3 Pathogenesis & Virulence

capacity of a microbe to cause damage in a host

Virulence is the measure of pathogenicity of an organism and refers to the degree of damage caused by the microbe

• Virulence is a continuum

• On one end of the spectrum are organisms that are avirulent (not harmful, ) and on the other are organisms that are highly virulent (e.g. B. anthracis)

A product made by the organism that contributes to overall virulence (e.g. toxin). They help bacteria to (1) invade the host, (2) evade host defenses, and (3) cause disease

Small, metabolically inactive forms of bacteria that can survive for years (extremely tough outer coating)

Iron-binding factors that allow some bacteria to compete with host for iron (e.g. Enterobactin)

median infectious dose (ID50)

• number of pathogen cells required to cause active infection in 50% of inoculated animals

median lethal dose (LD50)

• number of pathogenic cells or amount of toxin required to kill 50% of infected animals

A primary pathogen can cause disease in a host regardless of the host’s resident microbiota or immune system

An opportunistic pathogen, by contrast, can only cause disease in situations that compromise the host’s defenses, such as the body’s protective barriers, immune system, or normal microbiota

• Individuals susceptible to opportunistic infections include:

• Very young

• Elderly •

• Pregnant women •

• Chemotherapy patients •

• People with immunodeficiency's •

• Patients recovering from surgery •

• Via a breach of protective barriers (such as a severe wound or burn)

enterohemorrhagic E. coli

• Produces a virulence factor known as Shiga toxin

• Toxin inhibits protein synthesis, leading to severe and bloody diarrhea, inflammation, and renal failure, even in patients with healthy immune systems

Staphylococcus epidermidis

• among the most frequent causes of nosocomial (i.e. hospital acquired) disease

• Member of the normal skin microbiota (30% carriage rates) → generally avirulent

• However, in hospitals, it can also grow in biofilms that form on catheters, implants, or other devices that are inserted into the body during surgical procedures

• Once inside the body, S. epidermidis can cause serious infections such as endocarditis, and it produces virulence factors that promote the persistence of such infection

Can cause haemolytic uraemic syndrome (HUS) in humans (especially children)

• From cattle

1. Exposure (contact)

2. Adhesion (colonisation)

3. Invasion

4. Infection

• Pathogen must be able to gain entry to the host → travel to the location where it can establish an infection → evade or overcome the host’s immune response → cause damage (i.e., disease) to the host

• In many cases, the cycle is completed when the pathogen exits the host and is transmitted to a new host

capability of pathogenic microbes to attach to the cells of the body using adhesion factors

Local infection is confined to a small area of the body, typically near the portal of entry

• E.g. Urinary tract infections (UTIs) confined to the bladder

Focal infection, a localised pathogen, or the toxins it produces, can spread to a secondary location

•E.g. Dental focus most common, e.g. gum disease or nicking the gum with a sharp tool can lead to a local infection by Streptococcus of the normal oral microbiota → Streptococcus spp. may then gain access to the bloodstream and make their way to other locations in the body, resulting in a secondary infection

systemic infection, when an infection becomes disseminated throughout the body

• Pathogen must overcome host defenses in order to cause systemic infection

• Damage to the host can be direct e.g. via virulence factors such as toxins, or may result from host immune-mediated damage (sepsis)

Sepsis occurs when chemicals released into the bloodstream to fight an infection trigger inflammatory responses throughout the body.

Insertion of ‘foreign’ DNA inserted into bacterial chromosomes

• Frequently encode virulence associated traits

• e.g. Salmonella pathogenicity island 1 (SPI1) – encodes Type 3 secretion system (injector) that is key for host cell attachment vs. SPI2 (survival within macrophages)

• Sometimes a primary infection, the initial infection caused by one pathogen, can lead to a secondary infection by another pathogen

• Antibiotic therapy targeting the primary pathogen can cause collateral damage to the normal microbiota, creating an opening for opportunistic pathogens

• E.g. Clostridiales difficile