Surviving Within the Host and Exiting the Host

Intracellular Pathogens

A pathogen or infectious agent is a microorganism such as a virus, bacterium, prion, or fungus that causes disease in its host.

Learning Objectives

Recognize examples of intracellular pathogens

Key Takeaways

Key Points

  • The host may be an animal, a plant, or even another microorganism.
  • Pathogenic viruses are mainly those of the families of Adenoviridae, bacteria Picornaviridae, Herpesviridae, Hepadnaviridae, Flaviviridae, Retroviridae, Orthomyxoviridae, Paramyxoviridae, Papovaviridae, Polyomavirus, Rhabdoviridae, and Togaviridae.
  • Although the vast majority of bacteria are harmless or beneficial, a few pathogenic bacteria can cause infectious diseases.

Key Terms

  • prion: A self-propagating misfolded conformer of a protein that is responsible for a number of diseases that affect the brain and other neural tissue.
  • pathogen: Any organism or substance, especially a microorganism, capable of causing disease, such as bacteria, viruses, protozoa, or fungi. Microorganisms are not considered to be pathogenic until they have reached a population size that is large enough to cause disease.

A pathogen or infectious agent is a microorganism such as a virus, bacterium, prion, or fungus that causes disease in its host. The host may be an animal, a plant, or even another microorganism.

Not all pathogens are undesirable to humans. In entomology, pathogens are one of the “Three P’s” (predators, pathogens, and parasitoids) that serve as natural or introduced biological controls to suppress arthropod pest populations.

There are several types of intracellular pathogens. Pathogenic viruses are mainly those of the families of Adenoviridae, bacteria Picornaviridae, Herpesviridae, Hepadnaviridae, Flaviviridae, Retroviridae, Orthomyxoviridae, Paramyxoviridae, Papovaviridae, Polyomavirus, Rhabdoviridae, and Togaviridae. Viruses typically range between 20 to 300 nanometers in length.

Although the vast majority of bacteria are harmless or beneficial, a few pathogenic bacteria can cause infectious diseases. Bacteria can often be killed by antibiotics because the cell wall in the outside is destroyed, expelling the DNA out of the body of the pathogen, therefore making the pathogen incapable of producing proteins, so it dies. They typically range between 1 and 5 micrometers in length.

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Stanley Prusiner: Stanley Prusiner discovered prions, which are a class of infectious self-reproducing pathogens primarily or solely composed of protein.

Pathogenic fungi comprise a eukaryotic kingdom of microbes that are usually saprophytes but can cause diseases in humans, animals, and plants. Fungi are the most common cause of diseases in crops and other plants. The typical fungal spore size is 1 to 40 micrometers in length.

Some eukaryotic organisms, such as protists and helminths, cause disease. According to the prion theory, prions are infectious pathogens that do not contain nucleic acids. These abnormally-folded proteins are found characteristically in some diseases such as scrapie, bovine spongiform encephalopathy (mad cow disease), and Creutzfeldt–Jakob disease. Although prions fail to meet the requirements laid out by Koch’s postulates, the hypothesis of prions as a new class of pathogen led Stanley B. Prusiner to receive the Nobel Prize in Physiology or Medicine in 1997.

Extracellular Immune Avoidance

A pathogen’s success depends on its ability to evade the host’s immune responses.

Learning Objectives

List the mechanisms that bacteria use for intracellular pathogenesis

Key Takeaways

Key Points

  • Bacteria usually overcome physical barriers by secreting enzymes to digest the barrier in the manner of a type II secretion system.
  • Some pathogens avoid the immune system by hiding within the cells of the host, a process referred to as intracellular pathogenesis.
  • Other pathogens invade the body by changing the non-essential epitopes on their surface rapidly, while keeping the essential epitopes hidden.

Key Terms

  • pathogen: Any organism or substance, especially a microorganism, capable of causing disease, such as bacteria, viruses, protozoa, or fungi. Microorganisms are not considered to be pathogenic until they have reached a population size that is large enough to cause disease.
  • biofilm: A thin film of mucus created by and containing a colony of bacteria and other microorganisms.
  • antigenic variation: The mechanism by which an infectious organism changes its surface proteins in favor of circumventing a host immune response.

Extracellular Immune Avoidance

A pathogen’s success depends on its ability to evade the host’s immune responses. Thus, pathogens have evolved several methods that allow them to successfully infect a host by evading the immune system’s detection and destruction. Bacteria usually overcome physical barriers by secreting enzymes that digest the barrier in the manner of a type II secretion system. They also use a type III secretion system that allows bacteria to insert a hallow tube, which provides proteins a direct route to enter the host cell. These proteins often shutdown the defenses of the host.

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Staphylococcus aureus biofilm: Staphylococcus aureus forming a biofilm on a catheter.

