Week 2: i. Concepts in Microbial Pathogenesis 1 & 2 Flashcards
What is Pathogenicity?
- Capacity/Ability of an organism to cause disease (damage + harm) in a host
Pathogenicity:
- Organism needs to be able to: (4)
o Transmit (communicability): From one host/reservoir to another
o Infect: Ability to breach the new host’s defences (skin, mucous membranes, cilia in
respiratory tract – Innate defence mechanisms).
o Survive: In the new host
o Be virulent: Ability of a pathogen to harm a host
Virulence: Degree of damage that the organism causes.
Types of Bacterial Pathogens: (2)
- Opportunistic
- Primary
What are opportunistic pathogens? (2)
- Organisms that only cause disease if the opportunity arises. Can colonise a host but rarely
cause disease in healthy individuals (IS is fully functional). - Rarely cause disease in immunocompetent individuals.
Opportunistic Pathogens:
- If immunological/anatomic _____are compromised, these bacteria can cause disease.
Examples: Skin/mucosal wounds – Entry point into the host. Urinary catheters that bypass the natural defences in the urethra and allow for organisms to ascend into the bladder. ______ tubes that facilitate bacterial entrance into the respiratory system. Venous line that causes skin breakage and facilitates entry of pathogens into the body. - Often _____ flora.
defences
Endotracheal
normal
- Become pathogenic in the absence of normal defence mechanisms ±removal of competing
bacteria (e.g. broad spectrum antibiotics).
Antibiotics do not only remove pathogenic bacteria. Leads to a disturbance in the balance of organisms, allowing certain organisms to “take over” and cause harm. - Example:
- Example: Coagulase Negative Staphylococci (CNS)
Staphylococci found as part of the skin flora and are usually harmless/don’t cause disease. But, under certain circumstances they can cause disease. In premature babies (reduced immunity) with multiple lines and catheters that breach anatomical defences - CNS must be treated.
- Example: As immunity declines with HIV (CD4 count as marker of immune competency), there is increased opportunistic infections by opportunistic _______.
Over time the CD4 count declines, and the more __________ the person becomes – Increased risk of various opportunistic infections. Spectrum of opportunistic diseases the patient presents with depends on the ____ level (some diseases only appear when CD4 count is extremely low – Non tuberculosis mycobacterium)
pathogens
immunocompromised
CD4
What are the primary pathogens? (3)
- Able to cause disease in healthy immunocompetent individuals
- BUT may more readily cause disease in individuals with impaired defences
Impaired defences: Elderly, HIV-positive patients - Example: Streptococcus pneumoniae, Salmonella Typhi (‘Typhoid Mary’)
What is virulence? (5)
Why do bacteria need virulence factors? (5)
What is Quorum Sensing (QS)?
- Mechanism used to express virulence factors within a bacterial population. Virulence genes may be present but not always active/switched on.
Quorum Sensing (QS):
- Type of communication between bacterial populations – Use chemical signalling molecules (autoinducers/pheromones) to regulate gene expression so that the whole population can act in a _____ way. Allows individual bacteria to carry out coordinated ____-_____ functions – More effective than a single action of bacteria.
- Bacteria secrete and produce the ______ during their reproductive cycle. Molecules move out of the cells and accumulate in the environment – At a critical concentration level/threshold, ____ ______ for the entire population is triggered.
unified
colony-wide
autoinducers
gene expression
Establishing infection:
- Pathogen entry: (4)
- Skin (Breach, tick bites, mosquito bites)
- Respiratory tract (Droplets, aerosols)
- Gastrointestinal tract (Ingestion)
- Urinary/genital tract (Catheter, sexual transmission)
- Some pathogens require specific contact:
o Example: Treponema pallidum (syphilis
Why does this occur? (2)
o Requires direct skin to skin contact (Contact with a genital ulcer that contains treponema can transmit the infection from one person to another)
o Humans are the only host - They will die in the environment
- Source of infection: Individuals with clinical disease or carriers
o Carrier:
o Example:
- Source of infection: Individuals with clinical disease or carriers
o Carrier: individuals in whom symptoms may be absent or relatively mild because the
disease process is at an early stage or because of partial immunity to the pathogen
o Example: Typhoid Mary - Woman who lived in NY, beginning of 19th century, worked in several households as a cook – Asymptomatic carrier of Salmonella Typhi. Thought to be the main cause of a huge outbreak.
