Transcript Genus Staphylococcus

The Genus Staphylococcus
• Contains about 40 species and several
species have a number of “subspecies”
(Bergey’s Manual)
• The two we are concerned about are S.
aureus and S. epidermidis
• Gram-positive, non-motile cocci that
exist as “grape-like” clusters
• Each cell is almost perfectly spherical
and about 1 um in diameter
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Significance of Staphylococcus aureus in
Health Settings
From 1980-1989, in a large number of
participating hospitals, 26% of all nosocomial
infections were caused by coagulase-negative
S. aureus strains; 1992-1997, 40% of
bacteremias
Causes the most common type of food poisoning
reported
Side point: In US, 2,000,000 cases of nosocomial infections per
year. Added expenditure to patients estimated at $4.5 billion.
Highest rates of infection in: burn, neonatal, and pediatric ICUs.
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Staphylococcus aureus
Gram-positive, spherical cells
Cells organized in irregular clusters
resembling grapes
Facultative anaerobe (can ferment)
Yellow colonies on most media
www.hpa.org.uk/.../staphylo/images/Saureus.jpg
“Normal” member of nasal membrane,
nasopharynx, skin, perineum, GI tract
and genital tract
Causes a variety of infections including:
Furuncles (boils), carbuncles, impetigo, toxic epidermal necrolysis,
pneumonia, osteomyelitis, meningitis, endocarditis, mastitis,
bacteremia, abscesses, food poisoning, enterocolitis, urogenital
infections and toxic shock syndrome
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Suppurative infections
Toxic Shock Syndrome
Superficial skin lesions
Serious infections
Deep seated infections
Food poisoning
Nosocomial infections
www.textbookofbacteriology.net
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Many strains of S. aureus are hemolytic on blood agar plates.
Double zone of
hemolysis
Some strains produce two types of hemolysis:
Inner zone caused by a toxin
Outer zone caused by the b toxin
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Portals of Entry
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Spread via blood vessels
Skeletal muscle
Heart
Meninges
Kidney
Bone
Hair follicle
Scratch or cut
Needle stick
Surgery scars /sutures
Respiratory tract
Accumulation of pus
Tissue necrosis
GI tract
Inflammation
Fibrin clots
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Multifactorial Pathogen
• Many virulence factors
• Different virulence factors play
either leading or supporting roles
in the different diseases
– Virulence genes have been identified
– Individual roles of the gene products
have been investigated
– Mutants deficient in these traits are
less virulent in animal models
– Toxins purified
• Cause symptoms in animal models
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• Surface proteins
– Assist in the colonization of host tissues
• Adhesion for collagen
– Septic arthritis – infective arthritis
– Osteomyelitis – bone or bone marrow infection
• Clumping factor
– Fibrin/fibinogen binding protein
– Aids in attachment to blot clots & injured tissue
– Attachment proteins
• Epithelial tissue
• Endothelial tissue
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• Toxins that damage host membranes
– Hemolysins
• Almost all strains produce at least one or a
combination
• a
– Binds to a host cell receptor and causes osmotic lysis
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b
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Sphingomyelinase*
Degrades membranes with sphingomyelin
Most S. aureus strains don’t produce this
Gene for this protein is on bacteriophage
d
– Small peptide and its role is unknown
*Sphingomyelin is a lipid found only in some animal cell membranes9
particularly in nerve cells
Toxins that damage host membranes II
• Leukocidin – multicomponent protein
toxin that cause pore formation of
certain cells (e.g. leukocytes) – may not
cause lysis but damages cells
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• Exotoxins
– Exfoliatin toxin
• Epidermolytic toxin
• Scalded skin syndrome
• Causes separation between the layers of skin
– Enterotoxins
• Cause diarrhea & vomiting
• Responsible for staphylococcal food poisoning
• Six different types
– SE-A, B, C, D and G
– Leukotoxin (Leukocidin)
• Alter the permeability of the membrane of leukocytes
– Toxic shock syndrome toxin (TSST-1)
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Pseudoenterotoxin
Is not emetic
Systemic
Responsible for 75% of TSS
Superantigen
– Large amount of cytokines are released by over stimulated T cells
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• Avoid Phagocytes
– Coagulase
• Extracellular protein
• Binds & activates prothrombin
– Staphylothrombin
– Fibrinogen  fibrin
• Hypothesized that clots form and “hide” bacterial cells
– Clotting factor
• Fibrinogen binding protein on the bacterial cell surface
• Clots form
– Protein A
• Binds the FC region of IgG
• Disguises phagocytes
• Disrupts opsonization
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• Antiphagocytic Factors
– “Microcapsule”
• Thin and requires EM to visualize this capsule
• Capsule may only be produced in host
– Leukocidin
• Specifically attacks leukocytes
• Causes membrane damage but is not hemolytic
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• Invasions
– Assist in the spread of the bacterium
• Kinases
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Staphylokinase
Plasmogin activator protein
Lyses fibrin
Hypothesized to aid in bacterial spread
• Hyaluronidase
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• Survival Inside of Phagocytes
– Carotenoids
• Golden yellow pigment
• Detoxifies reactive oxygen compounds
– Strongly catalase positive
