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Genetic basis of glycopeptide resistance in staphylococci

Applicant Berger-Bächi Brigitte
Number 63201
Funding scheme NRP 49 Antibiotic resistance
Research institution Institut für Medizinische Mikrobiologie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Medical Microbiology
Start/End 01.01.2002 - 31.08.2005
Approved amount 350'094.00
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Lay Summary (English)

Lead
Lay summary
Genetic basis of glycopeptide resistance in staphylococci

In the view of the growing antibiotic resistance in bacteria causing infections, it is of utmost importance to preserve the efficacy of the existing antibiotics and to develop new strategies to combat antibiotic resistance formation and spread. Newly emerging resistance mechanisms, such as low-level glycopeptide resistance in staphylococci, need to be studied and understood on all levels, starting from the genome and the genes, which are the coding for the resistance, to the properties of the resistant strain, such as alterations in virulence and epidemiology. Only with such a comprehensive knowledge we will be able to combat efficiently the threat of multiresistant pathogens, which could bring us back into the preantibiotic era.

Background
Staphylococci are intimately involved with our life and are the most common human pathogens causing community-acquired
and nosocomial infections. They have the remarkable ability to become resistant to many different antibiotics and therefore are
becoming more and more difficult to therapy. Some strains of Stapyhlococcus aureus resistant to glycopeptides have emerged
recently, making last class of antibiotics against multiresistant S. aureus obsolete. Although of low level-resistance, these
strains, called intermediate vancomycin resistant Staphylococcus aureus (VISA), can cause glycopeptide therapy failure,
especially in patients with persistent infections. The experimental identification of VISA by the diagnostic laboratory is difficult
because of the very small difference in resistance between susceptible and resistant strains. VISA are often recognized only
after glycopeptide therapy failure.

Aim
We are studying the different ways staphylococci adopt to acquire this low level vancomycin resistance. By comparing the differences between susceptible and resistant strains, and by looking how they behave when treated with antibiotics, we can identify the genes that are important for developing glycopeptide resistance. Our goal is to find new means or strategies to prevent resistance development, and rapid methods to identify strains with predisposition to glycopeptide resistance formation, so that measures can be taken to prevent their spread. During our seach for important traits indicative of glycopeptide resistance we hope to identify the weak point of the bacteria that could be used as new target for antibacterial agents.

Significance
These studies have impact on the health and wellbeing of the people at risk of staphylococcal infection, such as the growing number of immunocompromised patients, carriers of prosthetic devices, and the increasing number of the aging population. These studies are part of the efforts required to preserve the efficacy of the existing antibiotics and to prevent the emergence and spread of multiresistant strains, which in the near future can not be treated any more by the existing antibiotic choice.
Direct link to Lay Summary Last update: 21.02.2013

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