5. Gram positive Cocci

Infectivity

§ability to infect

Pathogenicity

ability to cause disease

Virulence

ability to cause death

Gram positive cocci generally focuses on

Staphylococcus
Streptococcus
Enterococcus

Often times the inflammatory response caused by oral infection leads to

colonization of oral microbes in organs or tissues

Examples of staphylococci

include Staphylococcus aureus and Staphylococcus epidermidis

§Staphylococci grow in

clusters

Streptococci

grow in chains

replication axis: vertical

results in streptococcus and diplococcus

replication axis: horizontal

results in quad shaped

replication axis: diagonal

results in staphylococci

Staphylococci

gram positive cocci that produces CATALASE (+)

Oxygen of most staphylococci

Aerobic, facultative anaerobic

Streptococci oxygen

Most are facultative anaerobic, some anaerobic
CATALASE NEGATIVE

Staphylococci agar appearance

large white/yellow colonies

Staph aureus

golden/cream color colonies and are beta-hemolytic

Streptococci agar appearance

small white colonies, some hemolysis sometimes

S. aureus colonizes

anterior nares and/or skin

S. aureus is found on how many healthy inividuals

approximately 30% of healthy individuals

S. aureus is found in >80% of what type of patients

eczema/atopic dermatitis

What type of infection is S. aureus very commonly associated with

nosocomial infections due to its prevalence in healthcare settings.

How can you trace an infection/outbreak

DNA typing

S. aureus catalase

converts H₂O₂  —> H₂O + O₂

What enzyme associated with S. aureus helps it escape immune system

coagulase

S. aureus coagulase

Distinguishes S. aureus from other staphylococci based on ability to clot plasma

Is S. aureus encapsulated

yes, polysaccharide capsule inhibits phagocytosis

S. aureus penicillin effectivity

has beta-lactamase encoded via plasmid in most strains

S. aureus staphylokinase

enzyme that converts plasminogen to plasmin to inhibit phagocytosis by neutrophils (PMN)

S. aureus spreading factors

fibrinolysin, DNAse, hyaluronidase, phospholipase that help it dig deeper

S. aureus superoxide dismutase

enzyme that catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide, protecting the bacteria from phagocytes that release superoxide

S. aureus chemotaxis inhibitory protein

Competitively binds to neutrophil formyl peptide receptor and C5a receptor to inhibit neutrophil chemotaxis and reduce inflammation.

S. aureus resistance to lysozyme

Altered muramic acid in NAM which makes it harder to damage their cell walls

S. aureus exotoxin

Protein A

Impetigo

superficial skin infection commonly caused by S aureus

Cellulitis

infection of  dermal and subcutaneous connective tissue usually caused by S. aureus or Streptococcus species.

Overall skin diseases commonly associated with S. aureus

impetigo
cellulitis
folliculitis
Furuncle/boil
Carbuncle (masses of furuncles)

impetigo characterized by honey color crusts normally caused by S. aureus or Strep pyogenes

folliculitis

cellulitis

boil (large pimple)

carbuncle (fluster of furuncles)

Enterotoxin

targets intestines

When exotoxins are expressed systemically

they are superantigens that can activate large numbers of T cells.

When exotoxins are eaten

they cause bacterial intoxication (food poisoning)

Do gram positive pathogens make endotoxins

no they don’t have LPS

Which superantigens are associated with S. aureus

Toxic Shock Syndrome Toxin-1 (TSST-1) and Staphylococcal Enterotoxins

Superantigens

Activate large numbers of T cells (5-20%) expressing a particular set of V β genes causing MASSIVE CYTOKINE RELEASE

What is the consequence of massive cytokine release from superantigens

Fever (pyrogenic), organ failure, etc.
Also immune suppression

What does it mean that superantigens are antigen independent

can activate T cells without requiring specific recognition of antigen because it locks the TCR and MHC together

How do superantigens suppress the immune system

Superantigens can cause T cell anergy or apoptosis, leading to reduced T cell numbers and dysfunctional immune responses

S. aureus exotoxin: Protein A

binds to IgG Fc region, which locks it in the wrong direction, and hinders opsonization and phagocytosis

Staphylococcal food poisoning is caused by

Enterotoxin A which causes projectile vomiting

Enterotoxins directly affect the

intestinal epithelium

S. aureus: Toxic Shock Syndrome Toxin (TSST)

Pyrogenic exotoxin, enterotoxin B (superantigens) that can cause severe systemic effects such as shock and multi-organ failure.

