1. Discuss the impact Staphylococcus Aureus has on human health
Staphylococcus Aureus (S.aureus) is a bacteria generally found in the nasal cavity, respiratory
tract and in the normal skin flora. It’s location is advantageous to exploit the host defences.
According to Salyers & Whitt, 2002, S.aureus colonises approximately 33% of the population with
25% being persistently colonised.
S.aureus also contaminates food, either sourced from animals or cross-over, causing food
poisoning. Routinely its classes as a hospital or community acquired infection, either from the
individual or another hosts resident species (Ford, 2014). But the species are become resistance
to antibiotics, causing an emergence of Methicllin Resistant Staphylococcus Aureus (MRSA). An
estimated 90% of reported cases are MRSA (Salyers & Whitt, 2002), both MRSA and S.aureus
having a significant effect on human health.
Bacterial Physiology -
S.aureus is a gram-positive cocci bacteria, 0.5um-
1um in diameter (Sleigh, Timbury, & Sleigh, 1998,
pp. 55–59). It forms ‘grape-like' clusters, as shown
in figure 1. They reproduce asexually through
binary fission in 2 planes, dividing a second time,
before the first division has finished, creating the
cluster morphology.
They are non-motile, lacking flagella and can’t
produce spores. They also are able to produce
toxins and invasions (surface proteins), such as
catalase which helps blood clot by binding
to prothrombin, meaning it reaction
positively to a catalase test.
They can grow in both aerobic and
anaerobic conditions, growing as golden
colonies, which according to Sleigh,
Timbury, & Sleigh, ranges from white to
orange. Additionally causing heamolysis
on blood agar plates and tolerating
selective agar, 5%-10% salt concentration.
Some strains are coagulase positive,
meaning this can’t be used as a diagnostic
tool. This may lead to incorrect diagnosis
which impacts treatments and control
measures along with impacting human
health.
Surface Adhesions are proteins which are
anchored to the cell wall via shortages,
see figure 2. Such as Protein A, a
superantigen which increases virulence and assists in evading the host defense systems. They
also produce toxins and surface proteins which increase virulence.
Pathogenicity & Virulence -
Figure 1 - An image of Staphylococcus Aureus
viewed at a 50000x magnification. (CDC,2011)
Figure 2 - Diagram of S.aureus, showing the detailed physiology of the
bacteria (J.T Foster, 2004)
2. Figure 3 - A table sowing various virulence factors and there
pathogenesis on the body. Adapted from Ford, 2014.
Figure 4 - A diagram of S.aureus pathogenesis on the
different parts of the body (Foster, 1996).
The virulence of S.aureus is mostly multifactorial, using a combination of enzymes, toxins,
antigens and superantigens produce by the bacteria, allowing them to infect the host (Naber,
2009).
S.aureus infection initially started after they inoculate the host usually due to their placement in the
host, such as exposure to the
mucosal linings. The host’s initial
exposure triggers up regulation of
virulence genes, which produce the
virulence factors, and range of
which can be seen in figure 3.
Once it has evades the host
defenses various virulence's factors
are able to cause a range of
disease. PVL (Panton-Valine
Leucidin) is a particularly
aggressive cytotoxin which is found
mostly in MRSA, but can be found
in other S.aureus strains (~5%), its
kills the leukocytes which fighting
the infection, and causes neurotic
skin & muscosa lesions and
pneumonia. (Lina et al, 1999). It
works by inducing pore in cell membranes, by secreting two toxins, LukS-PV and LukF-PV, they
act as subunits that assemble on the host cell membrane. They fit together creating a ring with a
centre port allowing the cell contents to leak out, causing cell lysis (Melles et al, 2011).
Toxic Shock Syndrome (TSS) is caused by
TSST-1 (Toxic Shock Syndrome Toxin 1), an
exotoxin. It cross-links with T cell receptors with
major histocompatibilty compelx class II (MHC-
II) on antigen presenting cells. This causes a
large scale T-cell and a large scale cytokine
release. They trigger an overwhelming
systemic inflammatory response that manifest
as septic shock and organ failure. TSST-1
causes 50% of non-menstrual cases and all
menstrual cases (Foster, 1996).
3. Figure 5 - A diagram of S.aureus infections associated
with inwelling devices around the body (Foster, 1996).
Figure 6- A diagram showing the S.aureus stages of
biofilm production, usually causes infections on
indwelling medical devices, see seen in figure 5 (Otto,
2008).
Protein A is a superantigen which is an abundant surface protein that is anchored to the bacteria
cell by shortages and avidly binding IgG by the complementary C1q region. It inhibits the humoral
immunity by acting as a b-lymphocyte, which interacts with the immunoglobulins and b-cell antigen
receptors; this cripples the immune system, meaning repeat infections can occur the host lackw a
strong antibody response (Ford, 2014). It binds the Fc portion of antibodies, rendering them
inaccessible to opsinins, impairing phagocytic attack. It also inflames lung tissue by binding to
tumor necrosis factor 1 (TNFR-1) receptors, playing a key role in the pathogenesis of staph
pneumonia. It can also promote biofilm production when the protein in covalently linked to the
bacteria cell wall and inhibits
phagocytic engulfment
(Parameswaran & Paital, 2010).
