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Molecular and genetic basis of methicillin resistance in Staphylococcus aureus

English title Molecular and genetic basis of methicillin resistance in Staphylococcus aureus
Applicant Berger-Bächi Brigitte
Number 105390
Funding scheme Project funding (Div. I-III)
Research institution Institut für Medizinische Mikrobiologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Medical Microbiology
Start/End 01.11.2004 - 31.10.2007
Approved amount 335'000.00
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Keywords (5)

Staphylococcus aureus; cell wall synthesis; methicillin resistance; global regulation; fitness

Lay Summary (English)

Lead
Lay summary
Methicillin resistant Staphylococcus aureus (MRSA) are still gaining infrequency and importance as nosocomial and community aquired pathogens.They are problem, especially in hospitals, because of their resistance toall beta-lactam antibiotics and their remarkable ability to acquireadditional resistance mechanims in the presence of antibiotic pressure.The recent emergence of new, more virulent community-onset MRSA isdisturbing, especially if they go on to acquire multiresistance as well.In order to have better control over MRSA we intend to identify new lethaltargets for novel antibacterial agents, and to find new ways to combatthis pathogen. We have to know more about its way of life, how it developsresistance and regulates its virulence.
1. The bacterial cell wall is an excellent target for antibacterialagents. Many components involved in its synthesis are unknown and mayserve as antibacterial targets. Synthesis of the characteristicpentaglycine interpeptide which crosslinks the staphylococcal cell wall isimportant for methicillin resistance. We are therefore investigating themechanism and factors involved in its synthesis and their effect onmethicilln resistance. By genetic manipulations and reconstituting cellwall synthesis in vitro, we plan to characterize how Lif and Epr, twononribosomal peptidyltransferases, integrate serine residues into thisinterpeptide.
2. Methicillin resistance has many faces. MRSA can appear as highlyresistant- or as apparently susceptible strains. Neither the genetic andbiochemical differences between high and low level resistant strains northeir impact on bacterial metabolism or host bacterial interactions areknown. We will determine by microarrays the metabolic characteristics ofhigh versus low level methicillin resistance in isogenic strain pairs. Wewill analyse in particular the apparent correlation between high levelresistance and decreased growth rates and vice versa, in order to learnmore about staphylococcal metabolism and regulation of methicillinresistance levels. Genes involved in global, and carbon metabolismregulation, will be investigated in more detail.
3. A low level resistant MRSA clone is spreading amongst drug addicts inZürich, which may be mistaken for a susceptible S. aureus. By knowing moreabout its particularities and the epidemiology of the MRSA ocurring in ourregion, we will follow its evolution and possible dissemination. We willanalyse its potential to develop into a highly resistant MRSA and theresulting possible impact on its fitness.

Our studies aim at improving the health and quality of life of people atrisk of S. aureus infections, such as the immunocompromised, elderly andvery young, carriers of indwelling devices, and that of hospitalised andnursing home patients.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
117707 Genetic and molecular basis of methicillin and glycopeptide resistance in Staphylococcus aureus 01.11.2007 Project funding (Div. I-III)
63552 Genetic and molecular basis of methicillin and glycopeptide resistance in Staphylococcus aureus 01.09.2001 Project funding (Div. I-III)

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