1. Gram-Positive Cocci Part 6-A
(First Semester )

2. Staphylococci and Streptococci
Gram-Positive Cocci
Staphylococci and Streptococci
Single cell: Coccus (spherical), Gram-positive
Cellular arrangement:
1- Staphylococci: Grape-like clusters
2- Streptococci : Chains (two or more)

4. Staphylococci: General features:
Spherical Gram-positive cocci that are arranged in grape-like clusters
Catalase positive
Non motile
Facultative anaerobic bacteria
Medically important species of Staphylococci are:
Staphylococcus aureus (most important)
Stphylococcus epidermidis
Stphylococcus saprophyticus
Based on the production of Coagulase enzyme, Staphylococci can be classified into:
1- Coagulase positive-Staphylococci (Produce Coagulase enzyme)
Example: Staphylococcus aureus
2- Coagulase negative Staphylococci (Do not produce Coagulase enzyme) Examples: Staphylococcus epidermidis and Staphylococcus saprophyticus).
Note:
Coagulase is an enzyme induces coagulation of plasma by activating prothrombin to form thrombin. Thrombin in turns catalyzes the activation of fibrinogen to form fibrin, which causes clot formation

5. Staphylococcus aureus:
Epidemiology and Transmission:
Approximately 30-50% of people harbor Staphylococcus aureus in their anterior nares. It is also found in the vagina of approximately 5% of women
From the anterior nares, Staphylococcus aureus may spread to the skin and throat
Staphylococcus aureus may be found almost every where around us ( tables, bed, clothes…..)
Hand contact is an important mode of transmission
Most Important virulence factors that can be found in Staph aureus:
1- Teichoic acid: involved in attachment and may cause septic shock
2- Collagen-binding proteins: involved in attachment to collagen and explain why this bacterium is common in causing wound infection
3- Exotoxins:
Connective tissue degrading enzymes such (proteases such as collagenase and elastase), lipases, hyaluronidase.
Pore-forming toxins such as PV Leukocidin (inactivate and kill leukocytes)
Toxic Shock Syndrome Toxin (TSST): a super-antigen that mediate non-specific activation of T cells and consequently leads for the production of massive amounts of cytokines.
Exfoliative toxin: involved in scalded skin syndrome
Enterotoxin B: it is heat stable and it is involved in food poisoning

6. Staph aureus infections:
A- Local skin infections:
A local inflammation that is characterized by tissue destruction and and pus formation and accumulation such as folliculitis, boils and wound infection.
When these infections become massive, they lead for the formation abscess (furuncles, carbuncles) formation that can be associated with high fever (pyogenic inflammation))
B-Systemic infections:
From major abscesses, S aureus reaches the blood stream (septicemia that can be associated with septic shock ) and thus can get seeded in different tissues and organs to cause internal infections (abscesses) in these locations. Examples: endocarditis, osteomyelitis, meningitis, pneumonia.
Note: septic shock can be induced by Teichoic acid and/or TSST

7. Symptoms of septic shock:
Initially: High fever and Tachycardia
Later on: decrease in body temperature, disseminated intravascular thrombosis , bleedings, sudden drop in blood and circulatory collapse, Multiple organ failure, comma, cardiac arrest and death

8. Other diseases caused by S aureus:
Non-pyogenic skin infection such cellulites and impetigo
Scalded-skin syndrome: (occurs most frequently in children)
Some strains of S aureus produce epidermolytic toxins known as Exfoliative toxins, which are proteases that specifically cleave desmogleins of superficial layers of the skin.
This results in a clinical condition known as Scalded Skin Syndrome (Ritter’s Syndrome) that is characterized by fever, large areas of skin slough, secondary skin infections and electrolyte imbalance can occur.

9. Food poisoning:
Some strains of Staph aureus produce a heat-stable and an acid-stable exotoxin known as Enterotoxin B.
Ingestion of food heavily contaminated with such kinds of S aureus strains result in a self-limiting vomiting that could be associated with watery diarrhea
Enterotoxin B is a super-antigen induces production of cytokines from mesenteric lymph nodes after ingestion of food contaminated food. These cytokines stimulate the intestinal nervous system, which in turns, stimulate the vomiting center in the brain.

10. Staphylococcus epidermidis and Staphylococcus saprophyticus
Both are two coagulase-negative Staphylococci.
Staphylococcus epidermidis:
It is part of the normal human flora on the skin and mucous membranes.
It commonly infects intravenous catheters and prosthetic implants, e.g., prosthetic heart valves (endocarditis), vascular grafts, and prosthetic joints (arthritis or osteomyelitis)
It is also a major cause of sepsis in neonates and of peritonitis in patients with renal failure who are undergoing peritoneal dialysis through an indwelling catheter.
Staphylococcus saprophyticus:
It causes urinary tract infections, particularly in sexually-active young women.

