Selection and Transmission of Antibiotic-Resistant Bacteria

Abstract

Ever since antibiotics were introduced into human and veterinary medicine to treat and prevent bacterial infections there has been a steady selection and increase in the frequency of antibiotic resistant bacteria. To be able to reduce the rate of resistance evolution, we need to understand how various biotic and abiotic factors interact to drive the complex processes of resistance emergence and transmission. We describe several of the fundamental factors that underlay resistance evolution, including rates and niches of emergence and persistence of resistant bacteria, time- and space-gradients of various selective agents, and rates and routes of transmission of resistant bacteria between humans, animals and other environments. Furthermore, we discuss the options available to reduce the rate of resistance evolution and/ or transmission and their advantages and disadvantages.

Keywords: SOS; antibiotic resistance; conjugation; horizontal gene transfer; mobile genetic elements; mutation rates; selection; successful clones; transmission.

FIGURE 1

Schematic view of the evolution of antibiotic resistance. Key questions in understanding the emergence and transmission include: (A) What are the origins of resistance genes? (B) Where do resistant pathogens emerge? (C) Which are the most significant selective pressures driving resistance evolution? (D) Which are the biological factors that influence rates of resistance development? (E) What are the routes, directions, and magnitudes of flow of pathogens between humans, animals, and the environment?

FIGURE 2

Selection for antibiotic resistance occurs at several levels of complexity to generate a successful resistant clone.

FIGURE 3

Effects of antibiotics on HGT and potential inhibition points.

FIGURE 4

Generic scheme for the creation and spread of globally successful antibiotic-resistant clones. In all environments (human, animal, and the wider environment), there are bacterial variants with resistance plasmids, resistance mutations, resistance genes, virulence genes, genes that increase transmission, etc. The mechanisms of HGT, coupled with selection by use of antibiotics, can select for combinations of these elements in one clone. When a clone arises that combines clinical resistance with high fitness and transmissibility, such a clone can spread through the global human population and become a dominant successful clone such as ST131 or ST258.