BACTERIAL PATHOGENESIS

A. AN OVERVIEW OF MICROBIAL PATHOGENESIS

Fundamental Statements for this Learning Object:

1. Only a relatively few bacteria cause human disease.
2. The complex mutually beneficial symbiotic relationship between humans and their natural microbes is critical to good health.
3. An infection is when a microorganism has established itself in a host - has colonized that host - whether not it causing harm or imparting damage.
4. A disease is where there is impairment to host function as a result of damage or injury.
5. Etiology refers to the causes of diseases or pathologies; in terms of infectious disease, the etiologic agent is the microorganism causing that disease.
6. A sign is an objective indication of some medical fact or characteristic that may be detected by a health care professional during a physical examination; a symptom is a condition experienced and reported by the patient.
7.The reservoir of an infectious agent is the habitat in which that microbe normally lives, grows, and multiplies.
8. Transmission of microorganisms by direct contact refers to transfer by such means as skin-to-skin contact, kissing, and sexual intercourse.
9. Transmission of microorganisms by direct droplet contact refers to transfer by aerosols produced by sneezing and coughing.
10. Transmission of microorganisms by indirect contact refers to transfer by suspended air particles, inanimate objects, or vectors (ticks, mosquitoes, fleas).
11. The manner in which a pathogen enters a susceptible host is referred to as its portal of entry; the manner in which it leaves its host is its portal of exit.
12. If relatively few bacteria enter the body then the body's natural defenses against infection have a much better chance of removing them before they can colonize, multiply, and cause harm; if a large number of bacteria enter then the body's defenses may not be as successful.
13. A person with good innate and adaptive immune defenses will be much more successful in removing potentially harmful bacteria than a person that is immunocompromised.
14. Bacterial virulence factors influence a bacterium’s ability to cause infectious disease. These include virulence factors that enable bacteria to colonize the host as well as those that harm or damage the host.

 

LEARNING OBJECTIVES FOR THIS SECTION

1. Infection versus Disease

In this course we are looking at various fundamental concepts of microbiology, with particular emphasis on their relationships to human health. The overall goal is to better understand the total picture of infectious diseases in terms of host-infectious agent interaction.

Bacteria are found in almost every environment. Only a relatively few bacteria cause human disease and many benefit humans. For example, many are important decomposers that assure the flow and recycling of nutrients through ecosystems. Others have important industrial and pharmaceutical uses.

While the typical human body contains an estimated 10 trillion human cells, it also contains over 100 trillion bacteria and other microbes. The complex mutually beneficial symbiotic relationship (def) between humans and their natural microbes is critical to good health. It is now recognized that the millions of genes associated with the normal flora or microbiota (def) of the human body -especially in the intestinal tract - aid in the digestion of many foods, the regulation of multiple host metabolic pathways, and the regulation the body's immune defenses. These collective microbial genes are referred to as the human microbiome (def). There are currently an estimated 3, 000,000 - 5,000,000 genes from over 1000 species that constitute the human microbiome compared to the approximately 23,000 genes that make up the human genome. Some of these same normal microbiota, however, can also cause opportunistic infections (def) when they get into parts of the body where they do not normally live or when the body becomes immunosuppressed.

However, in this section we are going to concentrate on bacteria that are potentially harmful to humans and try to understand what factors influence their ability to cause disease.

Pathogenicity and virulence are terms that refer to an organism's ability to cause disease. Pathogenicity (def) is the ability of a microbe to cause disease and inflict damage upon its host, whereas virulence (def) is the degree of pathogenicity within a group or species of microbes 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, that is its ability to cause disease, is determined by its virulence factors (def).

As learned earlier under Bacterial Genetics, most of the virulence factors that enable bacteria to colonize the body and/or harm the body are the products of quorum sensing genes. Many bacteria use quorum sensing (def) to sense their own population density, communicate with each other by way of secreted chemical factors, and behave as a population rather than as individual bacteria. This plays an important role in pathogenicity and survival for many bacteria.

The genomes of pathogenic bacteria, when compared with those of similar nonpathogenic species or strains, often show extra genes coding for virulence factors (def), that is, molecules expressed and secreted by the bacterium that enable them to colonize the host, evade or inhibit the immune responses of the host, enter into or out of a host cell, and/or obtain nutrition from the host. These include virulence factors such as capsules, adhesins, type 3 secretion systems, invasins, and toxins.

We also learned that most genes coding for virulence factors in bacteria are located in pathogenicity islands or PAIs (def) and are usually acquired by horizontal gene transfer (def). These PAIs may be located in the bacterial chromosome, in plasmids, or even in bacteriophage genomes that have entered the bacterium. The genomes of most pathogenic bacteria typically contain multiple PAIs that can account for up to 10 - 20% of the bacterium's genome. PAIs carry genes such as transpoases (def), integrases (def), or insertion sequences (def) that enable them to insert into host bacterial DNA. Transfer RNA (tRNA) genes are often the target site for integration of PAIs. Conjugative plasmids (def) are the most frequent means of transfer of PAIs from one bacterium to another and the transfer of PAIs can then confer virulence to a previously nonpathogenic bacterium.

An infection (def) is when a microorganism has established itself in a host - has colonized that host - whether not it causing harm or imparting damage. A disease (def), on the other hand, is where there is impairment to host function as a result of damage or injury. For example, the microbes that constitute the body's normal flora or microbiota have infected the body, but they seldom cause disease unless they invade a part of the body where they do not normally reside and/or the host becomes immunocompromised. In medicine, the term etiology refers to the causes of diseases or pathologies. In terms of infectious disease, the etiologic agent (def) is the microorganism causing that disease.

