Staphylococci 18 Student

Clinical Microbiology and Immunology
Staphylococcus
Cheryl Walter
11th October 2018
Staphylococcus 58258
Learning objectives
• Understand the diagnostic tools for differentiating
Staphylococcus from Streptococcus
• Understand what virulence factors are and how they
contribute towards pathogenesis in Staphyloccocal infections
• Understand the categories of virulence factors produced by S.
aureus and be able to describe key examples such as PVL,
ETA/ETB and TTST
• Understand the epidemiology pathogenesis mechanisms and
outcomes of Staphylococcal scalded skin syndrome (SSSS)
• Be able to list examples on how virulence factors are acquired
• Staphylococci and Streptococci two of the most medically

relevant groups of bacteria in existence
• Two genera of bacteria make up the majority of skin infections
in humans
• Important because so common, also because they can be
resistant to a number of antibiotics e.g. MRSA
• Have many similarities
- both Gram positive, facultatively anaerobic cocci
- both part of normal human microbiota
- some species are highly pathogenic, causing disease
indirectly e.g. toxins
• Also have key differences, making them easy to differentiate

- catalase + (staph) vs. – (strep)
-formation and cell division: clusters (staph) vs. chains (strep)
• Staph have typically characteristic antibiotic profile (resistant
to penicillin, gentamycin trimethoprim and tobramycin
• Staph very common isolate in orthopaedic samples
Staphylococcus
• Genus of at least 40 species
• Originate from Staphylococcaceae family
• Mostly reside on skin and mucosa of humans and other
animals
• S. aureus most well known and clinically relevant
• Other species not often identified; some catalase negative
S. aureus
• Common species, lives in soil, foods and on the

body
• Found in the nasal passages of 40-50 % of the
population and healthy reproductive tracts of
women
• Can cause minor skin infections as well as life
threatening sepsis
• MRSA is a serious sub-species of S. aureus that
is resistant to most β-lactam antibiotics
• Methicillin-resistant Staphylococcus aureus
S. aureus
Growth conditions
• Can be propagated on most medias

• Grows both anaerobically as well as
aerobically
• Colony appearance
-typically golden although can vary
from cream to orange
- coagulase negative species tend to
be white in appearance
S. aureus
Virulence factors
• Virulence factors are molecules produced by bacteria, viruses,

fungi, and protozoa that add to their effectiveness and enable
them to achieve the following: colonization of a niche in the
host (this includes attachment to cells)
S. aureus
Cell wall structure
S. aureus
Virulence factors
• Most often proteins that are secreted and/or associated with

the cell wall
• Cell surface factors ‘Adhesins’
a) MSCRAMMs (microbial surface components recognising
adhesive matrix molecules) such as:
• Protein A (binds proteins e.g. IgG)
• Fibronectin binding proteins
• Collagen binding proteins
• Clumping factor (binds fibrinogen)
b) Capsular polysaccharides
S. aureus
Virulence factors
• Most often proteins that are secreted and/or associated with
the cell wall
• Secreted factors (toxins, invasins and enzymes)
– Superantigens
• Staphylococcal enterotoxins (SEs) (serotypes A,B,C,D,E,G.
Also SE like (serotypes H,I and J-X)
• TSST-1
– Cytolytic toxins
• α/β/γ
– Leukocidins
• E.g. Panton-Valentine Leukocidin (PVL)
S. aureus
Virulence factors
• Exoenzymes i.e. secreted

– Lipases
– Nucleases
– Proteases (Both cysteine and serine proteases – targets those specific a.a. in order to break down peptide)
– Hyaluronidase
– Staphylokinase (digests fibrin, disintegrating mesh network that helps to localise infection )
– Coagulase (converts fibrinogen to fibrin – induces clots)

