Team:SDU-Denmark/Background

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=Staphylococcus aureus=
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==Clinical and epidemiological importance==
 
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Staphylococcus aureus is a gram-positive bacterium that colonizes the skin of about 30% of healthy
 
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humans. Although mainly a harmless coloniser, S. aureus can cause severe infection. Its oxacillinresistant
 
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form (methicillin-resistant S. aureus, MRSA) is the most important cause of antibioticresistant
 
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health care-associated infections worldwide (26). Since health care-associated MRSA
 
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infections add to the number of infections caused by methicillin-susceptible S. aureus, a high incidence
 
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of MRSA adds to the overall burden of infections caused by this species in hospitals (20). Moreover,
 
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infections with MRSA may result in prolonged hospital stay and in higher mortality rates (7), owing
 
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mainly to the increased toxicity and limited effectiveness of alternative treatment regimens. MRSA
 
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is currently the most commonly identified antibiotic-resistant pathogen in hospitals in many parts of
 
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the world, including Europe, the Americas, North Africa and the Middle- and Far-East.
 
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==Resistance mechanisms==
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S. aureus acquires resistance to methicillin and all other beta-lactam antibiotics through expression
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of the exogenous mecA gene, that codes for a variant penicillin binding protein PBP2’ (PBP2a) with
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low affinity to beta-lactams, (21), thus preventing the drug induced inhibition of cell wall synthesis.
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The level of methicillin resistance (defined by its minimum inhibitory concentration, MIC) depends
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-
on the amount of PBP2’ production, which is influenced by various genetic factors. Resistance levels
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of mecA-positive strains can thus range from phenotypically susceptible to highly resistant (5). Upon
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challenge with methicillin, a population of a heterogeneously resistant MRSA strain may quickly be
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outgrown by a subpopulation of highly resistant variants.
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Glycopeptide antibiotics include vancomycin and teicoplanin. Both are very large molecules that
 
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through binding to the terminal amino acid residues (D-alanyl-D-alanine) of the peptide side chains
 
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in the growing peptidoglycan polymers inhibit the cross linking essential for cell wall stability. It is
 
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estimated that to block cell wall synthesis effectively, the glycopeptide antibiotic has to penetrate
 
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about 20 peptidoglycan layers, all with free D-alanyl-D-alanine targets, without being ‘trapped’,
 
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and this together with a poor penetration into infected tissues, limits the therapeutic effects of glycopeptides.
 
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Cell wall thickening of S. aureus thus increases its ability to resist vancomycin, and in S.
 
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aureus most strains with reduced vancomycin susceptibility have a markedly thicker cell wall (21).
 
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Vancomycin resistance is far more prevalent among enterococci, owing to different genetic resistance
 
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determinants.
 
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==Staphylococcus aureus resistance trends: 1999-2007==
 
