Persister-mediated emergence of antimicrobial resistance in agriculture due to antibiotic growth promoters

Abstract

The creation and continued development of antibiotics have revolutionized human health and disease for the past century. The emergence of antimicrobial resistance represents a major threat to human health, and practices that contribute to the development of this threat need to be addressed. Since the 1950s, antibiotics have been used in low doses to increase growth and decrease the feed requirement of animal-derived food sources. A consequence of this practice is the accelerated emergence of antimicrobial resistance that can influence human health through its distribution via animal food products. In the laboratory setting, sublethal doses of antibiotics promote the expansion of bacterial persister populations, a low energy, low metabolism phenotype characterized broadly by antibiotic tolerance. Furthermore, the induction of persister bacteria has been positively correlated with an increased emergence of antibiotic-resistant strains. This body of evidence suggests that the use of antibiotics in agriculture at subtherapeutic levels is actively catalyzing the emergence of antimicrobial-resistant bacteria through the expansion of bacterial persister populations, which is potentially leading to increased infections in humans and decreased antibiotic potency. There is an urgent need to address this debilitating effect on antibiotics and its influence on human health. In this review, we summarize the recent literature on the topic of emerging antimicrobial resistance and its association with bacterial persister populations.

Keywords: agriculture; antibiotic growth promoters; antibiotics; antimicrobial resistance; bacteria; catalyze; persistence; resistance; subtherapeutic; tolerance.

Figure 1:. Two different models of viewing the emergence of antibiotic-resistant bacteria in agriculture. The "survival of the fittest" model (A) demonstrates the passive emergence of resistant bacteria as an innate feature of antibiotic use. The "AGP catalysis” model (B) demonstrates the active induction of resistant bacteria through AGP use.

Created with BioRender.com

Figure 2:. Countermeasures against the catalysis of antibiotic-resistant bacteria by AGPs. (A) The restriction of certain classes of antibiotics to specific sectors would reduce the overlap of commonly used antibiotics and decrease future recalcitrant diseases. (B) The development and implementation of nonantibiotic growth promoters would decrease selective pressure for resistant bacteria ,. (C) Specific killing of persister populations would decrease the time and quantity of bacteria that AGPs can exert selective pressure on, resulting in a decreased emergence of resistant bacteria.

Created with BioRender.com