- Other pathogens may be able to infect humans and animals.
Example: Salmonella spp, Shigella spp, Campylobacter spp
Organisms that cause _______. When excreted with stool into the environment, can contaminate food and water sources – Infection when ______.
gastroenteritis
ingested
o Source of infection: Contaminated food or water in the environment
o Animals
1. Reservoir of _____ (animals are infected, but do not get sick)
2. Source of environmental ______
infection
contamination
Define colonization:
- Definition: The establishment of a stable population of bacteria in the host.
What are the requirements for colonization? (4)
- Requires adhesion to a mucosal surface
- This allows for a focus of infection to develop, which may lead to localised infection/
systemic spread. - Adhesion involves surface interaction between host cell receptors and adhesins on bacterial
surface. - Presence or absence of cell receptors contribute to tissue specificity of infection. Some organisms can only infect certain parts of the body/certain types of tissue (where receptors found that match the adhesin of the bacteria). Host cells have cell surface proteins to which the organism attaches – VERY SPECIFIC (Needs to be a match between the host cell receptor and adhesin of the organism).
Colonization:
- Consequence of adhesion: (2)
o Induces changes in bacterial expression
o Induces intracellular signalling pathways (eventually leads to invasion)
What are the types of adhesins? (2)
o Fimbrial adhesins
o Non-fimbrial adhesins
What are the features of fimbrial adhesins? (4)
▪ Thin, rigid, rod-like structure
▪ Mediate attachment to cell
▪ Found in Gram-positive (GP) and Gram-negative (GN) bacteria
▪ Example: E.coli colonization factor antigen I and II (Traveller’s diarrhoea or
diarrhoea in infants). Antigens I and II initiate the adherence of bacteria to mucosa in the intestine.
What are the features of non-fimbrial adhesins? (3)
▪ Protein or polysaccharide structures that are on the bacteria cell or
excreted.
▪ Found in GP and GN bacteria
▪ Example: Teichoic acid (Bacteria cell wall of GP) - CNS
Flagella (Appendage used for movement + attachment. Various numbers
and positions on different organisms) - Vibrio cholerae
How is fibronectin bound? (2)
o A complex human glycoprotein found in plasma (ECM – meshwork of secreted proteins within the space between cells), associated with mucosal surfaces and promotes adhesion functions.
Binds to other proteins in the ECM (collagen and fibrin) – General cell adhesion molecule by anchoring cells to substrates.
o Many bacteria use fibronectin for adhesion purposes
What is the process of invasion? (2)
- Some bacteria are able to cause disease after colonisation.
- Most bacteria need to invade cells/tissue.
Invasion:
- Some bacteria which are able to survive within the host cell:
- Treatment:
- Some bacteria which are able to survive within the host cell: Mycobacteria, Salmonella,
Shigella, E.coli, Listeria, Neisseria species. - Treatment: Use antimicrobials that can target organisms within the host cells.
What are the features of cell invasion? (3)
o Ability to avoid humoral defence mechanisms
Shields organism from various extracellular host defences (protection)
o Provide a niche rich in nutrients
o Provide protection from other bacteria
What is the process of uptake into host cells? (3)
o Usually use phagocytic entry mechanisms
o Some organisms remain in the superficial cell layers (localized infection)
Example: Shigella spp.
o Others invade into deeper tissue (causing systemic infection)
Example: Salmonella spp.
What is the role of cell receptors in cell invasion? (2)
o Availability of specific receptors defines the types of host cells involved
o Specific host receptors have been identified for some organisms
Example: M. tuberculosis - Complement receptors on phagocytes
Survival & Avoiding Host Defence:
- Survival and multiplication:
o To cause disease, microorganism must be able to survive on/in: (3)
▪ Epithelial surfaces
▪ Lumen
▪ Host tissue
Survival & Avoiding Host Defence:
- Survival and multiplication:
o Survival depends on ability to … the host defences: (3)
▪ Avoid
▪ Evade host defences
▪ Resist
o Multiplication depends on acquiring necessary ______.
nutrients
Survival & Avoiding Host Defence:
- Avoid host defence: (5)
o Humoral immune responses
o Cell-mediated immune response
o Complement
o Lysozyme
o Iron chelators - Transferrin, lactoferrin
Virulence factors that avoid Host defence: Capsule
Mechanism:
Example:
Mechanism: Aids in avoiding phagocytosis by shielding organism.
