Bacterial Pathogenesis I - L7 Flashcards
What is bacterial pathogenesis?
the mechanism by which a bacterial pathogen produces disease
What is a bacterial pathogen?
a bacteria that is capable of causing disease in a host
Virulent pathogen
exceedingly pathogenic organism
avirulent organism
not pathogenic
attenuated pathogen
less pathogenic organism
primary pathogen
disease causing pathogen that can cause disease even in a healthy host
opportunistic pathogen
can cause disease only in a compromised host; do not cause disease under normal conditions but can cause disease under special conditions
How do you show that a suspected pathogen is the cause of a particular disease?
Koch’s Postulates
What are Koch’s Psotulates?
- the organism must be present in every case of a disease (but absent from healthy)
- the organism must be isolated from diseased host and cultivated in pure culture
- the cultivated organism must cause the same disease when inoculated into a naive host
- the organism must be recovered from the newly diseased host
What are problems with Koch’s Postulates?
a. some bacteria and all viruses can only be grown in eukaryotic cells
b. some agents cannot be cultured or no suitable animal model is available
mutualistic
both organisms benefit from the relationship
commensalistic
one organism benefits while the other neither benefits or is harmed
parasitic
one organism benefits (parasite) from the relationship and the other organism (host) is harmed
colonization
establishment and multiplication of a microorganism (pathogen or non-pathogen) in a host
infection
refers to the multiplication of a PATHOGEN in a host with or without disease (ex. asymptomatic carriers)
disease
occurs when an infected host is injured or damaged in a manner that impairs host function
When does bacteria colonization begin?
during or soon after birth
What is normal flora/microbiota/microbiome?
bacteria that establish permanent colonies inside of on the body without producing disease
bacterial antagonism
the normal flora can prevent colonization by pathogens
How many microorganisms normally reside in or on the body?
1x10^14 in total; 500 to 1000 species of bacteria live in the human gut, with a similar number on the skin
What kind of relationship do we have with normal flora?
previously commensalism;
currently it plays a critical role in our health and development
Characteristics of skin flora?
- a dry, acidic environment
- primarily moist areas colonized (associated with sweat glands)
- mainly gram positive bacteria
Characteristics of oral cavity flora?
- dental plaque = biofilm
- dental procedures can allow bacteria into bloodstream
Characteristics of GI flora?
- stomach kills most bacteria
- intestine = hella, higher pH
What are the benefits of the microbiota?
help digest food, required for healthy immune system, synthesis of vitamin B12 and vitamin K
What affects microbiota composition?
antibiotics, stress, changes in diet
what are probiotics?
supplemental beneficial bacteria that can help restore normal balance and composition of the microbiota
Characteristics of respiratory tract flora?
- upper heavily colonized
- lower essentially sterile
what is the mucociliary elevator?
cilia and mucous trap bacteria in the throat and move them to the mouth for swallowing to the stomach
Characteristics of urogenital tract flora?
- kidneys and bladder normally sterile
- outer parts are colonized with normal flora
Why are antibiotics such an issue right now?
- average kid gets 10-20 courses before 18
- they target pathogens AND beneficial bacteria
- open doors for opportunistic pathogens like MRSA and Clostridium difficile
- use in food is affecting humans as well
What does a pathogen have to do to cause disease?
- contact the host
- colonize/infect the host
- evade host defense systems
- damage host cells/tissues
virulence factors
factors responsible for the virulence of a pathogen
Types of virulence factors?
adhesins, invasins, evasins, toxins, and degradative enzymes
Where are virulence factors found?
on mobile genetic elements or pathogenicity islands
pathogenicity islands
chromosome islands that have different GC/AT ratio that the rest of the chromosome
Old School host interaction
bacteria contact host cells/tissues
attach, grow and multiply locally or spread to deeper tissues
release toxins
new school host interaction
pathogens employ complex virulence strategies to manipulate host cell responses and to promote their survival/transmission (T3SS)
Enteropathogenic E. coli (EPEC)
causative agent of infantile diarrhea; interaction of organism with intestinal epithelial cells (attaching and effacing lesions)
What are common portals of entry?
- urogenital tract (STDs, UTIs)
- digestive tract (contaminated food/water)
- respiratory tract (airborne)
- Conjunctiva/eye (chlamydia/trachoma)
- damaged skin (staphylococcal infections)
- injection (insects - parenteral route)
How do pathogens move past colonization?
must adhere to eukaryotic cells or tissue and withstand host’s defenses
Adhesins
bacterial cell surface proteins that bind to specific host receptors on epithelial or exposed cells
what are the two steps of bacterial adhesion?
