期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：38
DOI：10.1073/pnas.2205407119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Antibiotics, like penicillin, treat a wide range of infections. This broad-spectrum of activity has its evolutionary roots in microbial warfare, where antibiotics can provide a competitive edge. But bacteria also make narrow-spectrum toxins, which presents a puzzle: Why not use broad-spectrum toxins to target more competitors? Using evolutionary modelling, we show that narrow-spectrum toxins help focus an attack on a key competitor, minimizing toxin loss to other targets. Broad-spectrum attacks only make sense when a microbe is abundant and can make a lot of toxin. We survey available data and find, as predicted, that broad-spectrum toxins are typically made by bacteria at high abundance. This suggests that antibiotics evolved in dominant microbes that could afford to take on diverse competitors.
A key property of many antibiotics is that they will kill or inhibit a diverse range of microbial species. This broad-spectrum of activity has its evolutionary roots in ecological competition, whereby bacteria and other microbes use antibiotics to suppress other strains and species. However, many bacteria also use narrow-spectrum toxins, such as bacteriocins, that principally target conspecifics. Why has such a diversity in spectrum evolved? Here, we develop an evolutionary model to understand antimicrobial spectrum. Our first model recapitulates the intuition that broad-spectrum is best, because it enables a microbe to kill a wider diversity of competitors. However, this model neglects an important property of antimicrobials: They are commonly bound, sequestered, or degraded by the cells they target. Incorporating this toxin loss reveals a major advantage to narrow-spectrum toxins: They target the strongest ecological competitor and avoid being used up on less important species. Why then would broad-spectrum toxins ever evolve? Our model predicts that broad-spectrum toxins will be favored by natural selection if a strain is highly abundant and can overpower both its key competitor and other species. We test this prediction by compiling and analyzing a database of the regulation and spectrum of toxins used in inter-bacterial competition. This analysis reveals a strong association between broad-spectrum toxins and density-dependent regulation, indicating that they are indeed used when strains are abundant. Our work provides a rationale for why bacteria commonly evolve narrow-spectrum toxins such as bacteriocins and suggests that the evolution of antibiotics proper is a signature of ecological dominance.
