Antibiotic resistance: an overview of mechanisms and a paradigm shift

Antibiotic resistance is the biggest challenge to the medical profession in the treatment of infectious diseases. Resistance has been documented not only against antibiotics of natural and semi-synthetic origin, but also against purely synthetic compounds (such as the fluoroquinolones) or those which do not even enter the cells (such as vancomycin). The wide range of occurrence of antibiotic resistance suggests that, in principle, any organism could develop resistance to any antibiotic. The phenomenon of horizontal gene transfer compounds the problem by facilitating rapid spread of antibiotic resistance. Unfortunately, the discovery and development of newer antibiotics have not kept pace with the emergence of antibiotic resistance. In this article a broad overview of the various mechanisms of antibiotic resistance will be presented mainly to illustrate their variety, rather than to catalogue everything that is known. Of late, a paradigm shift in the traditional perception of antibiotics and antibiotic resistance is emerging. Antibiotics are beginning to be viewed as intermicrobial signalling agents and even as sources of nutrition to microorganisms, rather than as weapons in the hands of antibiotic producer organisms to fight against competitors which might cohabit with them. Likewise, mechanisms of antibiotic resistance are being believed to have evolved not as defence strategies which microbes use to thwart the action of antibiotics, but as integral components of processes involved in basic bacterial physiology. However, when these mechanisms get placed out of their natural context their resistance property alone gets highlighted. Many leading workers in the field call this emerging trend of thought as a Copernican turning point. Some of these trends will be discussed towards the end.