Example: Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae
Virulence factors that avoid Host defence: Streptococcal M Protein (Virulence factor)
Mechanism:
Example:
Mechanism: Not a capsule but avoids phagocytosis in a similar manner
Example: Streptococcus pyogenes
Virulence factors that avoid Host defence: resistance to killing by phagocytic cells
Mechanism:
Example:
Virulence factors that avoid Host defence: Antigenic Variation
Mechanism:
Example:
M: Change of antigen or DNA sequence to avoid an immune response against that antigen (immune system unable to recognise)
E: Neisseria meningitidis
- PorA amino acid mutations - Switch off expression of capsule
Virulence factors that avoid Host defence: IgA Proteases (IgA is supposed to prevent colonization by invading organisms by binding to them)
Mechanism:
Example:
M: A protease that specifically cleaves IgA at mucosal surfaces
E: Meningitis- causing pathogens
Virulence factors that avoid Host defence: Serum Resistance
Mechanism:
Example:
M: Resist lysis as a result of deposition of complement on the bacterial surface
E: O1 polysaccharide
Sialic acid capsule in E.coli K1
Virulence factors that avoid Host defence: Iron Acquisition
(Iron is NB nutrient for bacterial metabolism)
Mechanism:
Example:
M: Scavenge iron from mammalian iron-binding proteins
E: Staphylococcus aureus - Specific receptors for transferrin and lactoferrin
Toxins: Major virulence factor
Function:
- Exert their pathogenic effect on a target cell/interact with cells of the immune system to release cytokines that cause pathophysiological effects
- Endotoxins: (5)
o Lipopolysaccharide
o Component of outer membrane of GN bacteria
o Released from the bacterial surface via vesicles
o Causes endotoxic /septic shock
o Activate macrophages, thus inducing a range of cytokines (Proteins excreted by cells
of the IS, regulate immune response and degree of inflammation)
- Exotoxins: (2)
o Diffusible proteins secreted into the external medium
o GP and GN bacteria
How do exotoxins vary?
o Vary in molecular structure, function, mechanism of secretion and immunological properties: Based on which part of the host cell they are active
What are the types of exotoxins? (3)
Toxic effect: Lethal Action
Location/site:
Example:
Location/site: Effect on neuromuscular junction
Example: Clostridium botulinum toxin A
Toxic effect: Pyrogenic Effect
Location/site:
Example:
Location/site: Increased body temperature and polyclonal T cell activation
Example: Staphylococcal Toxic Shock Syndrome Toxin 1
Toxic effect: Action on GIT
Location/site:
Example:
Location/site: Secretion of water and electrolytes in GIT
Example: Cholera and E.coli enterotoxins
Toxic effect: Action on skin
Location/site:
Example:
Location/site: Necrosis
Example: Clostridium perfringens toxins
Toxic effect: Cytolytic effects
Location/site:
Example:
Location/site: Lysis of blood cells
Example: Streptolysin O and S (S. pyogenes)
Toxic effect: Inhibition of metabolic activity
Location/site:
Example:
Location/site: Protein synthesis
Example: Diphtheria toxin
Human-microbe interactions:
What is normal flora?
Human-microbe interactions:
What are obligate pathogens? (4)
o Must cause disease in humans in order to survive.
o Wide range of symptomatology (asymptomatic to severe disease)
Doesn’t cause the same kind of disease pattern in every person.
o Example: Smallpox, M. tuberculosis
o Cannot kill all hosts, otherwise it won’t survive
What are accidental/incidental Pathogens?
o Causing disease offers no advantage, and may in fact be a dead end to lifecycle
- Accidental/incidental Pathogens:
o 2 types:
- Pathogens in the Environment:
o Whatever the environment, pathogen must be able to survive long enough to
encounter a ________ host.
o Dynamics of pathogen survival in different environments are relevant to control of
infection.
We must be able to identify what the reservoir is, how the organism survives – Mechanisms to prevent _____ and _____.
o Examples: ____ _____ spreads in water (Public health infection control method), Methicillin Resistant Staphylococcus aureus hospital acquired (Infection-prevention and control efforts must be focused on in a hospital environment).
