Lectures 13&14: Pathogenicity of Microorganisms Flashcards
Parasites are organisms that
- Live on or within a host organism and are metabolically dependent on the host
- are any organism that cause disease
The host is
larger organism that supports the survival and growth of a smaller organism
Infection
- A parasite growing and multiplying within/on a host
- may or may not result in overt infectious disease
Pathogen
- Any parasite organism causing infectious disease
Primary (frank) pathogen
Causes disease by direct interaction with healthy host
Opportunistic pathogen
May be part of normal flora and causes disease when it has gained access to other tissue sites or host is immunocomprimised
Pathogenicity
ability to cause disease
Chain of events for a successful infection
- agent identitiy
- virulence of agent
- means of exposure to agent
- dose of agent
- susceptibility of host to agen
infections passed from animal to human are termed
zoonoses
What does animate mean
from other humans or animals
what does inanimate mean
from water, soil, and food
Natural enviromental location in which the pathogen resides
Reservoir (can be animate or inanimate)
organisms that spread disease from one host to another
vector
infectious disease
infection with viruses, bacteria, fungi, protozoa, and helminths
Objective changes in body that can be directly observed
Signs
subjective changes experienced by patient
symptoms
Set of characteristic signs and symtpoms
disease syndrome
Incubation period
period after pathogen entry, before signs and symptoms
Prodromal stage
- Onset of signs and symptoms
- not clear enough for diagnosis
Period of illness
- disease is most severe, signs and symptoms
Convalescence
Signs and symptoms begin to disappear
Course of infectious disease
- Incubation period
- Prodromal stage
- Period of illness
- Convalescence
A pathogen must contact a host and survive within it to cause a disease. To survive, it needs
- A suitable environment
- A source of nutrients
- in competition with eukaryotic host cells
- Protection from harmful elements
- virulence factors allow a pathogen to oucompete host cells and resist their defenses
Some survival strategies for pathogens once in the host are
- Adhesins
- Enzymes
- Toxins
- Invasins
- Autoinducers
Virulence factors determine the
degree to which a pathogen causes damage, invasion, infectivity
What is virulence
degree or intensity of pathogenicity
Virulence is determined in part by pathogen’s ability to
- survive outside of host
- more dependent on host (cannot survive outside of host)= less virulent
*
- more dependent on host (cannot survive outside of host)= less virulent
What does pathogenicity islands mean
- Major virulence factors on large segments on chromosomal or plasmid DNA
- Increase bacterial virulence
- absent in nonpathogenic members
- common sequence characteristics
- insertion-like seqquences for mobility
- G + C content different from bacterial genome
- several open reading frames
- Can be spread through horizontal transfer of virulence genes to bacteria
What is the first step in disease
- entrance and attachment
- Portal of entry
- Skin, respiratory, gastrointestinal, urogenital systems, or conjunctiva of eye, parental route (break in barrier defenses)
- Vector borne, sexual contact, blood transfusion, or organ transplant
- Adherence
- medated by special molecules called adhesins
- Colonization
- A site of microbial reproduction on or within host
- does not necessarily result in tissue invasion or damage
- Portal of entry
What are the adherence structures of microbes
- Pili or fimbriae (adhesion molecules on bacterium’s cell surface) bind complementary receptor sies on host cell surface
what is microbial colonization site
- Site of microbial reporduction on/in host
- does not necessarily result in tissue damage
- Adhesin/ligans bind to receptors on host cells
- examples on
- Streptococcus mutans
- Escherichia coli
- Streptococcus pyogenes
- examples on
- Streptococcus mutans: Glycocalyx
- Escherichia coli: Fimbriae
- Streptococcus pyogenes: M protein
Examples of microbial attachment mechanisms in Eschericia coli
- Type I fimbrae ( leads to diarrhea and UTI)
- P pili (leads to Hemolytic uremic syndrome)
Adhesion mechanism of Streptococcus pyogenes
- Protein F (causes strep throat)
Attachement mechanism of streptococcus mutans
sugar residue/glycocalyx (causes dental caries)
Infectivity
ability to create a discrete point of infection
invasiveness
ability to spread to adjacent tissues
Penetration can be active or passive explain both
- active occurs through lytic substances which
- attack the extracellular matrix and basement membranes of integuments and intestinal linings
- degrade carbohydrate-protein complexes between cells
- disrupts host cell surface
- passive (e.g. Skin lesions, insect bites, wounds)
- spread to deeper tissues involves production of specific products and/or enzymes that promote spreading
Virulence factor produced by Staphylococcus aureus for bacterial pathogen invasion and dissemination
Coagulase: Coagulates (clots) the fibrinogen in plasma/ The clot protects the pathogen from phagocytosis and isolates it from other host defenses.
