MRSA Flashcards
What are S.aureus?
Gram-positive cocci
Commensal bacteria colonising mammals and birds
Describe S.aureus
25% of healthy humans carry S.aureus in their nose
Common cause of minor infections not requiring antibiotic treatment
Common cause of hospital-associated infection in immunocompromised patients
What do S.aureus colonies look like?
Golden on blood agar
What does S.aureus produce?
Dozens of virulence factors - toxins, immune evasion mechanisms, bind to host tissues, etc
What selective media is used to diagnose S.aureus?
Mannitol Salt agar (MSA)
What other bacteria can be cultured on MSA?
Staph epidermidis
Micrococcus luteus
What are Methicillin resistant staphylococcus aureus?
S.aureus that carry mecA gene on SCCmec mobile genetic element
What are MRSA resistant to?
All beta-lactam antibiotics
Inc. flucloxacillin, carbepenems, cephalosporins
Why are beta lactams best to use?
Inexpensive
Orally administered
Few side effects
What is the main class of drug used to treat and prevent MRSA?
Glycopeptides
How does MRSA impact healthcare?
MRSA infection incidence adds to S.aureus burden
No vaccine for S.aureus or MRSA
Patients with MRSA infection treated with inferior antibiotics
What happens if MRSA in the hospital is common?
Beta lactams cannot be used for prophylaxis or empirical therapy
What are the reservoirs of MRSA?
Normally live in/on host predominantly in nose, throat, armpit and groin
Each host niche is colonised by ecosystems of microbes (microbiome)
What do colonising bacteria act as?
Often they are the reservoir of infecting bacteria particularly in immunocompromised hosts
>80% of patients become infected with their own S. aureus colonising bacteria
What are the types of MRSA?
Hospital associated
Community associated
Livestock associated
How do S.aureus vary?
Mobile genetic elements
What define lineages/clonal complexes?
Unique combinations of hundreds of genes, especially surface proteins and their regulators
What is the S-aureus gene structure?
Core - found in all strains, >97% conserved, gene order
Core variable - define lineages, widely distibuted
Mobile genetic elements - inc many virulence factors, host adaptation factors and antimicrobial resistance genes
What influences invasive disease from S.aureus?
Host factors
What are the differences between human and animal isolates of S.aureus?
Bovine isolates belong to unique lineages
Horse isolates belong to either bovine or human lineages
What are the human specific S.aureus genes?
scn - complement inhib protein, human specific
chip - chemotaxis inhib protein, human specific
sak - staphylokinase, plasminogen activation and invasive spread, human specifc
sea - enterotoxin A, food poisoning
What can happen if MGEs are transferred?
New DNA can lead to a strain with enhanced virulence or resistance
What is encoded on MGEs?
Most of the AMRs, toxins and host-specificity factors
Name the MGEs of S. aureus
Staphylococcal cassette chromosomes (SCCs)
Bacteriphage
S. aureus pathogenicity islands (SaPI)
Plasmids
Transposons
What does SCC encode?
Resistance to methicillin, kanamycin etc.
Gene for mucoid capsule
What does the bacteriophage encode?
Panton-Valentine leukocidin
Enterotoxin A
Exfoliative toxin
What does SaPI encode?
Enterotoxins B/C
Toxic shock toxin
What do plasmids encode?
Resistance to b-lactams, tetracyclines, aminoglycosides, macrolides, fusidic acid, heavy metals
Exfoliative toxin
What do transposons encode?
Resistance to macrolides, b-lactams, vancomycin
What have successful antimicrobial resistant HA-MRSA accumulated on MGEs?
mecA on SCCmec
Phi3 scn, chp, sak
Bacteriophage
vanA on conjugative plasmid/transposon from Enterococci (vancomycin resistance)
Describe CA-MRSA
Severe skin and soft tissue infection in healthy people
Outbreaks in schools, sports teams, military, prisons (close contact environments)
Prevalent in US and Asia
What is the marker of CA-MRSA?
Panton Valentine leukocidin (PVL) toxin gene carried on bacteriophage
What have successful AMR CA-MRSA accumulated on MGEs?
mecA on SCCmec
phi3 scn, chp, sak
Bacteriophage
Virulence/PVL toxin on bacteriophage
Describe LA-MRSA
Pig farms have become heavily colonised with LA-MRSA of lineage CC398
Humans that come into contact with these farms become colonised
Small proportion of humans become infected with their colonising isolates
What have successful AMR LA-MRSA accumulated on MGEs?
mecA on SCCmec
Tetracycline resistance on plasmids/transposons
What is the mechanism of gene transfer?
Generalised transduction via endogenous bacteriophage
What blocks horizontal transfer?
Restriction modification