- Initial loose attachment
- pili, biofilms, slime layers, LPS - strong or intimate attachment
- bacterial nonpilus adhesins
biofilm
bacteria attached to surfaces in bulk, plus an extracellular polymeric substance (EPS)
Why are biofilms important?
play an important role in chronic infections by helping with persistent adherence and resistance to host and antimicrobial defenses
How do invasive bacteria spread?
- releasing toxins
- penetrating barriers to deeper tissues
- via blood or lymph circulation
Where do invasive bacteria spread?
specific organs or to whole system
Bacteremia
bacteria in blood
Septicemia
bacteria growing and multiplying in blood
extracellular pathogens
attach to receptor molecules on host cell surface and remain extracellular (like cholera)
intracellular pathogens
invade host cells and multiply inside these cells (in membrane vacuole or outside cells)
facultative intracellular pathogens
can grow inside cells or outside - salmonella, shigella, listeria
obligate intracellular pathogens
only grow inside eukaryotic cells - chlamydia, rickettsia
Intracellular life advantages vs disadvantages
- difficult for host to attack without autophagy or apoptosis
- intracellular bacteria safe from antibodies, complement proteins, and some antibiotics
- access to host cell nutrients
- must exit cells at some point to exit host and be transmitted to a new host
extracellular life advantages vs. disadvatages
- pathogen must deal with antibodies, complement system, etc.
- pathogen must compete with normal flora and other pathogens
- provides greater opportunity for rapid growth, reproduction and spreading
What defense systems do pathogens have to avoid?
- destruction by phagocytosis
- complement mediated lysis and host antibody response
- destruction in the phagosome
- antimicrobial peptides
- reactive oxygen and nitrogen species
- the cell mediated immune response
- apoptosis
What is complement-mediated bacterial lysis (what is the complement system)?
refers to a series of proteins circulating in the blood in an inactive form that can be activated by certain host or microbial products
How can complement be activated?
- antibody binding to the bacterial surface (classical pathway)
- bacterial polysaccarides/LPS (alternative pathway)
What is the result of the complement system?
- generation of products that label or opsonize the bacteria
- results in the formation of a membrane attack complex (MAC) that lyses gram-negative bacteria
Serum resistant bacteria
bacteria not killed by the complement MAC
What are mechanisms of serum resistance?
- capsules (inhibit opsonization, hide bacterial components that induce pathway)
- modification of LPS O-antigen
- release proteases that degrade complement components
- binding of complement regulatory components to the bacterial surface
How do bacteria avoid host antibody responses?
pathogens often coat themselves with normal host antigens (fibronectin, antibodies) or bacterial products (hyaluronic acid) that cannot be distinguished from host antigens
antigenic variation
many bacteria can change the antigens of key exposed surface products (ex. Neisseria spp. pili)
phase variation
bacteria can turn the expression of certain key antigens off and on during an infection
What are two functions of bacterial products?
- destroy host immune cells
- aid in spread/transmission of the infection
What are the two general classes of toxic molecules produced?
- endotoxin (LPS) - associated with outer membrane
2. exotoxins - enzymes and toxins that are released from bacterial cells and function at a distance
Key facts about endotoxin (LPS)?
- produced by only gram-neg
- part of cell wall
- LPS
- low toxicity (large dose needed)
- heat stable
- systemic effect
- cannot be converted to safe form (not immunogenic)
Key facts about exotoxins?
- produced by both gram-pos and gram-neg
- extracellular, secreted
- proteins
- high toxicity (hella toxic, you gon die)
- heat labile (change in heat)
- highly specific target/effect
- highly immunogenic (can be inactivated and made into a vaccine/antiserum)
How does a pathogen get to the next host?
- oral-fecal route: diarrhea (EPEC, vibrio cholerae)
- aerosols: sneezing and coughing (mycobacterium tuberculosis)
- direct sexual contact/sexual transmission (chlamydia trachomatis)
- other vectors (insects, etc.)
A summary of bacterial pathogenesis:
- contact the host (transmissible)
- colonize/infect the host (adhere to surfaces + multiply)
- evade host defense systems (prevent clearance, find a niche, avoid/subvert/circumvent defenses)
- damage host cells/tissues (spread, release nutrients)
- Disseminate (transmissable - GTFO)