Virulence factor produced by Groups A,B,C, and G streptococci, staphylococci, clostridia for bacterial pathogen invasion and dissemination
Hyaluronidase: hydrolyzes hyaluronic acid, a constituent of the extacellular matrix that cements cells together and render the intercellular spaces amenable to passage by the pathogen
Virulence factor produced by Staphylococci, pneumonocci, and other streptococci for bacterial pathogen invasion and dissemination
Leukocidins: pore-forming exotoxins that kill leukocytes; cause degranulation of lysosomes within leukocytes, which decrease host resistance
presence of viable bacteria in the blood
bacteremia
Pathogens or their toxins in the blood
septicemia
Invasiveness varies among pathogens. Examples
- Clostridium tetani (tetanus) produces a number of virulence factors but is non-invasive
- Bacillus anthracis (anthrax) and Yersinia pestis (plague) also produce many virulence factors and are highly invasive
- Streptococcus spp. span the spectrum of virulence factors and invasiveness
what is toxigenicity
ability to produce toxins
What is a toxin
a specific substance that damages host
Diseases that result from entry of a specific preformed toxin into host (Ex. Tetanus toxin)
Intoxications
Toxemia
condition caused by toxins in the blood of host
Exotoxins
- Soluble, heat-labile, proteins
- secreted into surroundings as pathogen grows
- most exotoxin producers are gram-positive
- often travel form site of infection to other tissues or cells where they exert their effects
- Usually synthesized by specific bacteria that have toxin genes in their plasmids or prophage DNA
- Among the most lethal substances known
- Are highly immunogenic
- Stimulate production of neutralizing Ab (antitoxins)
- Chemically inactivated to form immunogenic toxoids
- e.g. Tetanus toxoid
- do not produce a fever (but they are heat labile)
- LD50 is small
Types of Exotoxins
- AB exotoxins
- Composed of two subunits
- A subunit- responsible for toxic effect
- B subunit- binds to specific target cell
- Composed of two subunits
- Specific host site exotoxins
- Membrane-disrupting exotoxins
- Superantigens
Botulinum toxin
- Organism:
- Clostridium botulinum
- Gene location:
- Prophage
- Toxin type:
- AB
- Mechanism of Action:
- Blocks neurotransmitter release, leading to paralysis (flaccid paralysis)
- specificially it attacks SNAP25 and Syntaxin and does not allow the Ach to be moved to the synaptic terminal and released into the synaptic cleft
Tetanospasmin
- Organism:
- Clostridium tetani
- Gene location:
- Plasmid
- Toxin type:
- AB
- Mechanism of Action
- Blocks neurotransmitter, leadin to spastic paralysis
- proteolysis of Synaptobrevin
Superantigens
- Stimulate about 30% of T cells of the immune system
- Causes the T cells to overexpress and release cytokines
- results in failure of multiple host organs allowing time for the microbe to disseminate
- Example
- Staphylococcal enterotoxin B
Endotoxins
- Lipopolysaccharide (LPS) in Gram-negative cell wall can be toxic to specific hosts
- called endotoxin because it is an endogenous (part) of the bacterium and released when organism lyses
- some is also released during multiplication
- Toxic component is the lipid portion, lipid A
- called endotoxin because it is an endogenous (part) of the bacterium and released when organism lyses
- Heat Stable (but do produce fever)
- Toxic (nanogram amounts)
- Weakly immunogenic
- Generally similar, despite source
- Cause general system effects
- Fever, weakness, diarrhea, inflammation, intestinal hemorrhage, and fibrinolysis, the enzymatic breakdown of fibrin, the major protein component of blood clots
- Bring about these effects indirectly:
- endotoxin interacts with host molecules and cells, activating host systems
- coagulation, complement, fibrinolytic, and kininogen system
- e.g. interaction with macrophages—> release of endogenous pyrogen (induces fever)
- e.g. binding to LPS-binding protein —> release of cytokines
- tumor necrosis and others lead to septic shock
- endotoxin interacts with host molecules and cells, activating host systems
- LD50 is relatively large
- chemistry:
- lipid
- Source:
