School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia.
Environ Microbiol Rep. 2017 Oct;9(5):635-641. doi: 10.1111/1758-2229.12564. Epub 2017 Jul 13.
The relationship between bacterial drug resistance and growth fitness is a contentious topic, but some antibiotic resistance mutations clearly have a fitness cost in the laboratory. Whether these costs translate into deleterious effects in natural habitats is less certain however. Previously, fitness effects of resistance mutations were mostly characterized in nutrient-rich, fast-growth conditions, which bacteria rarely encounter in natural habitats. Carbon, phosphate, iron or oxygen limitations are conditions met by bacterial pathogens in various compartments of the human body. Here, we measured the fitness of four different rpoB mutations commonly found in rifampicin-resistant bacterial isolates. The fitness properties and the emergence of these and other alleles were studied in Escherichia coli populations growing under nutrient excess and in four different nutrient-limited states. Consistent with previous findings, all four mutations exhibited deleterious fitness effects under nutrient-rich conditions. In stark contrast, we found positive or neutral fitness effects under nutrient-limited conditions. Two particular rpoB alleles had a remarkable fitness increase under phosphate limitation and these alleles arose to high frequencies specifically under phosphate limitation. These findings suggest that it is not meaningful to draw general conclusions on fitness costs without considering bacterial microenvironments in humans and other animals.
细菌耐药性和生长适应性之间的关系是一个有争议的话题，但一些抗生素耐药性突变在实验室中显然存在适应性成本。然而，这些成本是否转化为自然栖息地的有害影响尚不确定。以前，耐药性突变的适应性影响主要在营养丰富、生长迅速的条件下进行了描述，而这些条件是细菌在自然栖息地中很少遇到的。在人体的不同部位，碳、磷、铁或氧的限制是细菌病原体遇到的条件。在这里，我们测量了在利福平耐药细菌分离株中常见的四种不同 rpoB 突变的适应性。在营养过剩和四种不同营养限制状态下生长的大肠杆菌群体中，研究了这些突变和其他等位基因的适应性特性和出现。与先前的发现一致，所有四种突变在营养丰富的条件下都表现出有害的适应性效应。相比之下，我们发现营养限制条件下具有正或中性的适应性效应。两种特定的 rpoB 等位基因在磷酸盐限制下具有显著的适应性增加，并且这些等位基因在磷酸盐限制下特别高频率地出现。这些发现表明，如果不考虑人类和其他动物中的细菌微环境，就没有意义在不考虑细菌微环境的情况下得出关于适应性成本的一般性结论。