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===Beta-lactams===
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=Description of ''S. aureus''=
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In 2007, 31 countries reported AST results of 31,591 invasive S. aureus isolates to EARSS, of which
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[[Image:SDU-Denmark-Saureus.jpg|200px|thumb|right|Figure 1. ''S. aureus'', colored.]]
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22% (n=7,115) were identified as MRSA. At least thirty-eight percent (n=2,736) of these MRSA
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isolates were confirmed by oxacillin MIC, PCR mecA-gene, or PBP2A-agglutination.
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MRSA proportions vary from 0% in the north to over 50% in southern European countries. Thirteen
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-
countries reported MRSA proportions equal or higher than 25%. Like previous years, all Mediterranean
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countries, Romania, the United Kingdom and Ireland were included in this category. In the
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-
UK, yet another year of decreasing MRSA proportions turned the increasing trend that prevailed
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-
until 2006 into a decrease, although this finding was not found by the subset analysis of laboratories
+
-
that consistently provided data for the entire EARSS observation period (9 years). In France, Turkey
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-
and Slovenia, the MRSA proportions are still on the decrease and for the first time in 2007 proportions
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-
in Austria, Bulgaria and Italy also showed a significant decrease (not confirmed for the subset
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-
laboratories in Austria and Italy). Significant increases reported in 2006 continued in 2007 in Czech
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-
Republic, Hungary and Germany (Figure 4.8).
+
-
Four countries had MRSA proportions over 40%, of which Portugal and Malta still show a continuing
+
''Staphylococcus aureus'', also known as golden staph, is the most common cause of staphylococcus infections. It is a gram positive bacterium, that normally can be treated with penicillin. Unfortunately they are becoming more and more resistant to common antibiotics and thereby harder to treat ([http://www.denstoredanske.dk/Krop,_psyke_og_sundhed/Sundhedsvidenskab/Farmakologi/penicillin 1]).
-
increase. In Greece, like last year, the subset laboratories showed a significant decrease, which
+
-
was not confirmed by the overall trend. The same holds for an increase in Spain. These differences
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-
between the total and the subset laboratories are caused by changes in the national EARSS participation
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-
over the years.
+
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In the northern part of Europe, MRSA rates are below 3%, except for the Baltic States (8%-9%). In
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The nose is regarded as the major site of ''S. aureus'' infection and from there the organisms can spread to other parts of the body. About 20% of the human population are long-term carriers of ''S. aureus''. Frequently part of the skin flora is contaminated ([http://cmr.asm.org/cgi/reprint/10/3/505?view=long&pmid=9227864 2]).
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Latvia, MRSA rates continue to decrease strongly, from 25% in 2004 to 8% in 2007. However, in the
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Netherlands, Finland and Denmark a significant increase was reported, although in Denmark not in
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the subset laboratories. The MRSA rates of Estonia, Iceland, Norway and Sweden remain relatively
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-
stable. In Belgium, the decrease of 2006 was maintained, although not (yet) reflected as statistically
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-
significant trend (Figure 4.9).
+
-
===Glycopeptides/vancomycin===
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Transmission of ''S. aureus'' to surgical wound via the skin in patients who are nasal carriers could be an explanation for endogenous infection. Preoperative disinfection is not as effective in the deeper layers of the skin, and ''S. aureus'' may thus become a source of infection during surgery ([http://cmr.asm.org/cgi/reprint/10/3/505?view=long&pmid=9227864 2]).
-
Overall, four confirmed VISA’s and no VRSA were reported to the EARSS database in 2007.
+
The ability to control staphylococcal infections in the future will depend on many factors, e.g., development of new therapeutic agents, optimization of infection control measures, and introduction of new medical devices with a reduced risk of infection ([http://cmr.asm.org/cgi/reprint/10/3/505?view=long&pmid=9227864 2]).
-
Vancomycin intermediate resistant S. aureus were reported by France (n=1), Ireland (n=1) and The
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-
Netherlands (n=2).
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==MRSA by hospital department==
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==Pathogenesis==
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S. aureus susceptibility data reported to EARSS originate from different hospital departments. Across
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[[Image:SDU-Denmark-Staph_scalded_skin_syndrome.png|200px|thumb|right|Figure 2. Scalded skin syndrome. From Dennis Kunkel, Microscopy Inc.]]
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the national EARSS networks, an average of 12% (min. 2%, max.26%) of the invasive S. aureus isolates
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was isolated from ICU patients. MRSA strains are more frequently isolated from ICU patients
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than non-ICU patients, and therefore country-specific differences in enrolment can be of influence on
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the comparability of the overall MRSA proportions.
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In 22 of 30 countries the MRSA proportions in ICU were higher compared to non-IC units; for twelve
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‎[[Image:SDU-Denmark-Saureus-MRSA_abcess.png‎|200px|thumb|right|Figure 3. Abscess. [http://scmsociety.typepad.com/mrsa/mrsa-patient-information.html (6)]]] 
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countries this difference was significant. In six countries, the MRSA proportions in ICU-isolates
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were lower than in the non-ICU isolates. Two countries had no MRSA isolates at all (Figure 4.10).
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In six countries, Croatia, Greece, Israel, Malta, Portugal, Turkey, the proportion of MRSA found
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among ICU patients was over 60%. Although in these counties, except for Malta, the MRSA proportions
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in ICUs were significantly higher compared to non-IC units, these high levels go together
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with high rates of MRSA, above 30%. However, high specialisation of ICU’s with very vulnerable
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patients could have been of influence.
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==Conclusions==
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''S. aureus'' is considered a opportunistic pathogen as it can cause infections, while at the same time being part of the normal flora. ''S. aureus'' is currently the most common cause of infections in hospitalized patients, with postoperative wound infections being an especially big problem ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 3]).
-
MRSA is still an increasing problem all over Europe. In a number of low-endemic countries increasing
+
The success of ''S. aureus'' as a pathogen, and its ability to cause such a wide range of infections, are the result of its extensive virulence factors such as toxins ([http://www.journals.uchicago.edu/doi/abs/10.1086/520289 4], [http://www.medicinenet.com/staph_infection/article.htm 5]).
-
MRSA proportions are found. In the high endemic countries, on the other hand, some countries seem
+
 
