents have provided a slightly different view of microbial pathogenicity; they also give new insights into the control and preven-tion of infectious diseases. A microbial pathogen is now recognized as a highly adapted microorganism that may cause disease (overt damage to a host) because its survival strategy includes a requirement for infection (persistence, usually by multiplication on or within another living organism). This view, from the standpoint of the micro-organism so to speak, emphasizes the point that disease is an inadvertent and unfavorable outcome of a microbial infection.

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  E-Z Microbiology

  • Barron's Educational Series, Rene Kratz(Authors)
  • 2011(Publication Date)
  • Barrons Educational Services

    (Publisher)

  20

  Pathogenicity ofMicroorganisms

  WHAT YOU WILL LEARN

  This chapter takes a look at the various tools and tricks pathogens use in order to colonize the body and get past your defenses. As you study this chapter, you will: • examine how pathogens enter the body; • discover the importance of attachment; • learn how pathogens evade defenses like complement and phagocytosis; • explore how pathogens damage host tissues with toxins.

  SECTIONS IN THIS CHAPTER

  • Ability to Invade Tissues

  • Evasion of Host Defenses

  • Damage to the Host

  The human body has amazing defenses against invasion by microorganisms. Most microbes we encounter are prevented from establishing an infection by our innate immunity (Chapter 18 ). Those that do establish an infection are usually defeated by our adaptive immunity (Chapter 19 ). So why is it that we get sick at all? How do some microbes manage to get around our defenses? Why does their presence in our bodies cause disease?

  The ability of a microorganism to cause disease is its pathogenicity . A more familiar term might be Virulence , which refers to the degree of pathogenicity. For example, an organism that very easily causes disease would be considered highly virulent. Microorganisms that are highly virulent have the ability to colonize the host easily and disrupt the host physiology. Any molecules that a microorganism makes and that help them to cause disease are called Virulence factors . In other words, Virulence factors are like the tool kit of a pathogen. What makes one pathogen different from another is what they have in their tool kit.

  REMEMBERA Virulence factor is any molecule that helps a pathogen cause disease.

  The ability of a pathogen to cause disease depends on three main issues. First, the pathogen must be able to invade the host. Second, it must be able to evade the host defenses. And finally, it may produce enzymes or toxins that damage host tissues and contribute to the signs and symptoms of disease. The different strategies that pathogens use to invade the human body are truly amazing, and understanding the details of these mechanisms can help us figure out new ways to prevent disease.

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  Safety Assessment of Transgenic Organisms in the Environment, Volume 5

  • OECD(Author)
  • 2016(Publication Date)
  • OECD

    (Publisher)

  The second section of this chapter presented an overview of genes that are involved in different stages of pathogenicity: host recognition and adherence, host invasion, multiplication in the host, the ability to overcome the host immune response and host defense systems, and the ability to damage or kill the host. The perspective of Virulence genes Understanding of bacterial Virulence factors can be biased because of the experimental setup applied to identify or study the factor (Quinn, Newman and King, 1997). For instance, many bacterial toxins are described as “haemolysin”, because they have been originally recognised as cytolytic to erythrocytes. However, in real life these toxins may not be targeted at erythrocytes, but at leukocytes or other host cells instead. This is just one example of how the perception of bacterial Virulence factors is influenced by experimental design. Pathogenicity and Virulence are often addressed in an anthropomorphic manner, i.e. the incorrect concept that it is the “aim” of pathogenic bacteria to cause disease in their host. Like every organism, pathogens have adapted to occupy their ecological niche. Their close association with a host causes damage to their host. Often this damage is “coincidental”, but it may even be beneficial to the survival or spreading of the pathogen. I.1. BACTERIA: PATHOGENICITY FACTORS – 55 SAFETY ASSESSMENT OF TRANSGENIC ORGANISMS: OECD CONSENSUS DOCUMENTS, VOLUME 5 © OECD 2016 Examples are the release of nutrients by cell damage, or enabling contagion of the next host by inducing coughing or diarrhea. The degree of damage is dependent on the equilibrium that results from the interplay of pathogen and host, and may, for instance, be dependent on the immune response of the individual (Casadevall and Pirofski, 1999). Conditions that result in disease can vary among host individuals, and from host species to host species.

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  Respiratory Disease and Infection

  A New Insight

  • Bassam H. Mahboub(Author)
  • 2013(Publication Date)
  • IntechOpen

    (Publisher)