Susceptible
Spread and infection
Vibrio cholerae
Pathways to and Stages of Infection:
(Following an encounter between a host and microorganism)
Blue (possible outcomes for pathogen), Yellow (possible outcomes for non-pathogen), Green (Pathogen or non-pathogen). For example, a pathogen would encounter a host. Initially, there needs to be entry and establishment of pathogen in host. At that point a variety pf possibilities can occur: Colonisation (B) and then end. Brief period of colonisation then infection develops (C). Colonisation for long enough that it becomes part of the normal microbiota and thereafter, it can develop infections (D). Directly from entry to establish an infection (A). Some infections may become symptomatic only when the level of damage/dysfunction is sufficient. At the end of the symptomatic infection, a small number of pathogens may enter the normal microbiota (E) – Have normal infection, then becomes part of microbiota, host is described as a carrier of organism. For non-pathogen, encounter with transition (F) into colonization post-infection - Carrier.
Timescales for Key Events in Infection:
Incubation period:
Acute:
Subacute:
Chronic:
NOTE: Innate immune response is always a few days long, irrespective of acute/subacute/chronic infection. Adaptive immune response always comes into play at the same time. HOWEVER, for each type of infection the innate or adaptive immune response plays a more important role.
With an acute infection, it is only the innate immune response that plays a role. With subacute, the adaptive immune response plays a large role with a little role for the innate immune response. For chronic, it is purely an _______ immune response.
adaptive
4 Pathological Patterns of Infection:
What is a Toxin Mediated Bacterial Infection? (5)
What is an Acute Pyogenic Bacterial Infection?
- Pus inducing infections (pus indicates infection is bacterial in nature)
What are the types of Acute Pyogenic Bacterial Infection? (2)
- 2 TYPES: Localized or disseminated (involving the body systemically)
What are the features of Acute Pyogenic Bacterial Infection? (7)
What are Subacute Bacterial Infections? (4)
What are Chronic Granulomatous Bacterial Infections? (6)
Patterns in the Presentation and Pathology of Bacterial Infection: Toxin-mediated Disease (3)
Patterns in the Presentation and Pathology of bacterial infection: Acute Pyogenic Infection (3)
Patterns in the Presentation and Pathology of bacterial infection: Subacute infection (3)
Patterns in the Presentation and Pathology of Bacterial Infection: Chronic (Granulomatous) (3)
Timing of Key Events in Infection
- Incubation Period: (2)
The time between the encounter with the pathogen and the onset of symptoms.
o Important in infection control
o Important to determine infectivity of a patient and risk of transmission
- There are a number of different key events and a variety of clinical presentations associated with these infections. In these graphs we can describe the different clinical _______ and outcomes associated with each. If we assume we have 3 different organisms, each with the same _______ period, and each with the same number of organisms required to cause clinical infection. Horizontal dotted line: How much organism is required to cause ______ disease.
manifestations
incubation
clinical
Describe the top graph.
- TOP GRAPH: Certain patients will have asymptomatic infection (red line), some patients may develop clinical infection, and if remain undiagnosed and untreated would continue down severity of infection, eventually leading to death (blue line). Patients who recover, either as a result of the IS or effective treatment (green line).
Describe the middle graph.
- MIDDLE GRAPH: Asymptomatic infection (red line), infection with increased severity resulting in death (blue line). But in certain patients it may result in recurrent symptoms. With adaptive IS at play, there may be some reactivation and dampening from the adaptive IS (light blue – up and down recurrent symptoms).
Describe the bottom graph.
- BOTTOM GRAPH: Asymptomatic infection (red line), severe infection resulting in death (blue line). Treatment or IS-based recovery (green line). Latent infection (pink line) where after recovery a person is not able to clear the organism, organism remains in the body in a dormant phase (TB and Syphilis). Usually when you have this component of latent infection, it can at a later stage result in reactivation (yellow line).
What is the relationship between dose and outcome? (5)
- There is a quantitative relationship between an organism dose the outcome.
- The organism is administered by a single root to a population of very similar people. The outcome depends on the dosage of organism.
- Allows virulence to be compared between different strains of a particular microorganism:
The more virulent organism shifts the curve to the left (Lower dose is required to cause severe infection) – BLUE LINE
Less virulent organism shifts the curve to the right (Higher dose is required to increase the
number of people infected) – RED LINE - The lesser/greater host resistance would have the same effect: A person with a stronger IS would also require a higher dose of organism to cause infection. Whereas a person with a weaker IS would require a smaller dose of organism to cause infection.
- ID50: 50% infected endpoint. The dose required to produce the specified endpoint in 50% of the target population is reproducible and can be used for statistical analysis.