Some pathogens avoid the immune system by hiding within the cells of the host, a process referred to as intracellular pathogenesis. The pathogen hides inside the host cell where it is protected from direct contact with the complement, antibodies, and immune cells. A lot of pathogens release compounds that misdirect or diminish the host’s immune response. Some bacteria even form biofilms which protect them from the proteins and cells of the immune system. Many successful infections often involve biofilms. Some bacteria create surface proteins, such as Streptococcus, that will bind to antibodies making them ineffective.

Other pathogens invade the body by changing the non-essential epitopes on their surface rapidly while keeping the essential epitopes hidden. This is referred to as antigenic variation. HIV rapidly mutates so the proteins that are on its viral envelope, which are essential for its entry into the host’s target cell, are consistently changing. The constant change of these antigens is why vaccines have not been created. Another common strategy that is used is to mask antigens with host molecules in order to evade detection by the immune system. With HIV, the envelope covering the viron is created from the host cell’s outermost membrane making it difficult for the immune system to identify as a non-self structure.

Regulating Virulence

Virulence regulation is a combination of the specific traits of the pathogen and the evolutionary pressures that lead to virulent traits.

Learning Objectives

Compare and contrast the hypotheses that explain why a pathogen evolves as it does: Trade-Off, Short-Sighted Evolution and Coincidental Evolution Hypotheses

Key Takeaways

Key Points

  • Virulence is the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host.
  • The ability of a microorganism to cause disease is described in terms of the number of infecting bacteria, the route of entry into the body, the effects of host defense mechanisms, and intrinsic characteristics of the microorganism called virulence factors.
  • Optimal virulence increases with horizontal transmission (between non-relatives) and decreases with vertical transmission (from parent to child).
  • The pathogen population can evolve once it is in the host.
  • The three main hypotheses about why a pathogen evolves as it does are the Trade-Off Hypothesis, the Short-Sighted Evolution Hypothesis, and the Coincidental Evolution Hypothesis.

Key Terms

  • virulence: The degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host and it is determined by virulence factors.

Virulence is the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism – its ability to cause disease – is determined by its virulence factors. In an ecological context, virulence can be defined as the host’s parasite-induced loss of fitness. Virulence can be understood in terms of proximate causes—those specific traits of the pathogen that help make the host ill—and ultimate causes—the evolutionary pressures that lead to virulent traits occurring in a pathogen strain.

The ability of a microorganism to cause disease is described in terms of the number of infecting bacteria, the route of entry into the body, the effects of host defense mechanisms, and intrinsic characteristics of the microorganism called virulence factors. Host-mediated pathogenesis is often important because the host can respond aggressively to infection with the result that host defense mechanisms do damage to host tissues while the infection is being countered.

According to evolutionary medicine, optimal virulence increases with horizontal transmission (between non-relatives) and decreases with vertical transmission (from parent to child). This is because the fitness of the host is bound to the fitness in vertical transmission but is not so bound in horizontal transmission.The pathogen population can evolve once it is in the host. There are three main hypotheses about why a pathogen evolves as it does. These three models help to explain the life history strategies of parasites, including reproduction, migration within the host, virulence, etc.

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Tuberculosis Culture: The bacteria Mycobacterium tuberculosis can evolve to subvert the protection offered by immune defenses. This close-up reveals this organism’s colonial morphology. Note the colorless rough surface, which are typical morphologic characteristics seen in Mycobacterium tuberculosis colonial growth. Macroscopic examination of colonial growth patterns is still one of the ways microorganisms are often identified.

  1. Trade-off hypothesis argues that pathogens tend to evolve toward ever decreasing virulence because the death of the host (or even serious disability) is ultimately harmful to the pathogen living inside. For example, if the host dies, the pathogen population inside may die out entirely. Therefore, it was believed that less virulent pathogens that allowed the host to move around and interact with other hosts should have greater success reproducing and dispersing. But this is not necessarily the case. Pathogen strains that kill the host can increase in frequency as long as the pathogen can transmit itself to a new host, whether before or after the host dies. The evolution of virulence in pathogens is a balance between the costs and benefits of virulence to the pathogen.
  2. Short-sighted evolution hypothesis suggests that the traits that increase reproduction rate and transmission to a new host will rise to high frequency within the pathogen population. These traits include the ability to reproduce sooner, reproduce faster, reproduce in higher numbers, live longer, survive against antibodies, or survive in parts of the body the pathogen does not normally infiltrate. These traits typically arise due to mutations, which occur more frequently in pathogen populations than in host populations, due to the pathogens’ rapid generation time and immense numbers. After only a few generations, the mutations that enhance rapid reproduction or dispersal will increase in frequency. The same mutations that enhance the reproduction and dispersal of the pathogen also enhance its virulence in the host, causing much harm (disease and death). If the pathogen’s virulence kills the host and interferes with its own transmission to a new host, virulence will be selected against. But as long as transmission continues despite the virulence, virulent pathogens will have the advantage.
  3. Coincidental evolution hypothesis argues that some forms of pathogenic virulence did not co-evolve with the host. For example, tetanus is caused by the soil bacterium Clostridium tetani. After C. tetani bacteria enter a human wound, the bacteria may grow and divide rapidly, even though the human body is not their normal habitat. While dividing, C. tetani produce a neurotoxin that is lethal to humans. But it is selection in the bacterium’s normal life cycle in the soil that leads it to produce this toxin, not any evolution with a human host. The bacterium finds itself inside a human instead of in the soil by mere happenstance. We can say that the neurotoxin is not directed at the human host.

