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.
Keywords: B vitamins, co-factor starvation, drug discovery, MRSA, multi drug resistance, pro-drug, suicide drug.
Current Medicinal Chemistry
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:
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.
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Cite this article as:
Drebes Julia, Kunz Madeleine, Pereira A. Claudio, Betzel Christian and Wrenger Carsten, MRSA Infections: From Classical Treatment to Suicide Drugs, Current Medicinal Chemistry 2014; 21 (15) . https://dx.doi.org/10.2174/0929867320666131119122520
DOI https://dx.doi.org/10.2174/0929867320666131119122520 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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