• Destroys H2O2 produced by phagocytes
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• Antibiotic resistance
– Strains of S. aureus isolated from hospitals are
resistant to antibiotics
• Association with nosocomial infections
– There are strains that are resistant to all commonly
used antibiotics
– Vancomycin used to be the remaining useful antibiotic
• Vancomycin resistance has been documented
• VRSA
– Methicillin resistant S. aureus
• MRSA
– Methicillin was developed in the late 1950s as a replacement for
penicillin
– MRSA strains were identified in 1961
– No longer used clinically
• Have multiple resistance
• There are countless MRSA strains
• Different degrees of resistance to various antibiotics
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• MRSA infections have increased
dramatically
– In 1974, infections by MRSA represented
2% of the total number of staph infections
– In 1995, this figure increased to 22%
– In 2004, infections by MRSA represented
63%
• MRSA is mainly transmitted to patients
via human hands of health care workers
– Healthcare-Associated MRSA
www.cdc.gov
• All health care workers must wash
their hands with with soap and water or
using an alcohol-based hand sanitizer
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VITAL SIGNS: REMEDIES; Tough Policies Against Infection
New York Times, July 27, 2004
Special supplies of clean coats and hand wipes, combined with tough policies on visitors and
jewelry, helped a British hospital unit cut hospital-acquired infections drastically, a new study
reports.
The effort, in the orthopedic unit of Broomfield Hospital in Chelmsford, was described by Dr.
Leela C. Biant in a recent article in BMJ, the journal of the British Medical Association.
Infections after knee and hip replacement surgery had more than tripled when patients were
placed among the general hospital population in 1998, after an orthopedic unit was shut, Dr.
Biant wrote. One patient died of an infection with drug resistant staphylococcus, called
MRSA.
In July 2000, the hospital's orthopedic surgeons set out to seal off a 28-bed ward from
infections. The first step was to limit the ward to orthopedic patients, who were tested
before surgery for signs of exposure to MRSA; patients who tested positive were restricted
to a second, smaller ward, where they were treated with antibiotics as a preventive measure.
Along with standard precautions against the spread of infection, nurses were given aprons
that they wore at the bedside and then discarded. All staff members washed their hands
before they approached a patient and afterward. Doctors wore coats from a supply that was
laundered daily. Watches were not allowed on the ward; the only jewelry permitted were
wedding rings and small earrings. Visitors were restricted to two at a time for two hours a
day only, and were forbidden to sit on the patient's bed. In the year before the policy began,
417 joint replacement operations had produced 43 infections, including nine MRSA cases, Dr.
Biant wrote. In the year after its introduction, 488 similar operations produced only 15
infections, none of which were drug resistant, she said.
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Community-Associated MRSA
• MRSA infections acquired by individuals
that have not been recently hospitalized
or had a medical procedure
– Within the past year
– Dialysis, surgery, catheters
• Community-Associated MRSA infections
present as skin infections including pimples
and boils
– Occur in otherwise healthy people.
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How does antibiotic resistance develop and spread?
• Random mutation in chromosomal genes
– Selection for resistant strains
• Lateral transfer of resistance genes
– R plasmids via conjugation
– R genes via transduction
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Summary of S. aureus virulence factors
www.textbookofbacteriology.net
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Carbuncle
www.humankinetics.com/.../246810_E3399.jpg
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Toxic shock syndrome
www.aafp.org/afp/20000815/804_f6.jpg
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• Toxic shock syndrome (TSS)
• Sudden onset of fever, chills, vomiting,
diarrhea, muscle aches and rash
• Rapidly progresses to severe and intractable
hypotension and multisystem dysfunction
• Desquamation, especially on the palms and
soles
– Shedding of the outer layers of the skin
– Can occur 1-2 wks after onset of the illness
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• TSS is associated with use of tampons
and intravaginal contraceptive devices
• Also occurs as a complication of skin
abscesses or surgery
• Risk groups include
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Menstruating women
Women using barrier contraceptive devices
Individuals that have undergone nasal surgery
Individuals with postoperative staphylococcal
wound infections
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S. aureus food poisoning
• Foods: meats, meat products, eggs, and
especially mayonnaise-based salads… and raw
milk (infection of the udder)
• Caused by enterotoxin that is heat-stable!
Cook food, kill bacteria and still get sick…
• Considered to be by many the most common
form of food poisoning (probably underreported)
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Pathogenicity of S. epidermidis
Little known about the pathogenicity of S.
epidermidis
- Implicated in plastic foreign body
implantations
- Cells can bind to fibronectin (deposited by
host onto implants)
- Cells can produce a slime resulting in
biofilm formation on implant – not a
glycocalyx but a secreted teichoic acid
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