Antibiotic resistance: it's bad, but why isn't it worse?

Abstract

Antibiotic natural products are ancient and so is resistance. Consequently, environmental bacteria harbor numerous and varied antibiotic resistance elements. Nevertheless, despite long histories of antibiotic production and exposure, environmental bacteria are not resistant to all known antibiotics. This means that there are barriers to the acquisition of a complete resistance armamentarium. The sources, distribution, and movement of resistance mechanisms in different microbes and bacterial populations are mosaic features that act as barriers to slow this movement, thus moderating the emergence of bacterial pan-resistance. This is highly relevant to understanding the emergence of resistance in pathogenic bacteria that can inform better antibiotic management practices and influence new drug discovery.

Fig. 1

Past and present cycles of antibiotic discovery and resistance. For approximately 70 years (1930s–1990s) pathogenic bacteria and the diseases they cause were controlled with the discovery of many new antibiotic scaffolds and derivatives. Resistance inevitably emerged, by the capture of mobile resistance elements or intrinsic mechanisms, but was countered with new drug discovery. In the present situation, the lack of new antibiotic drugs and the rise of multi-drug-resistant pathogens that harbor many resistance elements presents a grave public health challenge

Fig. 2

Gentamicin resistance, an example of genetic and biochemical diversity. Resistance to gentamicin occurs in a variety of ways. Altered membrane potential, efflux, and 16S rRNA methylation all confer resistance but leave the antibiotic unaltered. Various group-transfer reactions add phosphoryl, nucleotidyl, or acetyl groups at several positions on the molecule