Where have All the Antibiotics Gone?

Abstract

The discovery of antibiotics some 60 years ago was anticipated to herald the end of infectious diseases. However, microbial evolution and genetic jugglery have dispelled this notion; the constant increase in the appearance of resistant strains has not been matched by the introduction of new therapeutic agents. On the contrary, the dire need for novel antibiotics has coincided with a reduction in antibiotic discovery programs in the pharmaceutical industry. As a result, the treatment of microbial diseases has reached a point where many infections are essentially untreatable by the antimicrobial agents currently available. At the present time, numerous initiatives are being undertaken by physicians and by governments in an attempt to redress this situation. In addition, alternative approaches to antibiotics for the treatment of infectious diseases are being explored intensively.

Keywords: Alternative therapies; Antibiotic resistance; Mechanisms.

Figure 1

The process of resistance gene capture by an integron. The genetic structure of the basic type I integron is shown at the top of the figure. P_ant is the promoter that transcribes any gene sequence inserted at the attachment site (attI). The resistance gene cassette (middle) is inserted into the integron structure as a result by recombination between the attC and attI sequences catalyzed by the integrase (intI1 gene). Once integrated, the resistance gene is expressed. Multiple antibiotic resistance occurs by the insertion of additional resistance gene cassettes at the attI site. sul1 encodes resistance to sulfonamide drugs, and gacEΔ is a defective export system. The latter two are found on all type I integrons. This figure was kindly provided by Dr Patrice Courvalin (Institut Pasteur, Paris, personal communication)

Figure 2

The interactive network of pathogens and antibiotic resistance genes