Portals of Exit

Pathogens must have a way to be transmitted from one host to another to ensure their species’ survival.

Learning Objectives

Distinguish between horizontal and vertical disease transmission

Key Takeaways

Key Points

  • Transmission of microorganisms can happen directly from one person to another by: droplet contact, direct physical contact, indirect physical contact, airborne transmission, or fecal-oral transmission.
  • Transmission can also be indirect, via another organism, either a vector or an intermediate host.
  • Disease can also be transmitted in two ways: horizontally from one individual to another in the same generation and vertically from parent to offspring, such as through perinatal transmission.

Key Terms

  • transmission: Transmission is the passing of a communicable disease from an infected host individual or group to a conspecific individual or group, regardless of whether the other individual was previously infected.

Transmission is the passing of a communicable disease from an infected host individual or group to a conspecific individual or group by one or more of the following means: droplet contact, direct physical contact, indirect physical contact, airborne transmission, and fecal-oral transmission.

Transmission can also be indirect, via another organism. Indirect transmission could involve zoonoses or, more typically, larger pathogens like macroparasites with more complex life cycles. Disease can be directly transmitted in two ways. The first is horizontal disease transmission – from one individual to another in the same generation by either direct contact, or indirect contact air, such as via a cough or sneeze. The second is vertical disease transmission – passing a disease causing agent vertically from parent to offspring, such as through perinatal transmission.

Pathogens must have a way to be transmitted from one host to another to ensure their species ‘ survival. Infectious agents are generally specialized for a particular method of transmission. For example, a virus or bacteria that causes its host to develop coughing and sneezing symptoms has a great survival advantage – it is much more likely to be ejected from one host and carried to another. This is also the reason that many microorganisms cause diarrhea.

The respiratory route is a typical mode of transmission among many infectious agents. If an infected person coughs or sneezes on another person, the microorganisms, suspended in warm, moist droplets, may enter the body through the nose, mouth, or eye surfaces. Diseases that are commonly spread by coughing or sneezing include: bacterial meningitis and chickenpox.

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Sneezing: Sneezing can spread disease by launching disease vectors into the air.

When viruses are shed by an infected person through coughing or sneezing into the air, the mucus coating on the virus starts to evaporate. Once this mucus shell evaporates the remaining viron is called a droplet nucleus or quanta. The mucus evaporation rate is determined by the temperature and humidity inside the room. The lower the humidity, the quicker the mucus shell evaporates thus allowing the droplet nuclei to stay airborne and not drop to the ground. The low indoor humidity levels in wintertime buildings ensure that higher levels of droplet nuclei will survive: droplet nuclei are so microscopic that they are able to stay airborne indefinitely on the air currents present within indoor spaces. When an infected person coughs or sneezes, a percentage of their viruses will become droplet nuclei. If these droplet nuclei gain access to the eyes, nose, or mouth of an uninfected person (known as a susceptible) – either directly, or indirectly by touching a contaminated surface – then the droplet nuclei may penetrate into the deep recesses of their lungs. Viral diseases that are commonly spread by coughing or sneezing droplet nuclei include the common cold and influenza.

Direct fecal-oral transmission is rare for humans at least. More common are the indirect routes: foodstuffs or water become contaminated and the people who eat and drink them become infected. This is the typical mode of transmission for infectious agents such as cholera, hepatitis A, and polio.

Sexual transmission refers to any disease that can be caught during sexual activity with another person, including vaginal or anal sex or (less commonly) through oral sex. Transmission is either directly between surfaces in contact during intercourse or from secretions which carry infectious agents that get into the partner’s blood stream through tiny tears in the penis, vagina, or rectum. Some diseases transmissible by the sexual route include: HIV/AIDS and chlamydia.

Sexually transmitted diseases such as HIV and Hepatitis B are thought to not normally be transmitted through mouth-to-mouth contact, although it is possible to transmit some STDs between the genitals and the mouth during oral sex. In the case of HIV this possibility has been established. It is also responsible for the increased incidence of herpes simplex virus 1 (which is usually responsible for oral infections ) in genital infections and the increased incidence of the type 2 virus (more common genitally) in oral infections.

Diseases that can be transmitted by direct contact are called contagious. These diseases can also be transmitted by sharing a towel (where the towel is rubbed vigorously on both bodies) or items of clothing in close contact with the body (socks, for example) if they are not washed thoroughly between uses.