Bacterial Pathogenesis Flashcards
Every human is colonised,.
by numerous bacterium
A pathogen is
an organism that cause infection in individuals with normal host defences
A commensal is…
an organism that is found normally on those parts of the body that they are exposed to, or communicate with, the external environment
An opportunist is where
an organism that can cause infection in individuals with abnormal host defences
Koch’s postulates states….
- pathogen must be present in every case of disease
- Pathogen must be isolated from the diseased hose and grown in pure culture
- the specific disease must be reproduced when a pure culture of the pathogen is inoculated into a healthy host
- pathogen must be recoverable from the experimentally affected host
Disease can arise in several different ways…
- some bacteria are entirely adpated to the pathogenic way of life in humans. They are never part of the normal flora but may cause subclinical infection.
- Some bacteria which are part of the normal flora acquire extra virulence factors making them pathogenic
3.
Changes in normal flora
- changes in normal physiology and development
- when antibiotics select for a resistant flora
- new organisms may be acquired.
Pathogens can transmit via
oral-oral, fecal-oral, blood and sexual contact, Animals, vectors, environment and food
Microbial pathogenicity factors are…
examples of PAMP’s
bacteria need
cell wall associated proteins in order to bind to host cells
Gram positive proteins
have surface proteins which allow the attachment of the bacteria to the cell of the host
Gram negative bacteria use pili and fimbriae to
bind to host cells
Bacterial flagellae
confer motility to many bacteria and it is another example of a PAMP
Bacteria also needs to get something to eat
This occurs via the invasion of host cells. This is an example of a DAMP
Toxins produce different bacteria
- Exotoxins, which is any toxin that is actively secreted by a bacterium in the environment
- endotoxin (such as Lipopolysaccharides in gram negative bacteria)
- enterotoxin
Exotoxins can act like
proteases, .and other degrading enzymes
Type III secretion system
are needed for the delivery of toxins
for a bacteria to protect itself, it could…
make a polysaccharide capsule, slime, and biolfilm. LPS can be modulated by bacteria to cause cytokine overstimulation and lead to septic shock. Outer membrane proteins could affect antimicrobial peptides and complement factors
Bacterial adaptation is
adapting to changing and new environments
Microbe- host interactions include
- preventing opsonization
- toxin secretion can paralyze the host’s defences
- Disruption of mucosal integrity
- microbial recognition and host responses
- chemokine production
- inspired by modification of PAMP or interference with intracellular signalling or cell trafficking.
Regulatory networks include
Two component systems such as LPS modification, Quorum sensing, and Efflux pumps (drug resistance)
SIGNAL -
Environmental change - signalling molecule
Regulator
usually specific DNA binding protein - binds in control region
Regulon
Group of genes controlled by a common regulator
Bacterial Regulons include
- catabolite suppression
- DNA supercoiling
- SOS response to DNA damage
2CS
Stimulus response mechanism - signal transduction….
When there is a low magnesium concentration in a macrophage
salmonella can hijack the low MG conditions which can modulate transcription and expression of genes
When a plant detects low calcium,
an immune response can be regulated to protect itself against a microbe
A biofilm is a…
structured community of bacterial cells enclosed in a self produced polymeric matrix and adherent to an inert or living surface. Biofilm formation is considered to be a pathogenic trait.
Quorum sensing is
key to biofilm formation. This mechanism of biofilm formation is cell density dependent. Low molecule weight compounds autoinducers.
QS signal molecules include
PQS, HHQ, HHQNQ
Efflux pumps are
-encoded by all bacteria, regardless of antibiotic load or environment
- regulated by chromosomal factors
One example of such pumps are the RND pumps.
The regulation of efflux pumps can be
local repressors, global regulators (2 Component systems, AHL signalling systems)
AcrR acts as a
local repressor of the efflux pump
Secretion systems facilitate
intra and intercellular communications- Necessary for export of nutrients and protection
against host-mediated response
The type of secretion system depend on
cell wall structure
- Gram positive - transportation of protein through a single membrane
– Gram negative-involves multi-subunit structures-inject
toxin directly into host.
Sec & TAT (general secretory pathway)
• Used to transport proteins across cytoplasmic membrane. • Highly conserved • Proteins transported remain within the cell i.e. periplasm or IM. • Gram-Neg can transport proteins using secretion systems. • Common elements but translocation of proteins is different.
Gram positive need a facilitator protein for its secretory pathway called
SecA2
The SecA2 Secretion pathway…
Sec secretion pathway
– Conserved mechanism of protein export
– Used by Staphylococcus and Streptococcus species
to function as adhesins
Sortases
– Covalently attached proteins on cell wall, survival
during infection
– Embedded in Gram-positive cell wall
– SrtA recognises N-terminal signal peptide
– Eg. Pili
The difference between sec and tat is
sec transports unfolded proteins and tat transports folded proteins
