There are two medically important genera of
gram positive cocci: Staphylococcus and
Streptococcus. Staphylococcal infections range
from the trivial to the rapidly fatal. They can
very difficult to treat, especially those
contracted in hospitals, because of the
remarkable ability of Staphylococci to become
resistant to antibiotics. Staphylococci are
ubiquitous in nature, with about a dozen
species occurring as a part of human flora.
The most virulent of the genus, S.aureus , is
one of the most common causes of bacterial
infections
Staphylococci & Streptococci are non motile 
& do not form spores.
Both Staphylococci & Streptococci are gram 
positive cocci, but they are distinguished by
two main criteria.
*Microscoplly, Staphylococci appear in 
grape-like clusters, whereas Streptococci are
in chains.
*Biochemically, Streptococci produce 
catalase (ie, they degrade hydrogen
peroxide), whereas Streptococci do not.
General features of Staphylococci
Staphylococci generally stain darkely gram 
positive, they are round &tend to occur in
bunches like grapes. They are true
facultatively anaerobic org. They produce
catalase.
The most virulent spp. of Staphylococcus is

S.aureus, almost all isolates of which secrete
coagulase-an enzyme that causes citrated
plasma to clot. There are other spp. that
occasionally cause disease; these lack
coagulase & are often referred to as coagulase
negative Staphylococci
Staphylococcus aureus
S.aureus disease may be:

*Largely or wholly the result of actual invasive 
infection (that is, colonization), overcoming
host defense mechanisms, & the production of
extracellular substances which facilitate
invasion.
*A result of toxins in the absence of invasive 
infection. or
*A combination of invasive infection and 
intoxication.
Epidemiology
S.aureus is frequently carried by healthy

individuals on the skin & mucous
membranes. Carriers serve as a source of
infection themselves & others; ex, by
direct contact, by contamination of
fomites or food, which can then result in
food poisoning.
Pathogensis
S.aureus causes disease by infecting tissues typically

creating abscesses and/or by producing toxins. A
common entry point into the body is a break in the 
skin. Another portal of entry is the respiratory tract.
The localized host response to Staphylococcal
infection is inflammation, characterized by swelling, 
accumulation of pus, and necrosis of tissue.
Fibroblasts and their products may form a wall around 
the inflamed area, which contains bacteria &
leukocytes. This creates a characteristic, pus-filled
boil
or abscess. Serious consequences of staphylococcal 
infections occur when the bacteria invade the
bloodstream. The resulting septicemia may be rapidly 
fatal. Bacteremia may result in seeding internal
abscesses, skin lesions, or infections in the lung , 
kidney, heart, skeletal muscle, or meninges.
Pathogenic virulence factors are the genetic, 
biochemical, or structural features that enable
an organism to produce disease. The clinical
outcome of an infection depends on the
virulence of the pathogen and the opposing
effectiveness of the host defense mechanisms.
S.aureus produce many enzymes include
coagulase, fibrinolysin, hyaluronidase,
proteases, nucleases, & lipases.
Also these orgs expresses many potential 
virulence factors as follows:
Cell wall virulence factors 
a) Protein A is a major component of the 
S.aureus cell wall. It binds to the Fc
moiety of IgG, exerting an 
antiopsonin( and therefore strongly
antiphagocytic) effect. 
b) Fibronectin-binding protein (FnBP) 
and other staphylococcal surface
proteins promote binding to mucosal 
cells and tissue matrices.
2-Cytolytic exotoxins: α, β, γ, and δ toxins 
attack mammalian cell (including red blood
cell) membranes, and are often referred to
as hemolysins.
3-Superantigen exotoxins: These toxins have
affinity for the T cell receptor-MHC Class II
antigen complex. They stimulate enhanced T
lymphocyte response. This major T cell
activation can cause toxic shock syndrome,
primarily by release into the circulation of
inordinately large amounts of T cell
cytokines, such as interleukin-2
(IL-2), interferon- γ (IFN- γ), and tumor
necrosis factor- α (TNF- α).