- Gram-negative
- Not neutralized by antitoxin
Mycotoxins
- Secondary metabolites of fungi
- common contaminants of food crops
- Aspergillus flavus and A. parasiticus produce carcinogenic aflatoxin
- Stachybotrys produce tissue-damaging satratoxins
- Claviceps purpurea (ergot) produce hallucinogen lysergic acid (LSD)
effects of pathogen biofilm growth
- May cause a chronic infection
- increases virulence
- become less sensitive to antibiotics
- make cells in biofilm more resistant to host defense (“frustrates” phagocytes)
Cell wall components of pathogens that are increase virulence
- M protein resists phagocytosis
- ex. Streptococcus pyogenes
- Opa protein inhibits T helper cells
- Ex. Neisseria gonorrhoeae
- Mycolic acid (Waxy lipid) resists digestion
- Ex. Mycobacterium tuberculosis
Resisting host defenses
- Production of decoy proteins to bind available neutralizing antibodies
- Lengthened O-chains to prevent host detection or lysis
- some survive inside host cells
- eject themselves form cell to cell using host actin
- ex. Shigella sp. and Rickettsia sp.
- Infection of immune system cells, diminishing function
- Fuse with adjacent cells to prevent exposure to antimicrobial proteins in host
- Capsules prevent phagocytosis
- Mutations change antigenic sites or alter expression of antigens
- thourhg downregulation or phase variation (ex. Altered Pilin protein, N. gonorrhea)
- Produce substances that resemble host tissue
- Produce proteases that degrade host proteins
- Special proteins that interfere with host defenses
Examples of Capsules and function
- Prevent phagocytosis
- Streptococcus pneumoniae
- Haemophilus influenzae
- Bacillus anthracis
- Staphylococcus aureus
Pathogen Enzymes
- Coagulase
- Coagulates fibrinogen
- Kinases
- Digest fibrin clots
- Hyaluronidase
- Hydrolyzes hyaluronic acid (found in CT)
- Collagenase
- Hydrolyzes collagen
- IgA proteases
- Destroy IgA antibodies
Evidence suggests correlation between mode of transmission and degree of virulence
- Direct contact
- less virulent
- Vector-borne
- highly virulent in human host; relatively benign in vector
- Greater ability to survive ouside host
- means more virulent
What is Tropism
- Tropism
- Pathogen must make contact with appropriate host tissue
- determined by specific cell surface receptors
- Pathogen must make contact with appropriate host tissue
- (note that transmission alone is not enough for infection to occur)
What are the five main modes of transmission
- Airborne (indirect)
- contact
- vehicle (indirect)
- vector borne
- vertical
inanimate materials or objects involved in pathogen transmission
Vehicles
Fomites
Common vehicle such as surgical instruments, bedding, and eating utensils
What is the difference between harborage transmission and biological transmission
- Both are types of internal transmission for vector-borne transmission
- Harborage transmission
- pathogen does not undergo changes within vector
- Biologic transmission
- pathogen undergoes changes within vector
Occurss when the unborn child aquires a pathogen form an infected mother
Vertical transmission
Examples of congential infection (born with infection)
- gonorrhea (especially in the eyes)
- herpes
- german measles
- toxoplasmosis
What is infectious dose 50
Dose that causes 50% of the host organisms to become infected
Infectious dose 50 for Bacillus anthracis in each of the 3 portals of entry
- ID50 through skin:
- is 10-50 endospores
- ID50 through inhalation:
- is 10,000 to 20,000 endospores
- ID50 through GI is 250,000-1,000,000 endospores
Cytopathology
- Can be used to observe cells in tissue culture for death rates rather than entire organisms
What are the two main factors of host susceptibility
- Defense mechanisms of host (innate and adapted/acquired immunity)
- Pathogenicity of pathogen
- (note that nutrition, genetic predisposition, and stress also play a role in host susceptibility to infection)
What are the portals of exit for a pathogen
- Respiratory tract
- coughing and sneezing
- Gastrointestinal tract
- Feces and saliva
- Genitourinary tract
- urine and vaginal secretions
- Skin
- Blood
- biting arthropods and needles or syringes
