Title:MRSA Infections: From Classical Treatment to Suicide Drugs
VOLUME: 21 ISSUE: 15
Author(s):Julia Drebes, Madeleine Kunz, Claudio A. Pereira, Christian Betzel and Carsten Wrenger
Affiliation:Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil.
Keywords:B vitamins, co-factor starvation, drug discovery, MRSA, multi drug resistance, pro-drug, suicide drug.
Abstract:Infections caused by the methicillin-resistant Staphylococcus aureus (MRSA) are today a major burden in
nosocomial disease control. The global trend shows an alarming increase of MRSA infections as well as multi-drug resistance
(MDR). The problem is exacerbated by the fact that infections with community-associated (CA) MRSA strains
showing increased virulence and fitness add to infections with multi-drug resistant hospital-associated (HA) MRSA. The
toxicity of pathogens and limited effectiveness of available treatment have led to high mortality rates and vast expenses
caused by prolonged hospitalization and usage of additional antibiotics. Recently approved drugs still have classical targets
and upcoming resistance can be expected. In a new approach by targeting co-factor syntheses of bacteria, the drug
target and the affected pathways are uncoupled. This novel strategy is based on the thought of a classical pro-drug which
has to be metabolized before becoming toxic for the bacterium as a dysfunctional co-factor, named suicide drug. Ideally
these metabolizing pathways are solely present in the bacterium and absent in the human host, such as vitamin biosyntheses.
This mini-review discusses current ways of MRSA infection treatment using new approaches including suicide drugs
targeting co-factor biosyntheses.
