Pathogens

A pathogen is an organism causing disease to its host. The severity of the diease depends on the pathogens’ virulence. Pathogens are comprised of viruses, bacteria, unicellular and multicellular eukaryotes. There are two classifications of pathogens in Disease Ecology: microparasites and macroparasites. Macroparasites includes helminths, and arthropods; while, microparasites include bacteria, and viruses. However, there are futher classifications of pathogens that are determined by the pathogen’s life cycle. A facultative pathogen is one that does not need the host in order to reproduce - there are typically environmental bacteria and fungi. In contrast, an obligate pathogen needs a host to complete their life cycle.

Question 1

Question

Are viruses classifed as facultative or obligate pathogens? Why

Solution

ALL viruses are an obligate pathogen because they need the host’s cellular machinery in order to reproduce

Microparasites

Bacteria

The majority of bacteria are non-disease causing or nonpathogenic. Less than 1% of bacteria is capable of invading the human body and causing illness (pathogenic). However, when one of these pathogenic bacteria is able to infect its host, a small battle ensues between the host’s immune system and the bacteria. The bacteria are trying to remain present and multiple while the host is trying to prevent the bacteria from gaining access and reproducing. A host becomes infected when there is a persistance or multiplication of the pathogen on or within the host. Once a bacterium has infected the host, it is still in competition with the normal flora to survive. One way bacteria can out compete the normal flora is by producing toxic compounds that are harmful to the host. These compounds can cause vomiting, diarrhea, paralysis, pain, or fever. Bacteria can also enter the host’s cells and cause direct damage to the tissues during replication. The good news is that most illness caused by bacteria can be remedied with an antibiotic.

Antibiotic Resistance in Bacteria

Antibiotics are used for preventing and treating infections caused by specific bacteria, and are critical in combatting life-threatening infections. Bacteria are classified as resistant to antibiotics when they no longer respond to the antibiotics designed to kill them. There are many different ways that a bacterium can become antibiotic-resistance which include random mutation, acquisition of new DNA (usually from another bacterium), and from bacteriophages, which are viruses that infect bacteria.

Question 2

Question

What are some methods suggested by public health officials to protect yourself against antibiotic resistance? You may want to use https://www.cdc.gov/antibiotic-use/index.html as a reference.

Solution

Protect yourself and your family from antibiotic resistance by doing your best to stay healthy and keep others healthy, cleaning hands, covering coughs, staying home when sick, and getting recommended vaccines, such as the flu vaccine. If you get sick, see a doctor! Never pressure them to give antibiotics. If you are prescribed antibiotics take them exactly as the doctor says to, don’t share them, save them for later, take someone else, etc.

Viruses

The term virus was originally used to describe diseases of unknown origin because many epidemics were caused by viruses before anyone understood the nature of viruses themselves. Viruses are not able to reproduce independently and need to hijack the cellular machinery of the host in order to reproduce. An important note is that viruses usually target one organism, however, all organisms (including other microbes) are capable of being infected by viruses. No matter what the host is all viruses have the same basic life cycle. The only difference is that some viruses need to enter a host cell intact, while others disassemle and only the nucleic acid enters the cell. The structure of viruses is all relatively similar: a nucleic acid core surrounded by proteins. Viruses can be transmitted in a variety of ways:

  • Fecal-oral: pathogens in fecal matter of host are passed to the mouth of another host
  • Respiratory: pathogens in respiatory droplets generated through a host coughing, sneezing, or talking, reach a mucosal surface (eyes, nose, or mouth) of another host.
  • Zoonotic: the pathogen is transmitted directly from an animal to humans through air, bites, or saliva. They can also go through an intermediate species (vector) that does not cause the disease just carries it from the animal to the human.
  • Sexual contact: transmitted from one host to another during sexual contact. In the case of viruses, transmission is usually due to a pathogen getting into the partner’s blood stream through tears.
Type.of.Transmission Example
Fecal-oral Poliovirus, rotavirus
Respiratory Influenza virus, measles virus
Zoonotic Rabies virus, cowpox virus
Sexual Contact HIV, HPV

Question 3

Question

Can you think of another example for each type of transmission?

Type.of.Transmission Example Your.Example
Fecal-oral Poliovirus, rotavirus
Respiratory Influenza virus, measles virus
Zoonotic Rabies virus, cowpox virus
Sexual Contact HIV, HPV
Solution

Fecal-oral includes Cholera, E. coli, Hepititis, Giardia, Tape Worms
Respiratory includes Covid, common cold
Zoonotic includes Lyme disease, malaria, anthrax, hantavirus, leptospirosis
Sexual Contact includes syphilis, herpes, hepititis.
This is not a complete list, this has some of the common ones on it. Some diseases can be transmitted through more than one route.

