Pathogen Host Attack Flashcards
Learning Objectives
- general strategies that bacteria use to maintain an environmental reservoir (transmission)
-
molecular Koch’s postulates
3.** five** common steps by which bacteria cause disease - some virulence factors that are used by bacterial pathogens to cause disease (i.e. motility organelles like pili and flagella, toxins)
- how to set up an experiment showing that certain genes or proteins promote virulence
Why must bacteria maintain a reservoir?
because most pathogens spend extended periods of time in the external environment and many do not move from host to host
Major issues encountered by bacteria in the environment
- availability of essential nutrients
- lack of adherence sites or niches similar to host
- exposure to noxious chemicals/predator
- exposure to sunlight and extreme weather (UV radiation, desiccation, and thermal shifts)
What are some bacterial survival strategies?
- endosporulation (Gram +)
- desiccation resistance (Gram -)
- metabolic versatility (ability to use inorganic molecules for metabolism)
- dormancy (complete arrest of metabolism)
- genome plasticity (rearranging genes)
- colonize other hosts
- motility and chemotaxis
- alter membrane properties (different lipid composition of membranef - Gram -)
- xenobiotic efflux (export of foreign chemical substances)
-** biofilm formation**
Biofilm formation
viewed as developmental and social process that’s functionally analogous to multicellular differentiation
interactions may involve single or multiple species of microorganisms living in a metabolically integrated consortium (association)
this is only ONE of many ways microbes engage in social behaviours
Biofilm matrix polymers
matrix polymers made by bacterial polysaccharides and host matrix proteins = extra tough
i.e. Hyaluronin - host-derived extracellular matrix protein
polymers self assemble into liquid crystals, physical and chemical properties make biofilm resistant
Molecular Koch’s postulates
proof that a gene product is an essential virulence factor
1. pathogenic trait should be associated with pathogenic species of the genus, species or strain
2. inactivation of the gene associated with the pathogenic trait should result in the loss of pathogenicity/virulence
3. reversion or allelic replacement of the mutated gene should restore pathogenicity > complementation analysis (complementation - knock out gene to determine virulence of a specific gene)
How do we evaluate virulence factors?
compare the ability of WT and mutant bacteria to survive in a host and cause disease
1. dilute bacteria to known concentration
2. infect host (assess success of initial inoculation)
3. allow animals to get sick (WT, may take days)
4. harvest organs and assess bacterial growth and pathology
mutant bacteria may be impaired for survival (gene knocked out is related to virulence)
animals infected with mutants may NOT show certain signs of illness (i.e. histological scarring, weightloss, behavioural indicator,…)
What are the** five common steps** in bacterial infections?
- entry into host body for colonization
- evasion of host defense
- obtain nutrients, multiply to significant numbers and spread
- damage the host and produce disease
- transmission from infected to susceptible host
Where can pathogens enter the human body?
no known bacteria can penetrate human skin
entry occurs via wounds, burns, insect bites, ingestion of tainted food, the eye, inflammation, genitourinary tract
often requires attachment
migration to a niche (molecular tropism such as receptor mediated endocytosis for intracellular infection)
Flagella
long, helical structures extending outward from the cell surface (up to 20 micrometers)
polymers of flagellin protein
evolutionarily conserved (important for immunity)
mediates movement in fluid and attachment and penetration into cell
number and arrangement varies among species, different distribution along cell works well in different scenarios
Motility, Taxis and Sensing
motility is often directed by the ability to sense
i.e. sensing chemicals (chemotaxis), light (phototaxis), oxygen (aerotaxis), or magnetic fields (magnetotaxis)
sensing is followed by directional swimmig towards/away from the signals sensed
What must pathogens do after access into the body?
- bacteria often bind to specific cell types to gain entry into target tissue or remain in a niche
- once get past initial barrier (mucin), bacteria must remain in place without being dislodged (via coughing, peristalsis, swallowing, urination)
- once bypassed dermal layers/mucin, bacteria must survive other host innate immune system
Lamina propria
refers to the thin layer of loose connective tissue underneath the epithelial cells, can be a site of infection
Mucin
mucus: mesh of [glyco]proteins and polysaccharide
expelled by globet cells
act as a lubricant that also traps bactreria to prevent microbes from accessing/binding to the first layer of cells
is non-uniform (patchy)
Host and tissue tropism
refers to how viruses/pathogens have evolved to preferentially target specific host species, specific tissues, or specific cell types within the host
tropism is driven by molecular interactions between pathogen and host (i.e. adhesion to ligands on the bacterium and receptors on host)
Biofilm
dense, multiorgasimal layers of bacterial communities attached to a surface, mediated by polysaccharide slime and bacteria self-organize into micro-colonies in the biofilm
protects against: antibiotics, disinfectants, phagocytic attack, and resistance to external factors
Adherence
thought to be an essential first step in initiating disease
strategies for adhesion: flagella, pili, fimbriae, afrimbrial adhesins
Antimicrobial peptides
small proteins/peptides secreted by the host and have diverse inhibitory effects against pathogens/viruses (i.e. cause cell lysis, prevent DNA replication,…)
How do bateria bypass antimicrobial peptides secreted by the host?
secreting peptidases (enzymes that cleave proteins/peptides)
synthesizing capsular polysaccharide layers (limit diffusion of antimicrobial peptides into the cytosol)
lipopolysaccharide binding and modification (prevent recognition by the immune system)
Defensins
a type of antimicrobial peptide and is part of the innate immune system
work by disrupting bacterial cytoplasmic membrane (cause cell lysis)
have a positive charge that is critical for their function - which is binding to (negatively charged) DNA to prevent transcription and translation of bacterial chromosome
Nutritional immunity
host mechanisms that limits and restricts specific nutrients that are essential for growth
i.e. Fe is essential for all bacteria as enzyme cofactors. 80% of host iron is sequestered in hemoglobin and unavailable for bacterial usage
How do some bacteria overcome nutritional immunity?
some bacteria evolved to not use iron as an essential nutrient (i.e. B. burgdoferi uses Mn)
acquire sequestered iron (i.e. the evolution of multiple pathways such as siderophores to steal iron from proteins like hemoglobin)
Siderophores
low molecular weight compounds that chelate Fe
their binding afinity to Fe is very high compared to host = steal Fe from host proteins
