03_pathogenesis-virulence

pathogenesis

capacity of a microbe to cause damage to the host

viruelence

referes to the degree of damage caused by the microbe

-> continuum: avirulent -> … -> virulent -> … -> highly virulent

a product made by the organism that contributes to overall virulence

• capsules: protection against host defence

• flagella: movement (towards nutrients)

• pili: attachement to other cell walls (exchange of genetic material between one another)

• spores: inactive forms of bacteria that can survive for years

• toxins: released products which can dysregulate critical cellular processes or improve capacity of proteins to invade tissue

• sideropheres: iron-binding factos, competition with host for iron

• other adhesion, colonisation and invasion factors

quantification using controlled experiments with lab animals (i. s. c. human studies)

-> infective dose widely vary and depending

ID50 - median infectious dose

# of pathogen cells to active infect 50 % of inoculated animals

LD50 - median lethal dose

# of pathogen cells to kill 50 % of infected animals

• S. enterica serovar Typhimurium

• EHEC

• EIEC

• EPEC

• ETEC

• Salmonella enterica serovar Typhi

• Shigella dysenteriae

• Vibrio cholerae

• V. parahemolyticus

primary pathogen

causes disease in host regardless of host’s resident microbiota or immune system

opportunistic pathogen

only causes disease in situations that compromise host’s defenses (e. g. body’s protective barriers, immune systen, normal microbiota)

higher risk individuals

• very young

• elderly

• pregnant women

• chemotherapy patients

• immunodeficiency’s

• recovering from surgery

• breach of protective barriers (severe wounds/burn)

primary - EHEC

production of Shiga toxin -> inhabitation of protein synthesis -> bloody diarrhea, inflammation, renal failure

opportunistic - Staphylococcus epidermidis

member of normal skin microbiota -> grow in biofilms on catheters, implants which are inserted into the body during surgical procedures -> serious infections such as edocarditis, production of viruelence factors promoting persistence of such infections

disease transmitted to human from animals

• EHEC

• Black plague

• Camphylobacter jejuni

1. Exposure

   encounter with potential pathogen, gain access into host tissue through so-called portal of entry

2. Adhesion

   attachment of pathogenic microbes to cells of body using adhesions

3. Invasion

   dissemination of a pathogen throughout local tissue/body, may produce exoenzymes/toxins (colonise & damage host tissue and virulence factors for own protection against immune system defenses of host)

4. Infection

   successful multiplication => infection

clostridiales difficile

-> antibiotic therapy targeting primary pathogen causing collateral damage to normal microbiota -> opening for opportunistic pathogens

acquisition of genes encoding virulence factors

-> evolution of non-pathogenic bacterial species into genetically related but pathogenic species

=> may encoded in cDNA, plasmids, bacteriophage DNA, transposons (plasmid/bacterial chromosome)

• toxin production

• increased adhesion & toxin production

• increased adhesion

• increased adhesion & membrane modification

insertion of foreign DNA into bacterial chromosomes

-> pathogenicity island := larger inserts

=> frequently encode virulence associated traits

Salmonella pathogenicity island 1 - encodes Type 3 secretion system (key to host cell attachment)