S. aureus
Pathogenesis and Virulence factors
• Panton-Valentine Leukocidin (PVL)

- Composed of two protein subunits that induce pore formation in
target cells
- Often produced by strains that cause skin infections as well as
haemorrhagic pneumonia
- Might work in concert with another virulence factor(s)
- Targets white blood cells, macrophages and monocytes
• Small Colony Variants (SCV)
- Slow growing morphological variants, in this case of S. aureus
- Implicated in persistent and relapsing infection
- auxotrophic
S. aureus
Pathogenesis and Virulence factors
• Resistance and Pathogenicity islands

- Genomic islands (evidence of horizontal gene transfer)
- e.g. SCCmec (staphylococcal cassette chromosome mec
(methicillin resistance) e.g. mecA
S. aureus
Cell wall structure
MRSA
• About 5 % of population are carriers – can be treated to

reduce carrier rates
• Carriers can spread MRSA to sick individuals (especially
hospital settings)
• Carriers asymptomatic
• Clean hands and screening campaign in NHS was highly
successful in reducing MRSA HAI
MRSA
MRSA – on the rise again?

MRSA infections
• S. aureus a ubiquitous skin species that often causes disease

• Systemic infections e.g. sepsis/bacteraemia, endocarditis,
meningitis
• Bone/joint infections e.g. osteomyelitis, septic arthritis
• Pneumonia
• Skin and soft tissue infections e.g. impetigo, folliculitis, wound
infection, boils, mastitis, cellulitis and necrotising fasciitis
MRSA
• Resistant to methicillin
• Acquired by mobile genetic element
• Resistance gene encoded for by mecA
• MecA is translated into the protein PBP2A – penicillin binding
protein 2A
– Binds β-lactam rings (albeit with a slow affinity)
– Blocks binding of antibiotics to bacterial cell walls
Screening of MRSA
• Samples taken on sabs from different body sites
• Selective (cefoxitin), chromogenic agars commonly used
• Molecular methods (Cepheid Xpert MRSA) $$$
• Screening of all patients before hospital admission (HRI - 700
patients a week)
• Carriers can be treated with antimicrobials baths or Mupirocin
spray for nasal carriers
Treatment of MRSA
• Clindamycin
• Tetracycline, doxycycline
• (Vancomycin)
Toxic Shock syndrome
• As name suggests, body’s reaction to toxin sends it into shock

• Serious, life threatening illness (Strep and Staph – associated)
• Identified in 1978, reported in 80s in previously healthy women
• Starts with flu-like symptoms, upset stomach; progresses to
very high fever, rash, hypotension, multiorgan failure and
peeling of skin on hands and feet
• Mostly associated with tampon usage in menstruating women
but 50 % of cases occur for other reasons
– Post-respiratory viral pneumonia/any soft tissue infection
– Anaphylactic TSS/extreme pyrexia syndrome
– Purpura fulminans
Toxic Shock syndrome

TSST-1
• Less than 10 % of all S. aureus isolates
carry genes encoding TSST-1 (tstH)
• TTST-1 is a superantigen – it causes a
massive T cell activation and release
of proinflammatory cytokines (20% of
pool!)
• These include: TNF-α and β, IL2, 6
and 12 as well as IFN-γ
• tstH gene originated from a mobile
genetic element (S. aurueus mobile
island 1)
Treatment of TSS
• Supportive measures
• Targeted antibiotic therapy (clindamycin*, flucloxacillin^,
rifampicin (vancomycin)
• Immunomodulatory therapy
• Requires ICU
• Mortality 5-20%
Skin infections
Skin infections
Staphylococcal Scalded skin syndrome (SSSS)
• Wide spread bullous type of impetigo

• Painful blisters are sites of infection that can spread
systemically and thus cover large swathes of skin
• Common in children, especially neonates but can affect those
with kidney disease or immunocompromised
• Blistering is induced by an exfoliative toxin (ET), which are
highly specific proteases, not superantigens
• Also known as Ritter von Ritterschein disease (in newborns)
SSSS
Localised infection
• Bullous impetigo, mildest version

of SSSS
• Characteristic, soft blisters form
that easily burst
• Surrounding skin healthy
• Not systemic
SSSS
Generalised infection
• Typically found in neonates 3-16 days old

