MRSA Infections: From Classical Treatment to Suicide Drugs

DREBES, JULIA; KÜNZ, MADELEINE; PEREIRA, CA; BETZEL, CHRISTIAN; WRENGER, CARSTEN

CURRENT MEDICINAL CHEMISTRY.

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2014 vol. 21 p. 1809 - 1819

0929-8673

Infections caused by the methicillin-resistant Staphylococcus aureus (MRSA) are today a major 16 burden in nosocomial disease control. The global trend shows an alarming increase of MRSA infections as well 17 as multi-drug resistance (MDR). The problem is exacerbated by the fact that infections with community-18 associated (CA) MRSA strains showing increased virulence and fitness add to infections with multi-drug 19 resistant hospital-associated (HA) MRSA. The toxicity of pathogens and limited effectiveness of available 20 treatment have led to high mortality rates and vast expenses caused by prolonged hospitalization and usage of 21 additional antibiotics. Recently approved drugs still have classical targets and upcoming resistance can be 22 expected. In a new approach by targeting co-factor syntheses of bacteria, the drug target and the affected 23 pathways are uncoupled. This novel strategy is based on the thought of a classical pro-drug which has to be 24 metabolized before becoming toxic for the bacterium as a dysfunctional co-factor, named suicide drug. Ideally 25 these metabolizing pathways are solely present in the bacterium and absent in the human host, such as vitamin 26 biosyntheses. This mini-review discusses current ways of MRSA infection treatment using new approaches 27 including suicide drugs targeting co-factor biosyntheses.