 +
''S. aureus'' infections are plentiful and diverse. The most common infection is of the skin as impertigo, cellulitis or less frequent scalded skin syndrome ([http://www.medicinenet.com/staph_infection/article.htm 5]).
 +
 
 +
If the bacteria enters the bloodstream, a condition known as sepsis, the bacteria can spread to organs with many serious complications, death often being the result ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 3]).
 +
 
 +
<div style="clear:both;"></div>
 +
 
 +
==MRSA==
 +
 
 +
Methicillin-resistant Staphylococcus Aureus (''MRSA'') is defined as a strain of ''S. aureus'' that is resistent to beta-lactam antibiotics, which includes common drugs such as penicillins and the cephalosporins ([http://en.wikipedia.org/wiki/MRSA 7]).
 +
 
 +
''MRSA'' can cause the same serious infections as other strains of ''S. aureus'', but is especially troublesome, because of it's resistance to the most common antibiotics.
 +
 
 +
In the United States, invasive (i.e., serious) "MRSA" infections occur in approximately 94,000 persons each year and are associated with approximately 19,000 deaths ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 8]).
 +
 
 +
Several antibiotics with the ability to kill ''S. aureus'' have been made, such as vancomycin and teicoplanin, both drugs that are used to treat ''MRSA'' infections today. The absorption of these drugs is very low, for which reason it has to be administrated intravenously. This administration route is not optimal. Moreover new strains has been discovered that are resistant to vancomycin, called ''VRSA'' (vancomycin-resistant Staphylococcus aureus) ([http://en.wikipedia.org/wiki/MRSA 7]). 
 +
 
 +
To be able to treat patients with ''S. aureus'' infections in the future, new antibiotics and new methods of treatment most be found.
 +
 
 +
=Biofilm Formation=
 +
 
 +
 
 +
''S. aureus'' pathogenecity depends on quorum-sensing and biofilm formation. Biofilm is a layer of microbes embedded in an extracellular slime/adhesive, usually polysaccharide material excreted by the cells and attached to a surface ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 9]).
 +
 
 +
A biofilm facilitates a microenvironment suited for the bacteria. It improves adhesion to the host; it protects the bacteria from hostile environments; and it may confer relative resistance by shielding the bacteria from antibiotics.
 +
 
 +
''S. aureus'' biofilm formation depends on two quorum-sensing systems, leading to expression of ''RNAIII'' that regulates expression of genes involved in pathogenesis. Other staphylococcus strains have developed a ''RNAIII-inhibiting peptide (RIP)'' that quenches quorum-sensing, and reduces ''RNAIII'' transcription and biofilm formation in ''S. aureus'' ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 10]).
 +
 
 +
[[Image:SDU-Denmark-Slimy_business.jpg|340px|thumb|left|Figure 4. The five stages of bacterial biofilm formation. (A) Bacteria reversibly attach to solid support. (B) Bacteria become irreversibly attached, and aggregate to form matrix. (C) Maturation phase: cells become layered and effects of quorum sensing begin. (D) Clusters reach maximum thickness. (E) Escape of planktonic bacteria from matrix dispersion. From Slimy business — the biotechnology of biofilms; Nature 21, 361 - 365 (2003)]]
 +
 
