Microbiology > Lesson 3.6 - Staphylococcus aureus & MRSA > Flashcards

Lesson 3.6 - Staphylococcus aureus & MRSA Flashcards

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1
Q

Appearance/characteristics of S. aureus

A
  • Gram (+), cocus
  • Organized in clusters
  • Common in anterior nares, nasal membrane, nasopharynx, skin, perineum, GI tract & genital tract
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2
Q

In 2017, S. aureus incited _____ bloodstream infections with _______ associated deaths.

A
  • 119,247
  • 19,832
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3
Q

Define virulence factors

A

Expressed as a phenotype

Virulence is ability of an organism to cause disease

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4
Q

Host entry [S. aureus}

A
  • Hair follicle, scratch/cut, needle stic, surgery scars/sutures, respiratory & GI tract
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5
Q

How does S. aureus spread? What happens?

A
  • Spread via circulatory system, infect muscle, heart meninges, kidney, bone
  • Leads to pus, tissue necrosis, inflammation, blood clots
    • Supprative: pus forming
      • Dead neutrophils, macrophages, host cells, fluid

Major cause of nosocomial infections*

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6
Q

What does MSCRAAMS stand for? What is it?

A
  • Microbial Surface Components Recognizing Adhesive Matrix Molecules
    • ​​​Generic term used to describe adhesive proteins of S. aureus
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7
Q

What are the [3] types of MSCRAAMS?

A
  • Collagen adhesion
    • ​septic arthritis, osteomyelitis
  • Fibrinogen Binding Protien
    • ​attach to blood clots & injured tissue
  • Fibronectin Binding Protein
    • ​part of and attaches to extracellular matrix
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8
Q

What are types of toxins produced by S. aureus? (8)

A
  • All strains produce at least one of following
    • α (alpha) toxin
    • ß (beta) toxin
    • δ (delta) toxin
    • Leukotoxin γ
    • Panton-Valentine Leukocidin (PVL)
    • Exfoliation toxin
    • Enterotoxin
    • Super-antigen
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9
Q

α-(alpha) toxin

A

Lysis of RBC, monocytes, & platelets

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10
Q

β (beta) toxin

A

sphingomyelinase (degrades sphingomyelin)

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11
Q

δ (delta) toxin

A

small peptide w/ unk f(x)

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12
Q

Leukotoxin γ (gamma)

A

alters permeability of luekocytes’ membrane

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13
Q

Panton-Valentine Leukocidin (PVL)

A

specifically attakcs neutrophils

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14
Q

Exfoliation toxin

A

scalded skin syndrome; incites separates of skin layers

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15
Q

Enterotoxins

A
  • [6] diff types
    • Cause diarrhea & vomiting
    • Some withstand cooking
      • Response for S. ​-related food posioning
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16
Q

What are super-antigens?

A
  • Stimulate T-cells w/o usual antigen recognition process
    • Can interact w/ 1/5 of T-cells
      • Massive (non-specific) activation, cytokine release & systemic inflammation
      • Life-threatening
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17
Q

Describe Toxic Shock Syndrome Toxin No. 1 (TSST-1)

A
  • Super-antigen
    • Binds to MHC II receptor of APCs
  • Fever, diarrhea, vomiting, shock
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18
Q

What is involved w/ evasion of phagocytes? [S. aureus]

A
  • Coagulase
  • Protein A
  • Capsule production
  • Biofilm formation
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19
Q

What is coagulase?

A

Enzyme that catalyzes fibrinogen (soluble) to fibrin (insoluble) conversion; allows S. aureus to hide in clots

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20
Q

What is Protein A?

A
  • Cell wall protein that binds to Fc region of IgG
  • Prevents Abs acting as opsonins
  • Camouflage
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21
Q

What is involved with survival within phagocytes? [S. aureus]

A
  • Carotenoids
    • Golden yellow pigment
    • Detoxify O2- (reactive O) compounds
  • Catalase
    • Inactivates H2O2 made by neutrophils
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22
Q

What extracellular enzymes involved in assisting [S. aureus] in spreading?

