Staphylococcus aureus An introduction to the genetic features of MRSA
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
Question Can you name a disease caused by bacteria?
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
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 Toxins Hemolysins Leukocidins Enterotoxins Exfoliative toxins Toxic shock syndrome toxin Fibronectin binding protein S. aureus Collagen binding protein Clumping factor Protein A Enzymes Lipases Esterases Nucleases Coagulases Phospholipase C Elastin binding protein Matrix adhesion factor Surface proteins Extracellular proteins
What is a surface protein? • Surface proteins are found on the outside of S. aureus. • Theyenable 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 exfoliationcovering 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 antibiotics Before antibiotics Add 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
8325 USA300 COL Mu50 N315 MW2 MSSA476 MRSA252 RF122 0 Mb 1.0 Mb 2.0 Mb 3.0 Mb Integrated plasmid Prophage Transposon Tn916-like element Staphylococcal cassette chromosome (SCC) element Genomic islands shared with other S. aureus strains Pathogenicity islands Viewing diversityS. aureus comparative genomics
Activity: MRSA gene hunt • Identify and classify genes from the genomes of two S. aureus strains. • MSSA 476: Methicillin susceptible strain but resistant to penicillin and fusidic acid (commonly used antibiotics). • MRSA MW2: Extremely virulent and resistant to methicillin.
Gene ID cards Gene ID: gene name Description of the protein product and function Strain of bacteria
Complete your worksheet Write role or function of protein here Write protein product here
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
Discussion point • MRSA can be treated with vancomycin. However the first vancomycin-resistant strains were discovered in 2003. • What are the implications of this?