Other such factors include alpha-
hemolysin (alpha toxin) which causes
form formation lysising blood cell.
Phenol-soluble modulins (PSMs) also
cause cell lysis, mainly in erthcoytes as
well as skin & soft tissue infections.
They are all under agr locus control,
which control the expression of these
factors and their associated
pathogenicity, see figures 4 (Foster,
1996).
The host senses the pattern of
peptiglycan and lipoproteins on the cell surface, which initiates immune cell activation, to avoid
this, S.aureus has ways of avoiding the host defence system. It has the ability to avoid
opsonophagocytosis by expressing clumping factor A, protein A and inhibitors which prevent the
binding of opsonins meaning its less sucepatble to phagocytosis. It can also hide from the host
inside epithelial cells and macorphages. It can
resist neutrophil killing by secreting CHIP
(Chemotaxis Inhibitory Protein) and Eap
(Extracellular adherence protein), that block the
recognition of chemotactic factors and binding
to endothelial adhesion molecule. Inhibiting
ICAM-1 binding prevents leukocyte adhesion,
diapedesis and extravasation form the
bloodstream to infection site (Salyers & Whitt,
2002, pp. 197-228).
S.aureus has the ability to produce a biofilms
which allows the bacteria to cause infections on
indwelling medical devices, as seen in figure 5.
Proteins such as allow attachment to host
proteins like fibrinogen, which is followed by the
maturation were adhesive proteins like cationic
glucosamine-based exopolysaccaride that
aggregates the cells into forming the typical
biofilm structure, as seen in figure 6. The biofilm then detaches for dissemination, which can be
due to blood flow in a vessel or other detachment factors (Otto, 2008).
Iron is needed for bacteria oxidative phosphorylation in metabolism, enzyme function, however it
isn't readily available. In order to acquire iron, S.aureus secretes iron-binding compounds such as
aureochelin and staphyloferrin, which capture the haemogolbin and haptoglobin from the host cell
surface (Liu, 2009). One the bacterium has sequestered iron it's able to use it to produce the
virulence factors which cause the disease states on the human hosts.
4. o Figure 7 - A table showing the incidence of S. aureus bacteremia per 10
0,000 person-years in different subpopulations and geographical regions
(Tong,Davis, Eichenberger, & Holland, 2015).
o Figure 8 - A table showing the primary foci of infections in cohorts with S.aureus bacteria
o table (Tong, Davis, Eichenberger, & Holland, 2015).
Disease States -
S.aureus pathogenicity and
virulence allow it cause a
range of disease states,
usually it’s a normal
commensal bacteria found on
the skin and in the nasal
cavity. One of the hallmarks of
S.aureus is that its causes
repeat infections through a
person's life (Naber, 2009).
S.aureus is widely spread
through different sub-
populations and geographical
regions Figure 7 shows the
incident across these regions.
Figure 8 shows the foci of the
infections, showing the
incident numbers for different
infections, with these being as
equally spread.
It can cause a wide range of
infections such as superficial
skin lesions (boils) with
infections ranging from benign impetigo to more life threatening cases, with 57%-85% of impetigo
in children is cause by
S.aureus. It can also
cause more deep
seated infections such
as osteomyelitis and
endocarditis, or
surgical site infections
or in medical devices
shown in figure 5. It
can also cause other
conditions such as
Pneumonia, food
poisoning and toxic
shock syndrome
(Foster, 1996).
Surgical site infections occur in 2%-5% of surgeries, with 30% being due to S.aureus with 44% of
the infections being MRSA. The biofilms adhere to the prosthetic material, which acts a sanctuary
site protecting the organism from antibiotics and the immune system, which proves difficult for
treatment (Tong, Davis, Eichenberger, & Holland, 2015).
Toxic shock syndrome was spread through super absorbent tampons which acting as a breeding
ground and absorbed through the vagina and then into the blood stream, here they cause the
cytokine release which flood the system causing the body to go into shock (Foster, 1997).
Toxic shock syndrome can be fatal in a few hours, but with the right healthcare interventions
someone can recover in a few weeks.
5. o Figure 9 - A table showing the active agents and the
agents that lack useful activity, in S.aureus treatment
(Greenwood, Slack, & Peutherer, 2002).
o
Healthcare Interventions -
Healthcare interventions are used to help treat, if possible, the range of disease states S.aureus
causes. Before healthcare interventions such as antibiotics there was a fatality rate of ~80%
(Tong, Davis, Eichenberger, & Holland,
2015).
