A philosophy of anti-infectives as a guide in the search for new drugs for tuberculosis

作者：Nathan Carl^*; Gold Ben; Lin Gang; Stegman Melanie; de Carvalho Luiz Pedro Sorio; Vandal Omar; Venugopal Aditya; Bryk Ruslana

来源：Tuberculosis, 2008, 88: S25-S33.

DOI：10.1016/S1472-9792(08)70034-9

• acid
• dihydrolipoamide acyltransferase
• lipoamide dehydrogenase
• nitric oxide
• mycobacterium
• nucleotide excision repair
• protease
• proteasome
• tuberculosis

How we develop antibiotics is shaped by how we view infectious disease. Given the urgent need for new chemotherapeutics for tuberculosis and other infectious diseases, it is timely to reconsider a view of infectious disease that is strongly supported by contemporary evidence but that has rarely been applied in antibiotic development. This view recognizes the importance of nonreplicating bacteria in persistent infections, acknowledges the heterogeneity and stringency of chemical environments encountered by the pathogen in the host, and emphasizes metabolic adaptation of the host and the pathogen during their competition. For example, efforts in our tab are guided by the perspective that Mycobacterium tuberculosis (Mtb) has co-evolved with the human immune response, with the result that Mtb turns host-imposed metabolic adversity to its own advantage. We seek chemotherapeutics that turn Mtb's adversity to the host's advantage.

• 出版日期2008-8