  The results of a viral infection depend on fac‐ tors related to the nature of the virus, the host and the environment. They include: number of infectious particles, the way to reach the target tissue, the rate of multiplication, the effect of virus on cell functions and the host’s immune response. Three requirements must be sat‐ isfied to ensure the infection of an individual host [1]: • Sufficient virus must be available to initiate infection, • Cells at the site of infection must be accessible, susceptible, and permissive for the virus • Local host anti-viral defense systems must be absent or initially ineffective. To infect its host, a virus must first enter cells at a body surface. Common sites of entry in‐ clude the mucosal linings of the respiratory, alimentary and urogenital tracts, the outer sur‐ face of the eye (conjunctival membranes or cornea), and the skin. Among the factors that affect the infection process are: 1. Virus-dependent factors. They usually are dependent on the virus structure. a. Virulence. Virulence is under polygenic control and is not assignable to any isolated property of the virus, but is often associated to characteristics that favor viral repli‐ cation and cellular injury. For example, virulent viruses multiply themselves readily at high temperatures prevailing during the disease, block the synthesis of interferon and macromolecules related to immune system. Viral Virulence is a quantitative statement of the degree or extent of pathogenesis. In general, a virulent virus causes significant disease, whereas an avirulent or attenuated virus causes no or reduced disease, respectively. b. Measuring Viral Virulence. Virulence can be quantified in a number of different ways. One approach is to determine the concentration of virus that causes death or disease in 50% of the infected organisms.

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  Principles of Molecular Virology

  • Carlos Tello Lacal(Author)
  • 2019(Publication Date)
  • Delve Publishing

    (Publisher)

  Such infections are of great significance for they bestow steady immunity to the body of healthy humans (Thomas et al, 1996). Generally, viral pathogenesis is controlled by a number of factors which can be viral or of host origin. The Virulence properties of the infecting virus affect to a great extent the pathogenic mechanism of the virus. The Virulence properties confer to the virus the ability to implantation, replication, and the consequent impairment of the metabolic activities and normal functioning of the target organ. Such properties include the ability of the virus to replicate in various conditions such as in migratory cells, in strong host immunity, during febrile response, and during inflammation. The Virulence properties must also give the virus the ability to overcome the challenges posed by the body in resisting the virus such as the host’s immune system, physical barriers, varied cellular susceptibility to infection, and distance. The virus must also counter the fact that the barriers are specific to both individuals and races. Sometimes unusual natural pressures may make virulent strains occurring in various populations to become dominant. Studies are ongoing to establish the specific genes and proteins that are implicated for the various Virulence properties. Another factor that controls pathogenesis is the accessibility of the body tissues and organs to the virus which is usually hindered by the host’s natural defense mechanisms, the distance the virus has to travel in the body before reaching the target organ, and by physical barriers such as the tissue barriers and the mucus membranes. The host immunity plays an important role as a barrier to pathogenic mechanisms of the virus. If the host cellular surface Pathogenesis 173 characteristics confer vulnerability to it, such as presence of the specific viral receptors, favorable environment for replication and release, then viral pathogenesis will be a success.

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  Parasites in Social Insects

  • Paul Schmid-Hempel(Author)
  • 2019(Publication Date)
  • Princeton University Press

    (Publisher)

  But reduced host fecundity, parasite replication rate within the host, and several other measures have also been used (Bull 1994). Here, the term is used in a broad sense that encompasses these meanings. It will refer to processes that are caused by the parasite and which lead to a re-duction in some component of the host's fitness. More recent discussions, for example, consider the possibility that some of these negative effects are not the result of parasite action but an accidental by-product of the infection (e.g., Levin and Svanborg Eden 1990), or a defense strategy of the host itself (e.g., Williams and Nesse 1991 ). Virulence is associated with a number of processes at various stages of the in-fection. For example, harm could be caused through the penetration of the host body wall, with the depletion of host resources when the parasite feeds, with damage or destruction of host tissue, in the production of toxic substances by the parasite, or by the suppression of the host's immune response. Conse-quently, Virulence should in principle also include instances where the behavior of the host is manipulated by the parasite to increase the probability of its suc-cessful transmission and where it places the individual host at greater risks. Acantocephalan parasites, for example, change the behavior of intermediate hosts, e.g., wood lice, in a way that makes them more likely to be eaten by the final host, a songbird (Moore 1984)(table 3.4). Resistance and Virulence are therefore properties that emerge as a result of host-parasite interaction in a given environment. Their expression is as diverse as the lifestyles and characteristics of hosts and parasites themselves. Also, our knowledge is very far from complete or even satisfactory on most accounts. 7.2 The Biology of Resistance in Insects The very sophisticated immune system of vertebrates is generally not found in insects.

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  Microbiology

  • Nina Parker, Mark Schneegurt, Anh-Hue Thi Tu, Brian M. Forster, Philip Lister(Authors)
  • 2016(Publication Date)
  • Openstax

    (Publisher)