Indwelling medical devices, such as
prosthetic devices are untreatable with
antibiotics, the treatment is usually to
replace the device within 2 steps, with a
>90% cure rate. If a replacement is
unfeasible then a long term antibiotic
suppression is used. Antibiotics such as
vancomycin is given for a period of weeks,
before the device and infected tissue are
removed, and IV antibiotic is administered and
then a second operation takes place to
implant a new prosthetic. Vancomyosin has
a poor bone penetration and low clinical cure
rates so alternative agents may be used if the
infection has penetrated the bone, like
linezilid (Tong, Davis, Eichenberger, &
Holland, 2015).
However due to the increased use of antibiotics, there has been an increase in the number of
cases of antibiotic resistance case, particularly MRSA (Baddour, 2010). 90% of S.aureus strains
are also found to be resistant to benzylpenicillin, along with those mentioned in figure 9, which are
all resistant to all the β-lactam agents. The resistance gene, mecA codes for the penicillin binding
protein that can be chromosonally transmitted. Glycopeptides like vancomycin or teicopinin are
used to treat MRSA infections but they are highly toxic and expensive.
Flucloxacillin is often given for all S.aureus treatment, unless MRSA is prevalent in the area,
where vancomycin is used, it's also used if the patient has a penicillin allergy (Greenwood, Slack,
& Peutherer, 2002). - 1653
Conclusion -
In conclusion S.aureus is a pathogen which is uniquely evolved to infiltrate the human host,
especially with the increased mutations causing antibiotic resistance such as MRSA. These are
making it increasingly difficult to fight off the infection despite the healthcare interventions, and if
not carefully monitored could mean S.aureus becomes untreatable.
It contains a wide range of virulence factors which increase its pathogenicity that causes a wide
range of disease states, that range from mild benign impetigo infections which can be easily
treated with antibiotics, or a deep seeded surgical site infections that needs 2 operations and
serval long courses of antibiotic as treatment.
S.aureus had a huge impact on human health with the wide range of toxins and superantigens it's
capable of producing, which can cause a wide range of disease states, that all have a significant
impact on human health. Without healthcare interventions and the necessary treatment they would
all eventually become fatal.
Word Count - 1808
6. References -
Baddour, M. M. (2010). MRSA (methicillin resistant staphylococcus aureus) infections and
treatment. New York: Nova Science Publishers.
CDC. (2011, January 17). Staphylococcus aureus pneumoniae in healthcare settings - HAI..
Ford, M. J. (2014). Medical microbiology (2nd ed.). Oxford: Oxford University Press.
Foster, T. (1996). Staphylococcus - Medical Microbiology (4th Edition ed.). University of Texas:
NCBI Bookshelf.
Foster, T. J. (2004). The staphylococcus aureus “superbug.” Journal of Clincal Invesitagtion,
114(12), . doi:10.1172/JCI23825
Greenwood, D., Slack, R. C. B. B., & Peutherer, J. F. (2002). Medical microbiology: A guide to
microbial infections ; pathogenesis, immunity, laboratory diagnosis and control (16th ed.).
Edinburgh: Churchill Livingstone.
Lina, G., Piémont, Y., Godail-Gamot, F., Bes, M., Peter, M.-O., Gauduchon, V., … geralina
@émont (1999). Involvement of Panton-Valentine Leukocidin—Producing staphylococcus aureus
in primary skin infections and pneumonia. Clinical Infectious Diseases, 29(5), 1128–1132.
doi:10.1086/313461
Liu, G. Y. (2009). Molecular pathogenesis of staphylococcus aureus infection. Pediatr Res, 65(5 Pt
2), . doi:10.1203/PDR.0b013e31819dc44d
Melles, D., van Leeuwen, C., Boelens, W. B., Peeters, H., Verbrugh, J. K., van Belkum, H., & van
Belkum, A. (2011). Panton-Valentine Leukocidin Genes in Staphylococcus aureus. Emerging
Infectious Diseases, 12(7), 1174–1175. doi:10.3201/eid1207.050865
Naber, C. (2009). Staphylococcus aureus Bacteremia: Epidemiology, Pathophysiology, and
Management Strategies. Clinical Infectious Diseases, 48(Supplement 4), . doi:10.1086/598189
Otto, M. (2008). Staphylococcal Biofilms. Current Top Microbiology & Immunology, 322, 207–228.
Parameswaran, N., & Patial, S. (2010). Tumor necrosis Factor-α signaling in Macrophages.
Critical Review Eukaryotic Gene Expression, 20(2), 87–103.
Salyers, A. A., & Whitt, D. D. (Eds.). (2002). Bacterial pathogenesis: A molecular approach (2nd
ed.). Washington, DC: American Society for Microbiology.
Sleigh, D. J., Timbury, M. C., & Sleigh, J. D. (1998). Notes on medical bacteriology (5th ed.).
Edinburgh: Churchill Livingstone.
Tong, S. Y. C., Davis, J. S., Eichenberger, E., & Holland, T. L. (2015). Staphylococcus aureus
infections: Epidemiology, Pathophysiology, clinical manifestations, and management. Clinical
Microbiology Reviews, 28(3), 603–661. doi:10.1128/CMR.00134-14
7. Faculty of Health and Wellbeing - Department of Biosciences
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