The terms signs and symptoms are often used when diagnosing disease. A sign (def) is an objective indication of some medical fact or characteristic that may be detected by a health care professional during a physical examination. They include such objective indications as blood pressure, respiration, rate, pulse, and temperature. A symptom (def) is a condition experienced and reported by the patient.

2. Causing Infectious Disease

To cause disease, a microorganism must:

a. Maintain a reservoir before and after infection.

The reservoir (def) of an infectious agent is the habitat in which that microbe normally lives, grows, and multiplies. Reservoirs can include humans, animals, and the environment. Many common human infectious diseases have human reservoirs and are transferred person-to-person without intermediaries. Examples include sexually transmitted diseases, measles, most respiratory pathogens, and strep throat. Some infections are transmitted from an animal to a human in which case the infection is called a zoonosis (def). Examples include rabies, plague, and much salmonellosis. Plants, soil, and water in the environment are also reservoirs for some infectious agents such as histoplasmosis, coccidioidomycosis, and Legionnaires disease.

b. Leave the reservoir and gain access to the new host.

The microorganism must leave its reservoir or host through what is called a portal of exit and be transmitted to a new host. For example, the portal of exit for respiratory infections is typically the mouth or nose; for gastrointestinal infections, the feces. Modes of transmission include:

1. Direct contact, as through skin-to-skin contact, kissing, and sexual intercourse. Examples include some Staphylococcus aureus infections, infectious mononucleosis, and gonorrhea.

2. Direct droplet contact, as in the case of aerosols produced by sneezing and coughing. Examples include meningococcal infections and pertussis (whooping cough).

3. Indirect transmission of an infectious agent from a reservoir to a host by suspended air particles, inanimate objects, or vectors.

a. Airborne transmission occurs when infectious agents are carried by dust or droplets suspended in air. Some respiratory infections can be transmitted this way although most are transmitted by contact with infectious mucus.

b. Inanimate objects include water, food, blood, and fomites (inanimate objects such as toys, handkerchiefs, bedding, or clothing). Examples include cholera, salmonellosis, listeriosis, viral hepatitis).

c. Vectors (def) such as ticks, mosquitoes, and fleas. Examples include Lyme's disease, malaria, and typhus fever.

The manner in which a pathogen enters a susceptible host is referred to as its portal of entry. For example, the portal of entry for most respiratory infections is the mouth or nose; for gastrointestinal infections, the mouth. The portal of entry must provide access to tissues with the correct physical and chemical environment (an environment with the proper oxygen content, pH, nutrients, temperature, etc.) in which the pathogen can multiply.

c. Adhere to cells of the skin or mucosa of its new host and colonize the body.

Almost every part of the body has a mechanism for flushing microbes out of or off of the body, including the shedding of epithelial cells from the skin and mucous membranes, urination, defecation, coughing, and sneezing. Unless the microorganisms can replicate fast enough to replace those being flushed out, as in the case of much of the normal microbiota that colonize the lumen of the intestines, they need to adhere to the epithelial cells of the skin and mucous membranes. Also, this body environment must have the correct nutrients, the proper amount of oxygen or lack of oxygen, the right pH, and the right temperature to support the growth of that microorganism. Furthermore, since the body has excellent immune defense mechanisms, anything the microorganism can do to resist body defenses to some degree will also promote colonization.

d. Harm or damage the body.

As stated above, an infection is simply when a microorganism has established itself in a host. To cause disease, that microorganism (or toxin) must inflict damage to the host.

In this unit we are going to take up bacterial pathogenesis. Anything the bacterium does to aid in the requirements needed to cause infectious disease mentioned above will influence its ability to cause disease. Bacteria are able to carry out many of these requirements as a result of their virulence factors. We must keep in mind, however, that whether or not a person actually contracts an infectious disease after exposure to a particular potentially pathogenic bacterium depends not only on the microorganism, but also on the number of bacteria that enter the body and the quality of the person's innate and adaptive immune defenses. (Innate and adaptive immunity will be discussed in detail later in Units 5 and 6.)

For example, if relatively few bacteria enter the body then the body's natural defenses against infection have a much better chance of removing them before they can colonize, multiply, and cause harm. On the other hand, if a large number of bacteria enter then the body's defenses may not be as successful.

Likewise, a person with good innate and adaptive immune defenses will be much more successful in removing potentially harmful bacteria than a person that is immunocompromised. In fact a person highly immunosuppressed, such as a person taking immunosuppressive drugs to suppress transplant rejection, or a person with advancing HIV infection, or a person with other immunosuppressive disorders, becomes very susceptible to infections by microorganisms generally considered not very harmful to a healthy person with normal defenses.

However, in this unit we are going to look at bacterial virulence factors that can influence its ability to cause infectious disease. Virulence factors are molecules expressed and secreted by microorganisms that enable them to colonize the host, evade or inhibit the immune responses of the host, enter into or out of a host cell, and/or obtain nutrition from the host. These virulence factors will be divided into two categories:

A. Virulence factors that promote bacterial colonization of the host.

There are 6 factors we will eventually discuss in this unit that will promote bacterial colonization of humans:

1. The ability to use motility and other means to contact host cells and disseminate within a host.
2. The ability to adhere to host cells and resist physical removal.
3. The ability to invade host cells.
4. The ability to compete for iron and other nutrients.
5. The ability to resist innate immune defenses such as phagocytosis and complement.
6. The ability to evade adaptive immune defenses.

B. Virulence factors that damage or injure the host.

There are 3 factors we will eventually discuss in this unit that can result in harm to humans:

1. The ability to produce pathogen-associated molecular patterns (PAMPS) that bind to host cells causing them to synthesize and secrete inflammatory cytokines and chemokines.
2. The ability to produce harmful exotoxins.
3. The ability to induce autoimmune responses.

- iBiology YouTube Lecture on Microbial Pathogenicity