Chapter 15: Microbial Mechanisms of Pathogenicity

Pathology

study of the cause of disease

Etiology

study of disease

Pathogenesis

multiplication of any parasitic organisms

Infection

development of disease

disease

Disturbance in the state of health where
the body can’t carry out all of its normal
functions

Signs of disease

• Objective and measurable

• Directly observed by a clinician

• Changes in any vital signs may be indicative of disease

Symptoms of Disease

• Subjective

• Felt or experienced by a patient but cannot be confirmed or measured.

• Changes in any vital signs may be indicative of disease

Syndrome

A specific group of signs and symptoms

Infectious disease

caused by infectious agents

Noninfectious disease

caused by some other factor - for example a poison

Communicable or contagious diseases

Can be spread from host to host - measles, hepatitis

Non-communicable disease

cannot be spread from host to host - food poisoning, tetanus, Legionellosis

Iatrogenic disease

contracted as the result of a medical procedure

Nosocomial disease

acquired in hospital settings

Zoonotic disease

transmitted from animals to humans

Subclinical disease

no noticeable signs or symptoms
(inapparent infection)

stages in the course of an infectious disease

acute disease

disease where symptoms that develop rapidly

chronic disease

disease develops slowly

subacute disease

symptoms between acute and chronic

latent disease

disease with a period of no symptoms when the causative agent is inactive

Koch’s postulates

**cannot be applied to all pathogens

Limitations to Koch’s postulates

1. Postulate 1, assumes that pathogens are only found in diseased, not healthy, individuals

2. Koch’s postulate made the assumption that all healthy test subjects are equally susceptible to disease

3. Koch also assumed that all pathogens are microorganisms that can be grown in pure culture (postulate 2) and that animals could serve as reliable models for human disease

Molecular Koch’s postulates applied to EHEC

• created by Stanley Falkow - 1988
  • Premise is not the ability to isolate a particular pathogen but rather to identify a gene that may cause the organism to be pathogenic

Pathogenicity

Capacity to produce disease – what does it depend on?

Virulence

intensity of the disease produce by the pathogen

Attenuation

weakening of the disease-producing ability of the pathogen

Virulence factors

1. Have a negative impact on the host

2. enable a host to replicate and disseminate within a host in part by subverting or eluding host defenses.

3. Lead to an increase of mortality rate

4. Enable competition between microorganisms

Median infectious dose (ID₅₀):

is the number of pathogen cells or virions required to cause active infection in 50% of inoculated animals

Median lethal dose (LD₅₀):

the number of pathogenic cells, virions, or amount of toxin required to kill 50% of infected animals

Primary pathogen

pathogen that always causes disease

Opportunistic pathogen

can only cause disease when the host’s defenses are compromised

Steps of pathogenesis

1. exposure or entry

2. adhesion (tissue attachment and colonization)

3. invasion

4. infection/ host damage

5. pathogen exit

   **pathogens are characterized by the presence of virulence factors

Portals of entry into the host

How do organisms cause disease once they enter the host?

Virulence Factors:
1. Adhesion molecules
2. Toxins and superantigens
3. Enzymes

Examples of Virulence factors

o Bacterial Pili
o Enzymes that harm the host or prevent detection
o Proteins that disrupt normal cellular function
o Capsules
o Enzymes that inactivate antibiotics

What happens once the microorganisms enter the host?

• In order to colonize or penetrate the body surfaces/organs, microorganisms first need to attach the surface (adhesion)

Adhesion

Ability of a pathogen to attach to the cells using adhesion factors (adhesins)

Where are adhesins/ ligands located on the pathogen?

1. Can be proteins or lipids and are present on:
   • Pili
   • Flagella
   • Cilia
   • Capsids
   • Membranes of viruses

2. Can be hooks and barbs

3. Can be spike proteins on viruses
4. Can be glycocalyces – slime layers and capsules
5. Biofilm growth can also act as an adhesion factor.