Enterotoxins: Enterotoxins (six major 
antigenic types: A, B, C, D, E, and G)
are produced by approximately half of 
all S.aureus isolates. When these
bacteria contaminate food and are 
allowed to grow, they secrete
enterotoxin,
ingestion of which can cause food 
poisoning. Enterotoxins are
superantigens that are even more 
heat stable than S.aureus; therefore,
organisms are not always recovered 
from incriminated food
Toxic shock syndrome toxin (TSST-1) is
the classic cause of toxic shock
syndrome. Because of similarities in
molecular structure, it is sometimes
referred to as staphylococcal 
enterotoxin F (SEF), although it does not
cause
food poisoning when ingested. 
Exfoliatin (exfoliative toxin, ET) is also a
superantigen. It causes scalded
skin syndrome in children 



Clinical findings
The important clinical manifestations caused 
by S.aureus can be divided into two groups:
inflammatory & toxin-mediated.
1-Inflammatory 
Skin infections, such as impetigo, furuncles, 
carbuncles, folliculitis…..etc.
Septicemia can originate from any localized 
lesion, especially wound infection, or as a
result of intravenous drug abuse.
Endocarditis on normal or prosthetic heart 
valves.
Osteomyelitis and arthritis 
Pneumonia in postoperative patients or 
following viral respiratory infection.
Abscesses can occur in any organ when the 
organism circulates in the bloodstream
(bacteremia).
Toxin-mediated
Food poisoning caused by ingestion of 
enterotoxin, which is performed in foods &
hence has a short incubation period (1-8
hours).
Toxic shock syndrome is characterized by
high fever, hypotension, rash, vomiting,
diarrhea & multiorgan involvement
(especially GI, renal, &/or hepatic
damage). TSST causes toxic shock ,
especially in tampon-using menstruating
women or in individualswith wound
infections. Toxic shock also occur in
patients with nasal packing used to stop
bleeding from the nose. TSST is produced
locally by S.aureus in either the vagina,
nose, or other infected site. The toxin
enters the bloodstream, causing a
toxemia.

Scalded skin syndrome is 
characterized by fever, large bullae
resulting from the action of an
exfoliative toxin that attacks the
intracellular adhesive of the stratum
granulosum causing marked
epithelial desequamation.This
syndrome occurs most often in
young children
Lab. Diagnosis
Specimen: There are to be collected 
depending on the nature of lesion, pus
from suppurative lesions, CSF from
meningitis, blood from septicemia, sputum
from respiratory infection and suspected
food, vomit or faeces from food poisoning.
Smear: Examination of gram stained smear
of pus & other specimens shows gram
positive cocci in clusters with some single
& paired cocci.

Culture : Specimens inoculated on 
blood agar or mannitol agar (selective
media for Staph.aureus show typical
colonies on 18 hr incubation at 37
.ْْC
Coagulase test: the coagulase positive
strain is identified .
Typing test. 

Coagulase negative staphylococci
There are two coagulase negative 
staphylococci of medical importance:
S.epidermidis & S. saprophyticus.
S.epidermidis infections are almost always
hospital acquired, whereas S.
saprophyticus infections are almost always
community- acquired.
S.epidermidis is part of the normal human 
flora on the skin & mucous membranes but
can cause infections of intravenous
catheters & prosthetic implants, eg, heart
valves (endocarditis), vascular grafts, &
joints.
S.epidermidis is also a major cause of
sepsis in neonates & of peritonitis in
patients with renal failure who are

undergoing peritoneal dialysis through
an indwelling catheter.
It is the most common bacterium to
cause cerebrospinal fluid shunt
infections