  Highly virulent pathogens will almost always lead to a disease state when introduced to the body, and some may even cause multi-organ and body system failure in healthy individuals. Less virulent pathogens may cause an initial infection, but may not always cause severe illness. Pathogens with low Virulence would more likely result in mild signs and symptoms of disease, such as low-grade fever, headache, or muscle aches. Some individuals might even be asymptomatic. An example of a highly virulent microorganism is Bacillus anthracis, the pathogen responsible for anthrax. B. anthracis can produce different forms of disease, depending on the route of transmission (e.g., cutaneous injection, inhalation, ingestion). The most serious form of anthrax is inhalation anthrax. After B. anthracis spores are inhaled, they germinate. An active infection develops and the bacteria release potent toxins that cause edema (fluid buildup in tissues), hypoxia (a condition preventing oxygen from reaching tissues), and necrosis (cell death and inflammation). Signs and symptoms of inhalation anthrax include high fever, difficulty breathing, vomiting and coughing up blood, and severe chest pains suggestive of a heart attack. With inhalation anthrax, the toxins and bacteria enter the bloodstream, which can lead to multi-organ failure and death of the patient. If a gene (or genes) involved in pathogenesis is inactivated, the bacteria become less virulent or nonpathogenic. Virulence of a pathogen can be quantified using controlled experiments with laboratory animals. Two important indicators of Virulence are the median infectious dose (ID 50 ) and the median lethal dose (LD 50 ), both of which are typically determined experimentally using animal models. The ID 50 is the number of pathogen cells or virions required to cause active infection in 50% of inoculated animals. The LD 50 is the number of pathogenic cells, virions, or amount of toxin required to kill 50% of infected animals.

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  Visualizing Microbiology

  • Rodney P. Anderson, Linda Young, Kim R. Finer(Authors)
  • 2020(Publication Date)
  • Wiley

    (Publisher)

  Describe the host factors that influence the outcome of infection. 2. Describe the microbial factors that influence the outcome of infection. Transmission of a pathogenic microbe to a human host is not all that is required for a microbe to cause disease. Both host factors and microbial factors influence whether an infection results in disease. The pathogenicity of the microbe is deter- mined by the interaction between a myriad of both host and microbial factors (Figure 16.11). Pathogenicity in itself is not a measure of disease severity. Which factors are primarily responsible for determining disease outcome depends on the specific circumstance of the exposure. pathogenicity The ability of a pathogen to cause disease in its host. Health Pathogen factors Host factors Disease Host genetic factors Host genetic factors Innate immune defenses Barriers Physical Chemical Fever Inflammation Phagocytosis Adaptive immune defenses Cell-mediated immune responses Antibody- mediated immune responses Health status Stress Immune status Age Prior immunity Vaccination Previous pathogen exposure Number of microbes needed to cause disease Virulence factors Enzymes Toxins Capsules Biofilm Endospores Fimbriae Portals of entry Skin Mucus membranes Parenteral route Microbial genetic factors Plasmids Mutation Recombination Gene exchange Pathogen type Primary Opportunistic FIGURE 16.11 Host and microbial factors influencing disease outcomes The most important host factors in preventing disease are prior immunity and excellent health. Pathogenicity is largely determined by whether a microbe is a primary pathogen, what its Virulence factors are, and the number of microbes needed to cause disease. Think Critically Which host factor(s) can you most control to help reduce your risk of acquiring an infectious disease? 428 CHAPTER 16 Microbial Pathogenesis Host Factors Not all hosts are susceptible to every specific pathogen because they may have prior immunity to the infectious agent.

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  Microbiology

  • Dave Wessner, Christine Dupont, Trevor Charles, Josh Neufeld(Authors)
  • 2020(Publication Date)
  • Wiley

    (Publisher)

  Gal-Mor, O., and B. B. Finlay. 2006. Pathogenicity islands: A molecu- lar toolbox for bacterial Virulence. Cell Microbiol 8:1707–1719. Raskin, D. M., R. Seshadri, S. U. Pukatzki, and J. J. Mekalanos. 2006. Bacterial genomics and pathogen evolution. Cell 124:703–714. Rossetto, O., M. Pirazzini, and C. Montecucco. 2014. Botulism neuro- toxins: Genetic, structural and mechanistic insights. Nat Rev Micro- biol 12:535–549. Rutherford, S. T., and B. L. Bassler. 2012. Bacterial quorum sensing: Its role in Virulence and possibilities for its control. Cold Spring Harb Perspect Med 2:a012427. Travis, J. 2003. All the world’s a phage: Viruses that eat bacteria abound—and surprise. Sci News 164:26–27. Zughaier, S. M., and P. Cornelis. 2018. Editorial: Role of iron in bac- terial pathogenesis. Front Cell Infect Microbiol 8:334. doi: 10.3389/ fcimb.2018.00344. 9. Production of antibody has not been found to be protective against Mycobacterium tuberculosis infection. Explain why this would be. 10. You encounter what appears to be a newly emerged strain of bac- teria. As you examine its DNA sequence, you determine it has genes for a type III secretion system. What would this sequence analysis tell you about the pathogenesis of these bacteria? 11. Enterotoxigenic strains of E. coli can cause diarrhea in travelers to regions where these strains exist as common gut inhabitants in local populations, yet they do not usually cause disease in local popu- lations. Suggest why these strains are a problem for travelers but not for the locals. 12. If you could design your vision of the ideal pathogenic bacterium that was able to gain access to a host, avoid immune destruction, and obtain nutrients, what Virulence factor genes would you insert in its genome? Explain your reasoning for each. 782 We probably have all heard about “introduced species.” The term refers to species that are released into a non‐native envi- ronment.

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