Examples of adhesins on microorganisms

• Glycocalyx: Streptococcus mutans
• Fimbriae: Escherichia coli
• M protein: Streptococcus pyogenes

What happens once microorganisms attach to their target cells?

1. Remain attached to the cell surface – e.g. Taenia saginata
2. Fuse with the host cell membrane.
3. Be internalized into the host cell

How are microorganisms internalized into the host cell?

1. Zipper mechanism

2. Trigger mechanism

3. engulfment due to coating of particles

Exoenzymes

Enzymatic virulence factors help bacteria
invade tissue and evade host defenses

Examples of exoenzymes and their targets

Toxin

substance that contributes to pathogenicity

Toxigenicity

ability to produce a toxin

Toxemia

presence of toxin in the host’s blood

Toxoid

inactivated toxin used in a vaccine

Antitoxin

antibodies against a specific toxin

Exotoxins

proteins produced inside pathogenic bacteria, most commonly gram- positive bacteria, as part of their growth and metabolism. The exotoxins are then secreted into the surrounding medium during log phase

Endotoxin

Lipid portion of lipolysaccharides (LPS) that are part of the outer membrane of the cell wall of gram- negative bacteria- they are liberated when the bacteria die and the cell wall breaks apart. (ex. Salmonella typhimurium)

Characteristics of endotoxins

Characteristics of Exotoxins

Examples of toxins and how they act

Two- Subunit AB Toxins

• A subunit is toxic.
• B subunit binds host cell receptors.
• Many B subunits are complexes of 5 units arranged as a ring.
• ADP-ribosyltransferase inactivates or alters target proteins.

Successful multiplication of the pathogen leads to

infection

Primary infection

acute infection that causes the initial illness

Secondary infection

opportunistic infection after a primary (predisposing) infection

Local infection

pathogens are limited to a small area of the body

Systemic infection

an infection throughout the body

Focal infection

systemic infection that began as a local infection

Sepsis

toxic inflammatory condition arising from the spread of microbes, especially bacteria or their toxins, from a focus of infection

Bacteremia

bacteria in the blood

Septicemia

growth of bacteria in the blood

Toxemia

toxins in the blood

Viremia

viruses in the blood

How pathogens survive within a host

Examples of extracellular immune avoidance

• capsules

• cell-surface proteins

• quorum sensing

Capsules

coat bacterial cell walls and can prevent
phagocytes from binding

Cell-surface proteins

components of the cell wall that prevent detection

• Bind to Fc region on antibodies
• Alter their antigens to avoid antibody binding

Quorum sensing

used to communicate with other pathogens about population size

Antigenic Variation (ex. rhinovirus)

100 known serotypes of rhinovirus; each virus has a unique capsid protein. Antibodies to one capsid protein are not effective on another

Antigenic shift (ex. influenza)

Two strains of influenza virus infect the same cell and the genomes get mixed. This makes a dramatically different virus

Antigenic drift

Random mutations can occur within the cell that a virus infects creating small changes in virus proteins

Latent Herpes Virus

• Herpes virus goes into latency and incorporates it’s genome into the host cell.

• During periods of stress, the virus re-circularizes and reactivates causing lesions.

• Small RNA molecules called microRNAs (miRNA) are made by herpes virus that interfere with the host cell’s apoptosis program.

• During this process, no viral proteins are made to avoid immune detection

Examples of protozoan pathogenesis

• antigenic masking

• antigenic variation

• intracellular location

• immunosuppression

antigenic masking

Some protozoans coat themselves in host antigens to avoid detection by the immune system

antigenic variation

Just like viruses and bacteria, some protozoans can alter their surface antigens to prevent antibody binding

Intracellular Location

Just like some bacteria, protozoans have found ways to live inside the host cell to prevent detection.

Immunosuppression

Some protozoans induce the secretion of anti-inflammatory cytokines to reduce the innate immune response

Exits pathogens use from host