 +
[[Image:SDU-Denmark-Staphylococcus_aureus_biofilm_01.jpg|200px|thumb|right|Figure 5. S.aureus biofilm [http://en.wikipedia.org/wiki/File:Staphylococcus_aureus_biofilm_01.jpg (11)] ]]
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<div style="clear:both;"></div>
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=Quorum-sensing=
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Quorum-sensing bacteria produce molecules, termed autoinducers, that function as chemical signal molecules. The concentration of these signals increase as a function of the number of cells in a colony. Using this chemical signaling, the bacteria can adapt to the current situation, and like a multicellular organism synchronize their behavior. The colony of bacteria forms biofilms, that are sessile microbial communities embedded in a self-produced extracellular polymeric matrix, with the advantages described above ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 12]).
 +
 
 +
The strategy is that bacteria at a low level will express protein factors that promote attachment and colonization, whereas they at lager scale will repress these genes and instead express genes of toxins and proteases,  factors that are required for dissemination ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 13]).
 +
 
 +
In ''S. aureus'' the genes involved in quorum-sensing are encoded by the ''agr''-locus ('''a'''ccessory '''g'''ene '''r'''egulator) system ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 12]).
 +
 
 +
Two different promoters ''P2'' and ''P3'' drive the two operons of the ''arg''-locus. The ''P2'' operon codes for a ''RNAII'' transcript, while the P3 promoter drives transcription of ''RNAIII''. RNAIII is an important part of the system as it regulates at least 15 genes coding for potential virulence factors ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 13]).
 +
 
 +
The synthesis of ''RNAIII'' is regulated by quorum-sensing molecules. When the autoinducers of the system reach a threshold concentration ''RNAIII'' is synthesized. The described autoinducers of ''RNAIII'' is RAP (''RNAIII'' activating protein) and the ''arg''- encoded ''AIPs'' (autoinducing peptides) ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 13]).
 +
 
 +
=Quorum-quenching using ''RIP''=
 +
 
 +
[[Image:Image-SDU-Denmark-RIP.jpg|300px|thumb|right|Figure 6. Schematic drawing of ''RIP''s inhibiting function on ''S. aureus''. RIP: RNAIII inhibiting peptide; RAP: RNAIII  activating peptide; TRAP: target of RAP.]]
 +
 
 +
The ability to disrupt quorum sensing is known as Quorum-quenching.
 +
 
 +
Quorum-quenching has a great therapeutic potential, since interfering with the bacterial communication can prevent colonization of specific pathogen bacteria that use quorum sensing to coordinate virulence ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 10]).
 +
 
 +
''RNAIII'' synthesis can be inhibited by different mechanisms. The most potent inhibition is seen by the ''RNAIII inhibiting peptide (RIP)''.  This peptide is produced by coagulase negative staphylococcus, ''S. warnerii'' and ''S. xylosus. ''RIP'' has the sequence YSPXTNF, where X can be a cysteine, a tryptophan, or a modified
 +
amino acid.
 +
 
 +
Native ''RIP'' and a synthetic analogue YSPWTHF have been shown effective in inhibiting ''RNAIII'' synthesis ''in vitro'' and ''S.aureus'' infections ''in vivo'' ([https://2009.igem.org/Team:SDU-Denmark/Background#Literature 10]).
 +
 
 +
=Literature=
 +
 
 +
1. [http://www.denstoredanske.dk/Krop,_psyke_og_sundhed/Sundhedsvidenskab/Farmakologi/penicillin Penicillin; Den store Danske Encyklopædi; 2009].
 +
 
 +
2. [http://cmr.asm.org/cgi/reprint/10/3/505?view=long&pmid=9227864 Kluytmans J et al; Carriage of Staphylococcus aureus: Epidemiology, Underlying Mechanisms, and Associated Risks; Clinical Microbiology Reviews; Vol. 10, No. 3 1997].
 +
 
 +
3. Højby N and Skinhøj P; Klinisk Mikrobiologi og Infektionsmdicin; 3.th edition 1st issue 2008.
 +
 