S.epidermidis produces an

extracellular polysaccharide material
(sometimes called"slime") that
facilitates adherence to bioprosthetic
material surfaces, such as intravenous
catheters, & acts as a barrier to
antimicrobial agents.
S. saprophyticus causes urinary tract 
infections, particularly in sexually
active young women.
Streptococci
Streptococci are G+ve, non motile, & 
catalase-negative. Clinically important
genera include Streptococcus &
Enterococcus. They are ovoid to spherical
in shape, & occur as pairs or chains.
Because of their complex nutritional
requirements, blood-enriched medium is
generally used for their isolation.
Classification
1-Hemolytic classification 
α- hemolytic streptococci cause a chemical 
change in the hemoglobin of red cells in blood
agar, resulting in the appearance of green
pigment that forms a ring around the colony.
β - hemolytic streptococci cause gross lysis of
red blood cells, resulting in a clear ring
around the colony. Two types of β –
hemolysins are released. Streptolysin O
(inactivated by atmospheric oxygen) is
demonstrable only in deep colonies while
Streptolysin S ( oxygen stable) is responsible
for surface colony haemolysis.
γ- hemolytic is a term applied to 
streptococci that cause no color change
or lysis of red blood cells.
There are two important antigens of beta- 
hemolytic streptococci:
C- carbohydrate determines the group of β hemolytic streptococci. It is located in the
cell wall, & its specificity is determined by an
amino sugar

M protein is the most important virulence
factor & determines the type of group A β hemolytic streptococci.
It protrudes from the outer surface of the
cell & interferes with ingestion by
phagocytes (antiphagocytic).


There are approximately 80 Grifith serotypes 
based on the M protein, which explains why
multiple infections with S.pyogenes that
produce certain M protein types are
rheumatogenic ( cause primarily rheumatic
fever ), whereas strains of S.pyogenes that
produce other M protein types are
nephritogenic (cause primarily acute
glomerulonephritis). Although M protein is the
main antiphagocytic component of
S.pyogenes, the org also has a polysaccharide
capsule that play a role in retarding
phagocytosis.
There are approximately 80 Grifith serotypes
based on the M protein, which explains why
multiple infections with S.pyogenes that
produce certain M protein types are
rheumatogenic ( cause primarily rheumatic
fever ), whereas strains of S.pyogenes that
produce other M protein types are
nephritogenic (cause primarily acute
glomerulonephritis). Although M protein is
the main antiphagocytic component of
S.pyogenes, the org also has a
polysaccharide capsule that play a role in
retarding phagocytosis.

Serological classification (Lancefield) 
Many species of streptococci have a 
polysaccharide in their cell walls known as Ccarbohydrate.
The Lancefield scheme classifies primarily β hemolytic streptococci into groups A-U on the
basis of their C- carbohydrate.
The clinically most important groups of β hemolytic streptococci are types A & B.


Classification based on Schleifer & 
Kilpper-Balz
This classification depend on the basis of 
structure of the cell wall peptidoglycan
together with the G+C content of the DNA &
the results of DNA pairing.
They have divided the genus Streptococcus
into sex groups

Pyogenic streptococci – S.pyogenes
Pneumococci – S.pneumoniae 
Oral streptococci – S.mutans
Enterococci – S. faecalis 
Lactic streptococci – S.lactice
Other streptococci – S.bovis




Group A β-hemolytic streptococci 
S.pyogenes, the most clinically important 
member of this group of gram positive cocci,
is one of the most frequently encountered
bacterial pathogens of humans worldwide. It
can invade apparently intact skin or mucous
membranes, causing some of the most rapidly
progressive infections known. A low inoculum
suffices for infection. The growth of
S.pyogenes is inhibited by antibiotic
bacitracin, an important diagnostic criterion.
Structure 
1-Capsule (antiphagocytic) 
2-Cell wall 
a)Fimbriae: the fimbriae contain the 
major S.pyogenes virulence factor,
M protein. 
b)Group A-specific C-carbohydrate 
c)Protein F ( fibronectin- binding protein)
3-Extracellular products 

Epidemiology 
The only reservoir for S.pyogenes in 
nature is the skin & mucous
membranes of the human host.
Respiratory droplets or skin contact
spread Group A streptococcal infection
from person to person, especially in
crowded environments such as
classrooms or children's play area.