• Initiated from a primary infection of umbilicus, inner ear,
conjunctiva or upper respiratory tract
• Mortality rate is lower than in adults unless complicated by co-
morbidities
SSSS
Presentation
• Malaise, irritability, poor feeding

• Initial infection (usually around head/neck) progresses to
patchy, painful rash
• Fever, do not want to be touched or held
• Development of large, fragile blisters
• Blisters rupture leading to sloughing off of sheets of epidermis
• Large areas of skin left exposed and raw
SSSS
Presentation
SSSS
Exotoxins
• At least two exfoliative toxins ETA and ETB

• Produced in roughly 5 % of S. aureus strains
• ETA encoded on the chromosome, ETB on a plasmid
• Both toxins are proteases that attack desmoglein-1 (DMG-1)
• DMG-1, a keratotinocyte involved in cell-to-cell attachment,
only found in superficial epidermis
• Levels of DMG-1 thought to decrease with age, explaining
frequency of SSSS in children
SSSS ETA and ETB

Site of action
• Toxins produced during the post exponential phase of

bacterial growth
• Excreted and absorbed into the systemic system
• Diffuse through dermal capillaries to reach the stratum
granulosum of the epidermis
• Proteolytic action and subsequent cleavage of DMG-1
• The presence of an unaffected different isoform, DMG-3, in
lower layers of skin protect these layers from exfoliation
SSSS ETA and ETB

Site of action
SSSS
Complications
• Co-infections: pneumonia, sepsis, osteomyelitis, septic

arthritis
• Immunosuppression
• Fluid loss from exposed skin
• Septic arthritis
• All important contributors to cases of mortality
SSSS
Treatment
• Infections respond well to antibiotics

• Most SSS-causing strains produce penicillinases
• Flucloxacillin, Vancomycin, oxacillin, Nafcillin, (clindamycin)
• Supportive treatment of wounds and exposed skin

Questions?
Learning resources
• Ford’s Medical microbiology pages 139, 272-
278
Learning objectives
• Understand the diagnostic tools for differentiating
Staphylococcus from Streptococcus
• Understand what virulence factors are and how they
contribute towards pathogenesis in Staphyloccocal infections
• Understand the categories of virulence factors produced by S.
aureus and be able to describe key examples such as PVL,
ETA/ETB and TTST
• Understand the epidemiology pathogenesis mechanisms and
outcomes of Staphylococcal scalded skin syndrome (SSSS)
• Be able to list examples on how virulence factors are acquired

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Clinical Microbiology and Immunology

• Staphylococci and Streptococci two of the most medically

• Also have key differences, making them easy to differentiate

• Common species, lives in soil, foods and on the

• Can be propagated on most medias

• Virulence factors are molecules produced by bacteria, viruses,

• Most often proteins that are secreted and/or associated with

• Exoenzymes i.e. secreted

– Coagulase (converts fibrinogen to fibrin – induces clots)

• Panton-Valentine Leukocidin (PVL)

• Resistance and Pathogenicity islands

• About 5 % of population are carriers – can be treated to

MRSA – on the rise again?

• S. aureus a ubiquitous skin species that often causes disease

Toxic Shock syndrome

• As name suggests, body’s reaction to toxin sends it into shock

Toxic Shock syndrome

• Wide spread bullous type of impetigo

• Bullous impetigo, mildest version

• Typically found in neonates 3-16 days old

• Malaise, irritability, poor feeding

• At least two exfoliative toxins ETA and ETB

SSSS ETA and ETB

• Toxins produced during the post exponential phase of

SSSS ETA and ETB

• Co-infections: pneumonia, sepsis, osteomyelitis, septic

• Infections respond well to antibiotics

• Supportive treatment of wounds and exposed skin

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