 +
4. [http://www.journals.uchicago.edu/doi/abs/10.1086/520289 Archer GL; Staphylococcus aureus: A Well‐Armed Pathogen; Clinical Infectious Diseases 1998;26:1179–1181].
 +
 
 +
5. [http://www.medicinenet.com/staph_infection/article.htm Staph Infection on medicinenet.com].
 +
 
 +
6. [http://scmsociety.typepad.com/mrsa/mrsa-patient-information.html Image from scmssociety.typepad.com].
 +
 
 +
7. [http://en.wikipedia.org/wiki/MRSA Wikipedia, MRSA].
 +
 
 +
8. Klevens et. al; Journal of the American Medical Association 1997; 298 (15);1763-1771
 +
 
 +
9. Madigan  MT and Martinko JM; BROCK BIOLOGY OF MICROORGANISMS, Eleventh edition. 2006. Pearson Prentice Hall. USA
 +
 
 +
10. Balaban N et al; Regulation of ''S. aureus'' pathogenesis via TRAP; JBC Papers in Press. Published on October 16, 2000 as Manuscript M005446200]]
 +
 
 +
11. [http://en.wikipedia.org/wiki/File:Staphylococcus_aureus_biofilm_01.jpg Image from Wikipedia].
 +
 
 +
12. JYarwood JM, Bartels DJ, Volper EM and Greenberg EP. Quorum Sensing in Staphylococcus aureus Biofilms;  Department of Microbiology, Roy and Lucille Carver College of Medicine, University of Iowa, Received 21 October 2003/Accepted 1 December 2003
 +
 
 +
13. Waters CM and Bassler BL; Quorum Sensing: Cell-to-Cell Communication in Bacteria; Department of Molecular Biology, Princeton University, Princeton, New Jersey.
 +
 
 +
 
 +
 
 +
 
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==''S. aureus''==
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''S. aureus'' is one of the largest causes of hospital infections, each year infecting millions of people around the globe.
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''S. aureus'' is normally commensal, but can create bacterial biofilms on implanted medical devices and in post-operational wounds. Biofilm is becoming increasingly hard to treat, as a result of growing resistance to many types of antibiotics.
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==Brainstorm==
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Before we decided to work on this project, we had a bunch of other great ideas. You can check out our initial [[Team:SDU-Denmark/Brainstorm|brainstorm here]].
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==Content==
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__TOC__
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Latest revision as of 00:01, 22 October 2009







Description of S. aureus

Figure 1. S. aureus, colored.

Staphylococcus aureus, also known as golden staph, is the most common cause of staphylococcus infections. It is a gram positive bacterium, that normally can be treated with penicillin. Unfortunately they are becoming more and more resistant to common antibiotics and thereby harder to treat ([http://www.denstoredanske.dk/Krop,_psyke_og_sundhed/Sundhedsvidenskab/Farmakologi/penicillin 1]).

The nose is regarded as the major site of S. aureus infection and from there the organisms can spread to other parts of the body. About 20% of the human population are long-term carriers of S. aureus. Frequently part of the skin flora is contaminated ([http://cmr.asm.org/cgi/reprint/10/3/505?view=long&pmid=9227864 2]).

Transmission of S. aureus to surgical wound via the skin in patients who are nasal carriers could be an explanation for endogenous infection. Preoperative disinfection is not as effective in the deeper layers of the skin, and S. aureus may thus become a source of infection during surgery ([http://cmr.asm.org/cgi/reprint/10/3/505?view=long&pmid=9227864 2]).

The ability to control staphylococcal infections in the future will depend on many factors, e.g., development of new therapeutic agents, optimization of infection control measures, and introduction of new medical devices with a reduced risk of infection ([http://cmr.asm.org/cgi/reprint/10/3/505?view=long&pmid=9227864 2]).

Pathogenesis

Figure 2. Scalded skin syndrome. From Dennis Kunkel, Microscopy Inc.
‎
Figure 3. Abscess. [http://scmsociety.typepad.com/mrsa/mrsa-patient-information.html (6)]

S. aureus is considered a opportunistic pathogen as it can cause infections, while at the same time being part of the normal flora. S. aureus is currently the most common cause of infections in hospitalized patients, with postoperative wound infections being an especially big problem (3).

