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 lab 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.
This is one of a series of articles commissioned and edited by the TB
Alliance and published in a special issue of Tuberculosis, entitled
'Key issues in TB drug research and development'.
Tuberculosis (2008) 88, Supplement 1, S25-33 [doi:10.1016/S1472-9792(08)70034-9]
A philosophy of anti-infectives as a guide in the search for new drugs for tuberculosis