11. Classification of Streptococci:
Streptococci are spherical Gram-positive cocci that arranged in chains. The shortest chain of Streptococci consists of a pair of cocci (diplococci).
All streptococci are:
Catalase-negative (Remember, Staphylococci are Catalase-positive)
Non-motile
Facultative anaerobes
Classification of Streptococci:
I- According to their hemolytic activities:
Based on the hemolytic activities of the colonies of different Streptococcal species seen on Blood agar, Streptococci are classified as:
1-Alpha Hemolytic Streptococci: form a green zone around their colonies as a result hemoglobin oxidation.
2- Beta-Hemolytic Streptococci: form a clear zone around their colonies due to complete lysis of the red cells occurs. (These species of Streptococci produce pore-forming exotoxins known as hemolysins. Hemolysins form pores in the membrane of red blood cells and cause their hemolysis (hence the name hemolysin). However, it has been found that these toxins can form pores in the membrane of other type of cells as well.
3-Gamma Hemolytic Streptococci: These are non-hemolytic species of Streptococci (no change is seen o blood agar around their colonies)

12. Streptococcus agalactiae occurs in the vagina and colon
II- According to Lance-field Grouping:
Lance-field Grouping is based on a particular CHO antigen of the wall of MOST Beta hemolytic Streptococci, known as C carbohydrate.
According to this classification, there are currently 18 groups, ( A, B, C D…….)
Most Streptococcal infections are caused by members of Streptococci that are part of the human microbiota. Accordingly, most Streptococcal infections are endogenous infections.
Examples:
Viridans streptococci and Streptococcus pneumoniae are found mainly in the oropharynx
Streptococcus agalactiae occurs in the vagina and colon
Enterococci and anaerobic Streptococci are located in the colon

13. Streptococcus pyogenes (Beta-hemolytic/Group A)
It is the most important streptococcal pathogen. Some times, it be found transiently on skin and throat (it can be considered as a primary pathogen)

15. Diseases: Epidemiology and Transmission of Streptococcus pyogenes:
Epidemiology: Streptococcus pyogenes is the most common cause of throat infection (Pharyngitis) , specially among children.
Transmission: Respiratory aerosols
Diseases:
1- Pharyngitis:
Throat infection with Strep pyogenes can lead pyogenic inflammation (Pharyngitis/Sore throat/Strep throat).
Sore throat is characterized by a painful, swollen and inflamed tonsils with the formation of exudates, high fever, leukocytosis, and tender cervical lymph nodes.
Pharyngitis caused by some strains of Strep pyogenes that produces an exotoxin known as an Erythrogenic toxin, can be associated with a distinctive pink-red sandy skin rash and strawberry-colored tongue , a clinical condition that is known as Scarlet Fever.
Note: Step pyogenes produces an enzyme known as Streptokinase (fibrinolysin) that dissolve fibrin. Accordingly, it was possible to use this enzyme to dissolve fibrin in clots, thrombi, and emboli, Streptokinase is used to lyse thrombi in the coronary arteries of heart attack patients.

16. 2-Otitis media
3- Bronchitis and pneumonia
4- Bacteremia and Toxic Shock: bacteremia caused by Strep pyogenes can be associated with septic shock. Massive production of cytokines from T cells can be induced by its Erythrogenic Exotoxin A as well as its teichoic acid.
5- Meningitis
Skin infections caused by Step pyogenes: Step pyogenes can cause non-pyogenic skin infections such as cellulites and impetigo

17. Strep Gangrene (necrotizing fasciitis): skin infection caused by certain strains of Streptococcus pyogenes that produces a particular exotoxin known as Exotoxin B (a Cyteine protease) can cause severe necrotizing fasciitis that is characterized by massive tissue necrosis.
As the tissue dies, Streptococcus pyogenes enter the blood and rapidly spreads throughout the body causing sepsis and septic shock. This may lead to death.

18. Post-Streptococcal Diseases:
Some strains of Streptococcus pyogenes have certain M proteins with antigenic properties that is similar to certain antigens in human body that induce the formation of cross-reacting auto-antibodies.
As these cross-reacting antibodies bind to human antigens, to cause serious clinical conditions such as:
1- Acute Glomerulonephritis: which may lead to compete renal failure
2- Acute rheumatic fever: characterized by myocardial and endocardial tissue damage, especially in heart valves.

19. Streptococcus pneumoniae (Apha-hemolytic)
Streptococcus pneumoniae is an alpha hemolytic, Capsulated Gram-positive diplococci.
It is a member of the throat microbiota that colonize up to 50% of people. It is transmitted among people by respiratory aerosols.
Virulence and Pathogenesis:
Important virulence factor of Streptococcus pneumoniae include:
IgA protease:
Secretary IgA antibodies is secreted is the salvia and through the respiratory mucosa.
Streptococcus pneumoniae produces IgA protease , which degrades these antibodies to facilitate its attachment and colonization in throat.
Capsule: anti-phagocytic