Download File

Staphylococcus aureus
An introduction to the genetic
features of MRSA
What is a pathogen?
• A pathogen is a disease causing agent
Bacteria
Fungus
Protozoa
Virus
Images: Janice Carr; CDC/Dr. Godon Roberstad; Wellcome Images; Anna Tanczos, Wellcome Images
Question
Can you name a disease caused by
bacteria?
Structure of bacteria
Staphylococcus aureus
• Widespread bacteria:
– Natural flora of the skin of 30% of
the population
• Versatile pathogen associated
with a wide range of diseases:
–
–
–
–
Image: Sharon Peacock, Oxford University
Minor wound infections
Food poisoning
Toxic shock syndrome
Heart infections
How does S. aureus cause disease?
• Bacteria have a range of molecular “weapons”
to help them invade a host and evade
detection.
• What do you think these “weapons” are?
The S. aureus arsenal
Fibronectin binding protein
Collagen binding protein
Toxins
Hemolysins
Leukocidins
Enterotoxins
Exfoliative toxins
Toxic shock syndrome toxin
Clumping factor
S. aureus
Protein A
Elastin binding protein
Matrix adhesion factor
Surface proteins
Enzymes
Lipases
Esterases
Nucleases
Coagulases
Phospholipase C
Extracellular proteins
What is a surface protein?
• Surface proteins are found on the outside of S.
aureus.
• They enable it to attach to host cells aiding
tissue invasion and colonisation.
• Examples:
– Elastin binding protein
– Collagen binding protein
What is a toxin?
• A protein that has the ability to damage
specific cells and cellular components.
Q. Can anyone think of a disease or syndrome
caused by bacterial toxins?
Staphylococcal Scalded Skin Syndrome
• SSSS is an exfoliative dermatitis,
a condition where skin flakes or
peels off.
• Causal Factor : Exfoliative toxins
A and B.
• Can vary in severity ranging
from a few localised blisters to
generalised exfoliation covering
almost the entire body.
Images: CDC
Toxic Shock Syndrome
• Symptoms: sudden onset of
fever, chills, vomiting,
diarrhoea, muscle aches and
rash. Can lead to hypotension
and anaphylactic shock which
can lead to organ failure.
• Causal factor: S. aureus toxic
shock syndrome toxin.
• Associated with tampon use
and also as a complication of
skin abscesses or surgery.
Strawberry tongue symptom of TSS
Image: CDC
What is an enzyme?
• Enzymes break down organic compounds of
cells and tissues, allowing the bacteria to
absorb nutrients and also to spread through
body tissues.
• Examples:
– Protease
– Coagulase
– Lipase
How do you treat S. aureus infections?
• Diseases caused by S. aureus are usually
treated with bactericidal antibiotics and the
patient is normally free of pathogenic bacteria
within a month.
• Antibiotics include:
– penicillin
– oxacillin
– nafcillin
Image: Bmramon/wikimedia commons
Superbugs & antibiotic resistance
• Methicillin resistant
Staphylococcus aureus (MRSA)
is termed a “superbug”.
• Common cause of hospital
acquired infection.
• Hospital-acquired MRSA
infections lead to:
– prolonged hospital stay
– increased costs to NHS
How does resistance occur?
• Use of antibiotics creates a
selective pressure.
• Only bacteria with genes
that confer resistance can
survive a treatment of
antibiotics.
• Eventually resistant
bacteria can make up the
majority of the population.
Population after
Before
antibiotics
Add
antibiotics
antibiotics
Genetic diversity of bacteria
• Bacteria are under continuous selection
pressure and are constantly evolving to adapt
to changes in their environment.
• How?
– Mutations occur within the genome during DNA
copying and because of damage to DNA which
confer a selective advantage.
– Horizontal gene transfer (direct exchange of genes
between individual bacteria).
Horizontal transfer
• New antibiotic genes can be acquired via
horizontal transfer or conjugation.
Images: Genome Research Limited
Viewing diversity
S. aureus comparative genomics
8325
USA300
COL
Mu50
N315
MW2
MSSA476
MRSA252
RF122
0 Mb
1.0 Mb
Staphylococcal cassette chromosome (SCC) element
Genomic islands shared with other S. aureus strains
Pathogenicity islands
2.0 Mb
Integrated plasmid
Prophage
Transposon
Tn916-like element
3.0 Mb