MRSA

Question 1

What are S.aureus?

Answer 1

Gram-positive cocci
Commensal bacteria colonising mammals and birds

Question 2

Describe S.aureus

Answer 2

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

Question 3

What do S.aureus colonies look like?

Answer 3

Golden on blood agar

Question 4

What does S.aureus produce?

Answer 4

Dozens of virulence factors - toxins, immune evasion mechanisms, bind to host tissues, etc

Question 5

What selective media is used to diagnose S.aureus?

Answer 5

Mannitol Salt agar (MSA)

Question 6

What other bacteria can be cultured on MSA?

Answer 6

Staph epidermidis
Micrococcus luteus

Question 7

What are Methicillin resistant staphylococcus aureus?

Answer 7

S.aureus that carry mecA gene on SCCmec mobile genetic element

Question 8

What are MRSA resistant to?

Answer 8

All beta-lactam antibiotics
Inc. flucloxacillin, carbepenems, cephalosporins

Question 9

Why are beta lactams best to use?

Answer 9

Inexpensive
Orally administered
Few side effects

Question 10

What is the main class of drug used to treat and prevent MRSA?

Answer 10

Glycopeptides

Question 11

How does MRSA impact healthcare?

Answer 11

MRSA infection incidence adds to S.aureus burden
No vaccine for S.aureus or MRSA
Patients with MRSA infection treated with inferior antibiotics

Question 12

What happens if MRSA in the hospital is common?

Answer 12

Beta lactams cannot be used for prophylaxis or empirical therapy

Question 13

What are the reservoirs of MRSA?

Answer 13

Normally live in/on host predominantly in nose, throat, armpit and groin
Each host niche is colonised by ecosystems of microbes (microbiome)

Question 14

What do colonising bacteria act as?

Answer 14

Often they are the reservoir of infecting bacteria particularly in immunocompromised hosts
>80% of patients become infected with their own S. aureus colonising bacteria

Question 15

What are the types of MRSA?

Answer 15

Hospital associated
Community associated
Livestock associated

Question 16

How do S.aureus vary?

Answer 16

Mobile genetic elements

Question 17

What define lineages/clonal complexes?

Answer 17

Unique combinations of hundreds of genes, especially surface proteins and their regulators

Question 18

What is the S-aureus gene structure?

Answer 18

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

Question 19

What influences invasive disease from S.aureus?

Answer 19

Host factors

Question 20

What are the differences between human and animal isolates of S.aureus?

Answer 20

Bovine isolates belong to unique lineages
Horse isolates belong to either bovine or human lineages

Question 21

What are the human specific S.aureus genes?

Answer 21

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

Question 22

What can happen if MGEs are transferred?

Answer 22

New DNA can lead to a strain with enhanced virulence or resistance

Question 23

What is encoded on MGEs?

Answer 23

Most of the AMRs, toxins and host-specificity factors

Question 24

Name the MGEs of S. aureus

Answer 24

Staphylococcal cassette chromosomes (SCCs)
Bacteriphage
S. aureus pathogenicity islands (SaPI)
Plasmids
Transposons

Question 25

What does SCC encode?

Answer 25

Resistance to methicillin, kanamycin etc. Gene for mucoid capsule

Question 26

What does the bacteriophage encode?

Answer 26

Panton-Valentine leukocidin Enterotoxin A Exfoliative toxin

Question 27

What does SaPI encode?

Answer 27

Enterotoxins B/C Toxic shock toxin

Question 28

What do plasmids encode?

Answer 28

Resistance to b-lactams, tetracyclines, aminoglycosides, macrolides, fusidic acid, heavy metals Exfoliative toxin

Question 29

What do transposons encode?

Answer 29

Resistance to macrolides, b-lactams, vancomycin

Question 30

What have successful antimicrobial resistant HA-MRSA accumulated on MGEs?

Answer 30

mecA on SCCmec Phi3 scn, chp, sak Bacteriophage vanA on conjugative plasmid/transposon from Enterococci (vancomycin resistance)

Question 31

Describe CA-MRSA

Answer 31

Severe skin and soft tissue infection in healthy people Outbreaks in schools, sports teams, military, prisons (close contact environments) Prevalent in US and Asia

Question 32

What is the marker of CA-MRSA?

Answer 32

Panton Valentine leukocidin (PVL) toxin gene carried on bacteriophage

Question 33

What have successful AMR CA-MRSA accumulated on MGEs?

Answer 33

mecA on SCCmec phi3 scn, chp, sak Bacteriophage Virulence/PVL toxin on bacteriophage

Question 34

Describe LA-MRSA

Answer 34

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

Question 35

What have successful AMR LA-MRSA accumulated on MGEs?

Answer 35

mecA on SCCmec Tetracycline resistance on plasmids/transposons

Question 36

What is the mechanism of gene transfer?

Answer 36

Generalised transduction via endogenous bacteriophage

Question 37

What blocks horizontal transfer?

Answer 37

Restriction modification