TSS in males

usually from deep tissue infection after injury

TSS in females

High-absorbency tampon use (now rare)

S. aureus: cytotoxins a, b, d, g

Toxic for many blood cell, including RBC, WBC

S. aureus: exfoliatin A and B

splits desmosomes in epidermis
“Scalded skin syndrome”

Most common cause of osteomyelitis

due to S. aureus, particularly in adults, and is characterized by bone infection.

1 exception to S. aureus normally causing osteomyelitis

Osteomyelitis of mandible, which is more commonly cause by oral bacteria

S. aureus acute endocarditis

very severe and deadly infection from bacteremia originating from skin infection, surgery, or IV catheter

S. aureus septic emboli

embolism that can dislodge and spread through the body

S. aureus issue with treatment

most are resistant to penicillins due to production of penicillinase

Penicillinase

β-lactamase specific to penicillin

Drug of choice for S. aureus

Penicillinase-resistant penicillin (e.g. methicillin)

Methicillin-Resistant Staphyloccus aureus (MRSA)

now common due to production of PBP2a which prevents antibiotic from binding to transpeptidase

DOC for MRSA

Vancomycin (not a beta-lactam antibiotic)

MRSA nasal colonization

in 2% if healthy people

Majority of MRSA infections are

skin and soft tissue infections.

risk factors for MRSA colonization: hospital associated (HA)

–Recent hospitalization

–Prolonged hospital stay

–Residence in long-term care facility

risk factors for MRSA colonization: community associated (CA)

–Recent antibiotic therapy

–Athletes

–Daycare and school students,

–Military personnel in barracks

–Had surgery

–Medical devices implants

–Injection drug use, needle sharing

Treatment of MRSA skin infection

Incision and drainage if abscessed

Vancomycin resistant (VRSA)

now becoming more common, plasmid mediated

Is there any S. aureus resistance to 2nd line antibiotics

yes, linezolid reported in 2010

Staphylococcus epidermidis & other coagulase-negative staphylococci are found in

normal flora of skin and mucous membranes

S. epidermidis slime layer

prevents drying and attaches to tissues and foreign bodies

Most coagulase neg Staph infections are from

self flora

Treatment of S. epidermidis

needs antibiotic susceptibility testing to determine the appropriate antibiotic as resistance is common.

Zone of inhibition

is the area around an antibiotic disc where bacterial growth is inhibited, indicating the effectiveness of the antibiotic against a specific bacterium.

Most infections caused by streptococci have what type of hemolysis

are beta-hemolytic, indicating complete lysis of red blood cells.

Which strep is associated with alpha-hemolysis

S. viridans

How are streptococci classified

lancefield system

lancefield system

Classification of streptococci based on antigens on bacterial cell wall

Group A strep

Streptococcus pyogenes, skin & throat infections

Group B strep

Streptococcus agalactiae, neonatal meningitis

Which group strep is associated with beta-hemolysis

Both Group A (pyogenes) and Group B (agalactiae)

Non lancefield strep

lack lancefield carbohydrate antigens —> S. pneumoniae and viridans

S. pyogenes most important virulence factor

M protein

S. pyogenes: M protein

virulence factor that acts as a adhesin and destroys C3 convertase to inhibit opsonization and prevent phagocytosis of bacteria.

Properties of GAS M protein

anti-opsonic, antiphagocytic, adhesin

S. pyogenes F protein

adhesin that binds fibronectin

S. pyogenes capsule

virulence factor associated with evasion since its antiphagocytic

Streptococcal pyrogenic exotoxins (Spe)

acts as a superantigen to cause major cytokine storm, associated with S. pyogenes

S. pyogenes: Streptococcal pyrogenic exotoxins (Spe) is made from

phage (lysogenized strains)

Streptococcal pyrogenic exotoxins (Spe) are mostly associated with which strep

mostly S. pyogenes GAS

Spe exotoxins are structurally and functionally similar to

Staphylococcus aureus TSST-1 since they are both superantigens that cause cytokine storm

Hemolysins

extracellular toxins including Streptolysin O and S

GAS Streptolysin O

Binds to cholesterol in membranes, forms pores

GAS Streptolysin S

Responsible for β-hemolysis

GAS spreading factors

Hyaluronidase, streptokinase (dissolves blood clots), streptodornase (nuclease), DNAse, C5a peptidase