The success of S. aureus as a pathogen, and its ability to cause such a wide range of infections, are the result of its extensive virulence factors such as toxins ([http://www.journals.uchicago.edu/doi/abs/10.1086/520289 4], [http://www.medicinenet.com/staph_infection/article.htm 5]).

S. aureus infections are plentiful and diverse. The most common infection is of the skin as impertigo, cellulitis or less frequent scalded skin syndrome ([http://www.medicinenet.com/staph_infection/article.htm 5]).

If the bacteria enters the bloodstream, a condition known as sepsis, the bacteria can spread to organs with many serious complications, death often being the result (3).

MRSA

Methicillin-resistant Staphylococcus Aureus (MRSA) is defined as a strain of S. aureus that is resistent to beta-lactam antibiotics, which includes common drugs such as penicillins and the cephalosporins ([http://en.wikipedia.org/wiki/MRSA 7]).

MRSA can cause the same serious infections as other strains of S. aureus, but is especially troublesome, because of it's resistance to the most common antibiotics.

In the United States, invasive (i.e., serious) "MRSA" infections occur in approximately 94,000 persons each year and are associated with approximately 19,000 deaths (8).

Several antibiotics with the ability to kill S. aureus have been made, such as vancomycin and teicoplanin, both drugs that are used to treat MRSA infections today. The absorption of these drugs is very low, for which reason it has to be administrated intravenously. This administration route is not optimal. Moreover new strains has been discovered that are resistant to vancomycin, called VRSA (vancomycin-resistant Staphylococcus aureus) ([http://en.wikipedia.org/wiki/MRSA 7]).

To be able to treat patients with S. aureus infections in the future, new antibiotics and new methods of treatment most be found.

Biofilm Formation

S. aureus pathogenecity depends on quorum-sensing and biofilm formation. Biofilm is a layer of microbes embedded in an extracellular slime/adhesive, usually polysaccharide material excreted by the cells and attached to a surface (9).

A biofilm facilitates a microenvironment suited for the bacteria. It improves adhesion to the host; it protects the bacteria from hostile environments; and it may confer relative resistance by shielding the bacteria from antibiotics.

S. aureus biofilm formation depends on two quorum-sensing systems, leading to expression of RNAIII that regulates expression of genes involved in pathogenesis. Other staphylococcus strains have developed a RNAIII-inhibiting peptide (RIP) that quenches quorum-sensing, and reduces RNAIII transcription and biofilm formation in S. aureus (10).

Figure 4. The five stages of bacterial biofilm formation. (A) Bacteria reversibly attach to solid support. (B) Bacteria become irreversibly attached, and aggregate to form matrix. (C) Maturation phase: cells become layered and effects of quorum sensing begin. (D) Clusters reach maximum thickness. (E) Escape of planktonic bacteria from matrix dispersion. From Slimy business — the biotechnology of biofilms; Nature 21, 361 - 365 (2003)
Figure 5. S.aureus biofilm [http://en.wikipedia.org/wiki/File:Staphylococcus_aureus_biofilm_01.jpg (11)]


Quorum-sensing

Quorum-sensing bacteria produce molecules, termed autoinducers, that function as chemical signal molecules. The concentration of these signals increase as a function of the number of cells in a colony. Using this chemical signaling, the bacteria can adapt to the current situation, and like a multicellular organism synchronize their behavior. The colony of bacteria forms biofilms, that are sessile microbial communities embedded in a self-produced extracellular polymeric matrix, with the advantages described above (12).

The strategy is that bacteria at a low level will express protein factors that promote attachment and colonization, whereas they at lager scale will repress these genes and instead express genes of toxins and proteases, factors that are required for dissemination (13).

In S. aureus the genes involved in quorum-sensing are encoded by the agr-locus (accessory gene regulator) system (12).