A
  • Staphylokinase
    • Degrades fibrin
  • Hyaluronidase
    • Degrades hyaluronic acid (retains H2O in skin, joints, eyes)
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23
Q

Antibiotic Resistance Events [Timeline]

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A

Basically, resistance increased over time (evolved)

24
Q

______ was developed in the late 1950s as a replacement for penicillin.

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A

Methicillin; no longer used clinically

25
MRSA now stands for
Multiple Drug Resistant *S. aureus*
26
MSSA stands for
Methicillin sensitive *S. aureus*
27
Roughly ___ of healthy adults colonized by *Staphylococcus*
* 1/3; anterior nares * 1-2% healthy adults colonized by MRSA * 5-6% healthcare workers colonized by MRSA
28
What type of MRSA transmitted to patients via human hands?
* HA-MRSA: Healthcare-Associated MRSA * ***_U BETTER WASH UR MF HANDS W SOAP AND WATER OR ALCOHOL-BASED SANITIZER BC AT BEST 50% ADHERE TO IT CORRECTLY IN HEALTH FACILITIES_*** * Nurses have better hand hygiene than physicians
29
What is community-associated MRSA?
* Acquired by ppl who haven't been hospitalized w/in past year * Present at skin infections (pimples, boils) * Can survive 8 weeks on acrylic fingernails * 6 weeks on computer keyboards * 5 days on bed linen
30
Where are MRSA strains commonly isolated from?
Pigs, turkeys, cattle & horses; Jumped from humans to livestock and back - dogs and cats have it too
31
LA-MRSA stands for ...
Livestock-associated MRSA
32
VRSA stands for...
Vancomycin resistant *S. aureus*
33
What lead to the evolution of multi-drug resistant *S. aureus?*
* **Altered pencillin binding proteins** * **ß-lactamase (SBL, ESBL, MBL)**
34
Function of transglycosylases (Gram + cell wall)
Catalyze ß-1,4 glycosidic bonds
35
Function of transpeptidase (Gram + cell wall)
Catalyze bond b/t pentapeptide crosslink & D-alanine & removes terminal D-alanine from NAM
36
What happens to Gram + cell in presence of ß-lactam?
* ß-lactam bind irreversibly to transpeptidase active site * Transpeptidase catalyze bond b/t ß-lactam & D-ala * Reminiscient of D-ala-D-ala structure * Gram (+) cell wall can't survive osmotive pressure * BOOM!
37
What are Pencillin Binding Proteins (PBPs)?
* Enzymes involved in peptidoglycan biosynthesis * Bind penicillin & other ß-lactam antibiotics * Mutations in PBP genes lead to enzymes w/ low affinity for ß-lactam antibiotics (resistance)
38
What enzymes are involved in peptidoglycan biosynthesis?
* Penicillin Binding Proteins (PBPs) * Transpeptidases * cross-links peptidoglycan chains * Endopeptidases * hydrolyze peptide bonds in peptide (not terminal ones) * Carboxypeptidases * remove terminal D-ala from pentapeptide side chains of NAM (like a backup for transpeptidases)
39
What is PBP2a?
* Mutant protein (by HGT) w/ little-no affinity for ß-lactam antibiotics * MRSA strains have this
40
What is PBP2? What enzyme involved?
* **Wild type** sensitive to ß-lactams * Bifunctional enzyme * Transpeptidase & transglycosylase * Cross-links peptidoglycan chains & catalyze ß-1,4 glycosidic bonds b/t NAM & NAG * UnitProt: Q53729
41
What is the *S. aureus* mecA gene?
* Confers resistance to ALL ß-lactam antibiotics * Codes for PBP2a * Carried on mobile gene cassette * HGT!
42
*S. aureus* Resistance Cassette Features