How Viruses Replicate

For DNA viruses replication occurs in the nucleus of the cell. For RNA viruses replication occurs in the cytoplasm. There are six general steps to replication, but the mechanisms vary by virus.

  1. Attachment - receptors of the virus and host cell attach
  2. Entry - virus penetrates the cell wall/membrane
  3. Uncoating - virus releases its nucleic acid from the protein coating
  4. Replication - the virus uses the host cell’s machinery to produce more viral nucleic acids and proteins.
  5. Assembly - viral nucleic acids and proteins are assembled
  6. Release - virus are released from the host cell. Typically destroying the host cell.

How Viruses Cause Disease

There are two categories of infections caused by viruses: acute and persistent. Acute infections remain localized and the signs of disease are short-lived. When the host cell’s are destroyed during the release stage of replication there is accompanying cell and tissue damage. This damage will stimulate the host’s immune system and the viral infection will be remedied in a matter of days to months. Persistent infections will survive within the host without any signs of disease. Some are the result of an acute infection that was not fully eliminated. While other persistent infections are referred to as latent because they have long non-infectious periods between the original disease and subsequent disease (e.g. herpes). A persistent infection can also result in continuous chronic infectious stages following a short disease stage.

Question 4

Question

Find an examples of viral disease that have acute infections, and persistent infections.

Solution

Acute (flu, mumps, measles). Persistent (HIV->AIDS, chicken pox -> shingles)

Virulence

Pathogenicity is the ability of a pathogen to cause disease, given infections; while, virulence is the ability of a pathogen to cause severe disease in those with disease. From the pathogen’s perspective it is important to balance the virulence with the route of tranmission. For example, pathogens transmitted through sexual contact wouldn’t want to be highly virulent because then the host will be too sick to go out and mate and transmit the disease to the partner. Many viruses transmitted through sexual contact are mildly virulent, because of this. The level of virulence can also play a role in when a pathogen can shift to infect a new host species, resulting in outbreaks and epidemics. However, changes in virulence and how they occur and how to predict them are not well understood topics in disease ecology.

Question 5

Question

For the 3 other transmission types (fecal-oral, respiratory, and zoonotic) what level of virulence do you think those pathogens would typically want to have? Why?

Solution

The best for all pathogens is moderate virulence, sick enough to be highly replicating within the host, but not high enough to keep the person inside and away from all that can be transmitted to. Overall, there isn’t a correct answer, this is an exercise to the get the student thinking about virulence and from the perspective of the pathogen instead of the host.

Mutations

RNA viruses are known to use all known mechanisms of genetic variation to ensure survival. This constant variation makes it hard for the host’s immune system to detect them and can make it so a single host has multiple versions of the pathogen at once, overwhleming the immune system. Hallmarks of viral replication are high mutation rates, high yields, and short replication times. This can even make medical interventions, like vaccines, hard to develop because the target pathogen is always changing. A classic example of viral replication is HIV. Where a single infected cell is capable of producing 10,000 new HIV viruses, each having 9,749 bases in their genome.

Question 6

Question

Given that there are 0.0003 mutations/base/round of replication in HIV. What is the average number of mutations in a single replication?

Solution

0.0003 * 9749 = 2.9247 (average number of mutations in a single replication)

Question 7

Question

How many mutations across all replicates come from a single infected cell?

Solution

2.9247 * 10000 = 29,247 mutations

Question 8

Question

Knowing that the mutation rate is 0.0003 mutations/base/round, what percent of the 10,000 new HIV viruses will have at least 1 mutation in the envelope gene that is typically the target for host’s immune system and for vaccines? (the envelope gene is 2,598 bases long)

Solution

0.0003 * 2,598 = 0.7794 proportion of mutations per replicate
0.7794 * 10000 = 7794 replicates will have a mutation in the envelope protein
(7794 / 10000) * 100 = 77.94% of virion produced will have at least 1 mutation in the envelope

Question 9

Question

Seeing the mutation rate of HIV and HIV’s envelope protein, why do you think it has been difficult to create a cure for HIV?

Solution

The mutation rate for the virus is very high, with each replicate have almost 3 mutation, and typically one occuring in the envelope protein that is what the cure (like a vaccine) would target. Each person’s immune system is likely have trouble being able to detect all of the different variants, creating a vaccine that is able to target all of the variants across all people is a huge undertaking.