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Tracking the evolution of methicilin resistance in staphylococci: stages in the evolution of the mecA determinant and the SCCmec structure

Instituto de Tecnologia Química e Biológica
Project classification

Scientific area

1.6 Biological sciences (Medical sciences go to scientific area 3.n; Agricultural sciences go to scientific area 4.n)

Discipline(s)

Evolutionary biology

Project description

Project title

Tracking the evolution of methicilin resistance in staphylococci: stages in the evolution of the mecA determinant and the SCCmec structure

Scientific Coordinator's name:

Maria Miragaia

Scientific Coordinator's e-mail:

miragaia@itqb.unl.pt

Principal R&D Unit:

Instituto de Tecnologia Química e Biológica (ITQB)

Other R&D Units involved in the project:

The Rockefeller University

Project keyword(s)

methicillin resistance, evolution, Staphylococcus, mecA, staphylococcal cassette chromosome mec (SCCmec)

Short abstract and comments

One of the top public health concerns of our era is antibiotic resistance which limits the therapeutic choices available to treat bacterial infections. Thus, a better understanding of evolutionary processes that lead to the emergence of antibiotic resistance is of crucial importance. The purpose of this research proposal is to identify stages in the evolution of wide spectrum beta-lactam resistance of staphylococci, major causative agents of both hospital and community acquired infections. All methicillin resistant S. aureus (MRSA) carries the acquired gene mecA on a structurally complex mobile genetic element called staphylococcal chromosome cassette mec (SCCmec). SCCmec is composed of two central building blocks: the mec complex (the mecA gene and its regulators) and the ccr complex which is responsible for its mobility and dissemination among staphylococci. The origin of the mecA gene was tentatively identified as a ubiquitous housekeeping gene in Staphylococcus sciuri - a primitive Staphylococcus species, that colonizes the skin of humans and both domestic and wild animals. SCCmec evolution is believed to have occurred in several steps involving several staphylococcal species. A number of steps are still missing in the evolutionary history of this element. The purpose of this research proposal is to better understand the origin and identify stages in the evolution of SCCmec. We plan to investigate (i) how and when did the mecA gene homologue native to S. sciuri evolve into a resistant determinant; (ii) how and in what species were the mecA regulators added to the mec complex; (iii) how was the native S. sciuri mecA mobilized “out of S. sciuri” into other staphylococci; (iv) in which stage of evolution did the SCCmec become mobile; (v) and if there are single or several alternative pathways for SCCmec evolution.

Potential uses/indications

The successful use of antimicrobial agents is relentlessly compromised by the potential development of tolerance or resistance. We hope that the knowledge produced by this project will help to identify the genetic processes involved in the emergence and dissemination of resistance to beta-lactams. We expect to produce data that will contribute in the future to improve an effective prevention and control of resistance development.

Status

Ongoing

Partner Status: Seeking Partners?

No

Project weblink

http://Not applicable

Grant number (QREN, FP7, Eureka, etc)

PTDC/BIA-EVF/117507/2010

Last edited on

2012-10-03 11:43:50

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