Pathology

S.pyogenes cells, perhaps in an inhaled

droplet, attach to the pharyngeal mucosa via
actions of protein F, lipoteichoic acid, & M
protein. The bacteria may simply colonize; the
patient is then considered colonized.
Alternatively, bacteria may grow & secrete
toxins, causing damage to surrounding cells,
invading the mucosa, and eliciting an
inflammatory response with attendant influx
of white cells, fluid leakage, & pus formation.
The patient then has streptococcal
pharyngitis.
Occasionally, there is sufficient spread 
that the blood stream is significantly
invaded, possibly resulting in septicemia
&/or seeding of distant sites, where
cellulitis (acute inflammation of
subcutaneous tissue), fasciitis
(inflammation of the tissue under the skin
that covers a surface of underlying
tissue), or myonecrosis (death of muscle
cells) may develop rapidly or insidiously.
Clinical findings 
1-Pyogenic diseases 
a-Sore throat ( acute tonsillitis/ & 
pharyngitis) is the commonest of
streptococcal diseases. The org may 
spread to surrounding tissue
causing complication like otitis media, 
mastoiditis,sinusitis,
meningitis, 
peritonitis & pneumonia 
b-Skin infection 
Local infections in superficial layers of skin
due to S.pyogenes
include impetigo & erysipelas. 

c-Other pyogenic diseases 
* puerperial sepsis ( postpartum infection
of uterus).
*Sepsis: Infection of wounds, burns, 
chronic skin lesion (eczema,
psoriasis). 
*Lymphadenitis, septicaemia, acute 
endocarditis, abscess in internal
organs (brain, liver, lung, & kidney). 

2- Toxigenic diseases 

a-Scarlet fever 
Scarlet fever occurs as a 
complication of streptococcal
infection
(sore throat) 
when the infecting strain produces 
erythrogenic toxin &
the patient has got no antitoxic 
immunity.

b- Streptococcal toxic shock syndrome 
This syndrome is mediated by 
pyrogenic exotoxins that function as
superantigens causing massive, 
nonspecific T- cell activation &
cytokines release. It is similar 
to staphylococcal toxic shock
syndrome. 
3-Immunogenic diseases ( non suppurative 
infection)
a- Acute glomerulonephritis(AGN): This rare, 
postinfectious sequela occur as soon as one
week after impetigo or pharyngitis ensues,
due to a few nephritogenic strains of group
A streptococci.
Antigen-antibody complexes on the 
basement membrane of the glomerulus
initiate the disease. The most clinical
features are hypertension, edema of the
face and ankles, & smoky urine (due to red
cells in the urine).
b-Acute rheumatic fever: this
autoimmune disease occurs two to
three weeks after the initiation of
pharyngitis.
 It is caused by cross reactions
between antigens of the heart & joint
tissues, & the streptococcal antigen
(especially the M protein epitopes). It
is characterized by fever, rash, carditis,
& arthritis.


Lab. Diagnosis 
1-Specimen: Throat swab, pus& lesion
samples, sputum, blood , spinal fluid
2-Smear: G+ve cocci in chains or pairs
are found association with pus cells.


3-culture: Specimen should be inoculated
immediately.

Specimen is inoculated in the blood agar 
for overnight. ْmedium & incubated at 37C
Hemolysis develops better under anaerobic
conditions or under 5-10% CO2.
The bacterial colonies are small, dry &
surrounded by β-hemolysis.

A simple technique of detection of 
S.pyogenes ( group A) is done by agar
plate test using paper discs impregnated
with bacitracin.
S.pyogenes is more sensitive to bacitracin 
than other streptococci. S.pyogenes can be
rapidly identified by fluoruesent antibody
technique.
4-Antigen detecting tests: ELISA, 
agglutination tests
5-Serological tests: test for 
streptococcal antibodies is not helpful in
diagnosing acute infection which may
be used to identify & confirm primary
infection.
They are more commonly used to 
diagnose non suppurative
complications.