Two different promoters P2 and P3 drive the two operons of the arg-locus. The P2 operon codes for a RNAII transcript, while the P3 promoter drives transcription of RNAIII. RNAIII is an important part of the system as it regulates at least 15 genes coding for potential virulence factors (13).

The synthesis of RNAIII is regulated by quorum-sensing molecules. When the autoinducers of the system reach a threshold concentration RNAIII is synthesized. The described autoinducers of RNAIII is RAP (RNAIII activating protein) and the arg- encoded AIPs (autoinducing peptides) (13).

Quorum-quenching using RIP

Figure 6. Schematic drawing of RIPs inhibiting function on S. aureus. RIP: RNAIII inhibiting peptide; RAP: RNAIII activating peptide; TRAP: target of RAP.

The ability to disrupt quorum sensing is known as Quorum-quenching.

Quorum-quenching has a great therapeutic potential, since interfering with the bacterial communication can prevent colonization of specific pathogen bacteria that use quorum sensing to coordinate virulence (10).

RNAIII synthesis can be inhibited by different mechanisms. The most potent inhibition is seen by the RNAIII inhibiting peptide (RIP). This peptide is produced by coagulase negative staphylococcus, S. warnerii and S. xylosus. RIP has the sequence YSPXTNF, where X can be a cysteine, a tryptophan, or a modified amino acid.

Native RIP and a synthetic analogue YSPWTHF have been shown effective in inhibiting RNAIII synthesis in vitro and S.aureus infections in vivo (10).

Literature

1. [http://www.denstoredanske.dk/Krop,_psyke_og_sundhed/Sundhedsvidenskab/Farmakologi/penicillin Penicillin; Den store Danske Encyklopædi; 2009].

2. [http://cmr.asm.org/cgi/reprint/10/3/505?view=long&pmid=9227864 Kluytmans J et al; Carriage of Staphylococcus aureus: Epidemiology, Underlying Mechanisms, and Associated Risks; Clinical Microbiology Reviews; Vol. 10, No. 3 1997].

3. Højby N and Skinhøj P; Klinisk Mikrobiologi og Infektionsmdicin; 3.th edition 1st issue 2008.

4. [http://www.journals.uchicago.edu/doi/abs/10.1086/520289 Archer GL; Staphylococcus aureus: A Well‐Armed Pathogen; Clinical Infectious Diseases 1998;26:1179–1181].

5. [http://www.medicinenet.com/staph_infection/article.htm Staph Infection on medicinenet.com].

6. [http://scmsociety.typepad.com/mrsa/mrsa-patient-information.html Image from scmssociety.typepad.com].

7. [http://en.wikipedia.org/wiki/MRSA Wikipedia, MRSA].

8. Klevens et. al; Journal of the American Medical Association 1997; 298 (15);1763-1771

9. Madigan MT and Martinko JM; BROCK BIOLOGY OF MICROORGANISMS, Eleventh edition. 2006. Pearson Prentice Hall. USA

10. Balaban N et al; Regulation of S. aureus pathogenesis via TRAP; JBC Papers in Press. Published on October 16, 2000 as Manuscript M005446200]]

11. [http://en.wikipedia.org/wiki/File:Staphylococcus_aureus_biofilm_01.jpg Image from Wikipedia].

12. JYarwood JM, Bartels DJ, Volper EM and Greenberg EP. Quorum Sensing in Staphylococcus aureus Biofilms; Department of Microbiology, Roy and Lucille Carver College of Medicine, University of Iowa, Received 21 October 2003/Accepted 1 December 2003

13. Waters CM and Bassler BL; Quorum Sensing: Cell-to-Cell Communication in Bacteria; Department of Molecular Biology, Princeton University, Princeton, New Jersey.



S. aureus

S. aureus is one of the largest causes of hospital infections, each year infecting millions of people around the globe.

S. aureus is normally commensal, but can create bacterial biofilms on implanted medical devices and in post-operational wounds. Biofilm is becoming increasingly hard to treat, as a result of growing resistance to many types of antibiotics.

Brainstorm

Before we decided to work on this project, we had a bunch of other great ideas. You can check out our initial brainstorm here.

Content

Contents



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