Bacterial evolution during human infection: Adapt and live or adapt and die

Abstract

Microbes are constantly evolving. Laboratory studies of bacterial evolution increase our understanding of evolutionary dynamics, identify adaptive changes, and answer important questions that impact human health. During bacterial infections in humans, however, the evolutionary parameters acting on infecting populations are likely to be much more complex than those that can be tested in the laboratory. Nonetheless, human infections can be thought of as naturally occurring in vivo bacterial evolution experiments, which can teach us about antibiotic resistance, pathogenesis, and transmission. Here, we review recent advances in the study of within-host bacterial evolution during human infection and discuss practical considerations for conducting such studies. We focus on 2 possible outcomes for de novo adaptive mutations, which we have termed “adapt-and-live” and “adapt-and-die.” In the adapt-and-live scenario, a mutation is long lived, enabling its transmission on to other individuals, or the establishment of chronic infection. In the adapt-and-die scenario, a mutation is rapidly extinguished, either because it carries a substantial fitness cost, it arises within tissues that block transmission to new hosts, it is outcompeted by more fit clones, or the infection resolves. Adapt-and-die mutations can provide rich information about selection pressures in vivo, yet they can easily elude detection because they are short lived, may be more difficult to sample, or could be maladaptive in the long term. Understanding how bacteria adapt under each of these scenarios can reveal new insights about the basic biology of pathogenic microbes and could aid in the design of new translational approaches to combat bacterial infections.

A statistical genomics framework to trace bacterial genomic predictors of clinical outcomes in Staphylococcus aureus bacteraemia

“…However, it is unclear whether clinical outcomes of bacterial infections are dependent on bacterial genotypes, as shown by bacterial GWAS of clinical outcomes, that have been either negative or have not been reproduced across independent cohorts. Bacterial adaptation can be frequently detected in clinical infections (Culyba and Van Tyne 2021), leading to antibiotic resistance, antibiotic tolerance, or immune evasion, and thus potentially driving treatment failure (Balaban, Helaine et al 2019). Here, we propose a statistical genomics framework that incorporates convergent evolution explicitly and tracks molecular signatures of adaptation across three independent SAB patient cohorts to build a model of bacterial genotype-phenotype associations for treatment outcomes.…”

Convergent Evolution of Antibiotic Tolerance in Patients with Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia

“…Therefore, we suspect prior studies of PB did not have the sampling depth to detect these minor subpopulations. Future studies of PB may achieve even greater sensitivity by sequencing the entire population of bacteria captured in blood cultures, as opposed to sequencing only a single isolate from each culture ( 14 ).…”

“… S. aureus PB can be considered a natural experiment in microbial evolution. The infecting population is large enough to contain significant genetic diversity due to spontaneous mutation and is also subject to strong selection within the host environment ( 14 ). Within-host evolution can be tracked by analyzing serial culture-positive blood samples with whole-genome sequencing (WGS).…”

Biodegradable MoOx@MB incorporated hydrogel as light-activated dressing for rapid and safe bacteria eradication and wound healing

“…Although antibiotics have been used to combat bacterial infections, the abuse/overuse of antibiotics has brought about the serious generation of drug-resistant bacteria. [1][2][3] Consequently, it is imperative to develop safe, highly effective and non-antibiotic therapeutic strategies. Nanomaterials have been investigated as therapeutic agents, relying on surface modication with biocompatible moieties.…”