Staphylococcus aureus

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Staphylococcus aureus

• An introduction to the genetic features of MRSA

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What is a pathogen?

• A pathogen is a disease causing agent

Fungus
Bacteria
Protozoa
Virus
Images Janice Carr CDC/Dr. Godon Roberstad
Wellcome Images Anna Tanczos, Wellcome Images
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Question
Can you name a disease caused by bacteria?
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Structure of bacteria
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Staphylococcus aureus

• Widespread bacteria
• Natural flora of the skin of 30 of the
  population
• Versatile pathogen associated with a wide range
  of diseases
• Minor wound infections
• Food poisoning
• Toxic shock syndrome
• Heart infections

Image Sharon Peacock, Oxford University
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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?

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The S. aureus arsenal
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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

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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?

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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
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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
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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

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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
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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

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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 antibiotics
Before antibiotics
Add antibiotics
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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).

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Horizontal transfer

• New antibiotic genes can be acquired via
  horizontal transfer or conjugation.

Images Genome Research Limited
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Viewing diversityS. aureus comparative genomics
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Activity MRSA gene hunt

• Compare the genomes of two S. aureus strains.
• MSSA 476 Methicillin sensitive strain but
  resistant to penicillin and fusidic acid
  (commonly used antibiotics).
• MRSA MW2 Extremely virulent and resistant to
  methicillin.

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The genome browser
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Exploring genes
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Complete your worksheet
?
Write role or function of protein here
Write protein product here
?
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Answers
Gene Protein product Function MSSA 476 MRSA MW2 Classification
ccrA ccrB Cassette chromosome recombinase A B Allows new chunks, or cassettes of DNA to be inserted into the bacterial genome. ? ? Mobile genetic element
ear Enterotoxin B Attacks cell membranes which can lead to the cell bursting and dying as a result. ? Toxin
int (region 3) Intergrase Helps insert DNA copied from viral RNA or DNA into the bacterial genome. ? Mobile genetic element
fusB1 Fusidic acid resistance protein Blocks the action of fusidic acid making the bacteria resistant to common antibiotic skin creams and ointments. ? Antibiotic resistance
hsdR, hsdS hsdM Restriction modification enzymes Acts as a barrier against free-for-all horizontal transfer of DNA protecting the bacterias genome from invading fragments of DNA which could weaken it. ? Enzyme
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Answers
Gene Protein product Function MSSA 476 MRSA MW2 Classification
orfX Surface protein / gene insertion site A surface protein which marks the sites on the genome where mobile genetic cassettes can insert themselves. ? ? Surface protein
lukS lukF Panton-Valentine leukocidine chain precursors S F Part of the Panton-Valentine leukocidin complex. When secreted they combine to form a ring with a hole in the middle, within the membrane of target cells. This causes the contents of the cell to leak out and the cell to die. ? Toxin
mecA Penicillin binding protein Blocks penicillin-based antibiotics which stop synthesis of the bacterial cell wall to prevent growth and division. ? Antibiotic resistance
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Answers
Gene Protein product Function MSSA 476 MRSA MW2 Classification
sec4 Enterotoxin type c precursor A precursor to an enterotoxin. It has to be modified by another enzyme to become an active toxin. Once activated the toxin can damage cells in the gut which leads to symptoms such as diarrhoea. ? Toxin
sel2 Enterotoxin L A type of superantigen capable of causing a variety of symptoms by destroying the hosts cells. It stimulates the body to produce a large number of T immune cells, which damage healthy tissues around or near the area infected with S. aureus. This can cause extensive damage to tissues and major organs sending the body into shock. ? Toxin

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How similar are the two genomes?
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Summary
Antibiotic
Enzyme
Surface protein
Toxin
Mobile genetic
resistance
element
fusB1
hsdR
,
hsdS

orfX
ear
ccrA

ccrB
hsdM
mecA
lukS

lukF
int
sec4
sel2
Key MSSA 476 only MRSA MW2 only Both strains
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Discussion point

• MRSA can be treated with vancomycin. However the
  first vancomycin-resistant strains were
  discovered in 2003.
• What are the implications of this?