Within-host adaptation is a hallmark of chronic bacterial infections, involving substantial genomic changes. Recent large-scale genomic data from prolonged infections allow the examination of adaptive strategies employed by different pathogens and open the door to investigate whether they converge toward similar strategies. Here, we compiled extensive data of whole-genome sequences of bacterial isolates belonging to miscellaneous species sampled at sequential time points during clinical infections. Analysis of these data revealed that different species share some common adaptive strategies, achieved by mutating various genes. Although the same genes were often mutated in several strains within a species, different genes related to the same pathway, structure, or function were changed in other species utilizing the same adaptive strategy (e.g., mutating flagellar genes). Strategies exploited by various bacterial species were often predicted to be driven by the host immune system, a powerful selective pressure that is not species specific. Remarkably, we find adaptive strategies identified previously within single species to be ubiquitous. Two striking examples are shifts from siderophore-based to heme-based iron scavenging (previously shown for Pseudomonas aeruginosa) and changes in glycerol-phosphate metabolism (previously shown to decrease sensitivity to antibiotics in Mycobacterium tuberculosis). Virulence factors were often adaptively affected in different species, indicating shifts from acute to chronic virulence and virulence attenuation during infection. Our study presents a global view on common within-host adaptive strategies employed by different bacterial species and provides a rich resource for further studying these processes.
Bibliographical noteFunding Information:
We are grateful to Y. Altuvia and I. Rosenshine for fruitful discussions and invaluable advice. We thank M. Barsheshet and A. Bar for their support and comments and R. Hershberg, E. Bolotin, T. Pupko, U. Gophna, A. Stern, and R. Pascale for their helpful advice and assistance. We thank Y. Yadegari for the illustration in figure 5a. This work was supported by the Israel Science Foundation, administered by the Israeli Academy for Sciences and Humanities (grant 876/17). Y.E.G. is partially supported by fellowships of the Hoffman Program, the Foulkes Foundation, and the Data Sciences program of the Planning and Budgeting Committee of the Israel Council for Higher Education.
© 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
- infectious diseases
- microbial genetics
- within-host adaptation
- within-host evolution