Treatment 
S.pyogenes has not acquired

resistance to penicillin G, which remains
the antibiotic of choice for acute
streptococcal disease. In a pencillin
allergic patient , Macrolide such as
clarithromycin is the preferred drug.
Pencillin G plus clindamycin are used in
treating streptococcal toxic shock
syndrome.
Group B β-hemolytic streptococci 
Group B streptococci, represented by the pathogen 
S.agalactiae. It is an important pathogen in neonates
causing neonatal septicemia & meningitis. It is also
associated with septic abortion & puerperial sepsis.
S.agalactiae is a commensal of female genital tract
from where bacterial colonization in neonates occur.
Samples of blood, cervical swabs, spinal fluid can 
obtained for culture on blood agar. ELISA tests can
also demonstrate the presence of bacterial antigen in
these samples.
Most isolates remain sensitive to penicillin G & 
ampicillin, which are still the antibiotics of choice.
Enterococci 
Enterococci contain a C-carbohydrate 
that reacts with group D antisera. The
clinically most important species are E.
faecalis & E.faecium. Enterococci can
be α-,β-, or non hemolytic. As a rule,
enterococci are not very virulent, but
they have become prominent as a
cause of nosocomial infections as a
result of their multiple antibiotic
resistance.
Epidemiology 
Enterococci are apart of normal 
flora. However, they can also
colonize oral mucous membranes
& skin, especially in hospital
setting.
Diseases 
Enterococci seldom cause disease in 
normal, healthy individuals. But under
certain conditions, enterococci can
spread to normally sterile sites,
causing urinary tract infections (UTI),
bacteremia sepsis, subacute bacterial
endocarditis, biliary tract infection, or
intra-abdominal abscesses.
Non enterococcal group D 
streptococci
Streptococcal bovis is the most 
clinically important of the non
enterococcus group D streptococci.
S.bovis occasionally causes UTI &
subacute bacterial endocarditis.
Viridans streptococci 
The viridans group of streptococci includes 
many gram- positive, catalse-negative, α- or
γ-hemolytic species that constitute the main
facultative oral flora. The viridans
streptococci are relatively avirulent, but
streptococcus mutans & other members of
the viridans group cause dental caries. In
patients with abnormal or damaged heart
valves, they can also infect these valves
during a bacteremia, causing subacute
bacterial endocarditis.
Streptococcus pneumoniae 
(pneumococcus)
S. pneumoniae are gram positive, non 
motile, encapsulated cocci. They are lancetshaped, & their tendency to occur in pairs
accounts for their earlier designation as
diplococcus pneumoniae. Like other
streptococci, S. pneumoniae is fastidious &
routinely cultured on blood agar. It releases
an α-hemolysin that damages red cell
membranes, causing colonies to be αhemolytic.
Epidemiology

S. pneumoniae is an obligate parasite of

humans, & can be found in the
nasopharynx of many healthy individuals.
This org is extremely sensitive to
environmental agents pneumococcal
infections can be either endogenous or
exogenous.
Pathogensis
1-Capsule: S. pneumoniae polysaccharide 
capsule is both antiphagocytic & antigenic.
Antiphagocytic properties of the capsule
protect the bacteria from polymorphonuclear
leukocyte attack, facilitating growth of the
bacteria prior to the appearance of anticapsular antibodies. There are approximately
85 distinct capsular serotypes, some of which
endow strains with greater virulence than
others, as reflected by the fact that about
twenty serotypes account for vast majority of
pneumococcal infections.
2-Autolysin: This peptidoglycan 
hydrolyse is present in the bacterial cell
wall, & is normally inactive. However, it
is readily triggered (ex, by surface active
agents, β-lactam antibiotics, or aging),
resulting in cell lysis. Autolysin is thus
responsible for the release of
intracellular virulence factors.
3- Pneumolysin: Although retained within 
the cytosol of intact pneumococci,
pneumolysin is thought to be an important
virulence factor by virtue of its ability to
attack mammalian cell membranes,
causing lysis once it is release by autolysin
from the interior of the bacterium.
4-IgA protease: Pneumococci produce IgA 
protease that enhances the organism’s
ability to colonize the mucosa of upper
respiratory tract.
Clinical significance 
Acute bacterial pneumonia: A leading 
cause of death, especially in the aged
& those whose resistance is impaired,
this disease is caused most frequently
by S. pneumoniae .
Otitis media 
Bacteremia/ sepsis 
Meningitis 
Lab diagnosis 
Specimens can be obtained from a 
nosapharyngeal swab, blood, pus, sputum, or
spinal fluid. α-hemolytic colonies appear when
S. pneumoniae is grown on the blood agar.
Lancet-shaped, gram positive diplococci are
observed on gram stain of the sample. Growth
of these bacteria is inhibited by optochin , &
the cells are lysed by bile acids. Capsular
swelling is observed when the pneumococci
treated with type-specific antisera (Quellung
reaction).