* **mecA gene (resistance)** * **Casette chromosome recombinase (crr) genes** * Site-specific recombinases responsible for integration & cutting of cassette (transmitted by conjugation) * **Accessory genes & elements** * May or not be involved in resistance
43
There are how many versions of categories of SCCmec?
* **13 versions (I-XIII) & abt. 79 subcategories** * **​**size ranges 20-60 kb * Types I - IV document evolution of resistance
44
SCCmec I-X & XI
* **mecA & mecC** = PBP2a variants * **mecRI** = regulatory genes * **ccrA & ccrB** = specify site-specific recombinases * **J1, J2 & J3** = joining regions * **blaZ** = (ß-lactamase allele Z) hydrolze amide bonds Arrows on image indicates direction of transcription
45
What are ß-lactam antibiotics? What are its [4] categories?
* Cyclic amide * Inhibit bacteria from maintaining its cell wall = death * Categories: * **Penicillins** * **Cephalosporins** * **Carbapenems** * **Monobactams** (Aztreonam)
46
What are ß-lactamases? What are its [3] categories?
* Catalyze hydrolysis of amide bond in ß-lactam ring * Categories: * **Serine ß-lactamases (SBL)** * **Extended-spectrum ß-lactamases (ESBLs)** * **Metallo-ß-lactamases (MBL)**
47
What are Serine ß-lactamases (SBL)?
* _Confers resistance in some penicillins & cephalosporins_ * Active site serine facilitates hydrolysis of ß-lactam ring * **Nucleophilic attack** via serine * nucleophile replaces f(x) group w/in another nucleophile * bla genes on plasmids & chromosomes
48
What are Extended-spectrum ß-lactamases (ESBLs)?
* _Confer resistance to ALL penicillins, ALL cephalosporins, & monobactam (aztreonam)_ * **NOT cephamycins or carbapenems**
49
What can metallo-ß-lactamases (MBL) hydrolyze?
* Hydrolyze ALL ß-lactams * _Penicllins, cephalosporins, carbapenems singly & ß-lactamase inhibitors_ * Aztreonam (monobactam) not affected
50
How do metallo-ß-lactamases (MBL) work?
* Cleaves amide bond of ß-lactam ring via nucelophilic attack * OH- donates e- to carbonyl carbon * Stabilized by Zn1 & Zn2 * Genes ocated on chromosomes & mobile genetic elements * blaMBL commonly found on integrons, integrated into transponsons; also on plasmids & chromosomes
51
What are ß-lactamase inhibitors?
* Have a ß-lactam ring, but weak antimicrobial activity * Bind irreversibily to ß-lactamase active site; permanently inactivates enzyme * Competitive inhibition * Co-administered w/ antibiotic = lowers MIC
52
What is Amoxicillin & Clavulanic Acid?
* Amoxicillin = ß-lactam antibiotic * Clavulanic Acid = ß-lactamase inhibitor * Weak if alone * Combination = tablets or oral suspension * ie. AugmentinTM * Greater effect (refer to image)
53
US MRSA Trends
* Declining Hospital-onset MRSA & MSSA * Improved practices * Increasing community-onset MSSA, stable MRSA
54
MRSA Infection by State (Overview)
* Most: DC at 20.4 per 100,000 * Least: Wyoming at 1.26 per 100,000
55
Factors associated w/ MRSA
* Income * Below poverty line = less spacious homes = ^ MRSA * Race * Black individuals (insection of education & healthcare access) * Education * Lower education = ^ MRSA * Antibiotic Prescriptions * Non-ß-lactams use = ^ MRSA * Lincosamides (clindamycin), glycopeptides (vancomycin) & sulfonamids (sulfamethoxazole/trimethoprim)
56
Global MRSA trends
* Lower MRSA * Better government, public infrastructure, healthcare investment * Higher MRSA * Poor gov, public infrastructure, & more private than public healthcare
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