Exceptions to the rule: Why does resistance evolution not undermine antibiotic therapy in all bacterial infections?

Bhattacharya, Amrita; Aluquin, Anton; Kennedy, David

doi:10.1101/2021.12.15.472803

Cited by 1 publication

(1 citation statement)

References 54 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While our results support the importance of AMR in the success of ST131, they raise other questions about the nature of AMR’s benefit. Rather than bolstering the fitness of a lineage purely by conferring antibiotic resistance, the benefit of these genes may not be entirely dependent on the presence of antibiotics [70]. This will be an important distinction to untangle moving forward.…”

Section: Discussionmentioning

confidence: 99%

Quantifying the genomic determinants of fitness inE. coliST131 using phylodynamics

Kepler,

Jara,

Mahmud

et al. 2024

Preprint

View full text Add to dashboard Cite

Antimicrobial resistant pathogens such asEscherichia colisequence type 131 (ST131) pose a serious threat to public health globally. In the United States, ST131 acquired multiple antimicrobial resistance (AMR) genes and rapidly grew to its current high prevalence in healthcare settings. Notably, this coincided with the introduction and widespread use of antibiotics such as fluoroquinolones, suggesting AMR as the major driver of ST131’s expansion. Yet, within ST131, there remains considerable diversity between strains in resistance profiles and their repertoires of virulence factors, stress factors, plasmids, and other accessory elements. Understanding which genomic features contribute to ST131’s competitive advantage and their relative effects on population-level fitness therefore poses a considerable challenge. Here we use phylodynamic birth-death models to estimate the relative fitness of different ST131 lineages from bacterial phylogenies. By extending these phylodynamic methods to allow multiple genomic features to shape bacterial fitness, we further quantify the relative contribution of individual AMR genes to ST131’s fitness. Our analysis indicates that while many genomic elements, including various AMR genes, virulence factors, and plasmids, have all contributed substantially to ST131’s rapid growth, major increases in ST131’s fitness are largely attributable to mutations in gyrase A that confer resistance to fluoroquinolones.Author summaryST131 is a pandemic lineage ofE. colithat has spread globally and is now responsible for a large percentage of blood and urinary tract infections that cannot be treated with many common antibiotics. While antibiotic resistance has undoubtedly given ST131 a competitive edge, the relative importance of resistance compared with other factors shaping a pathogen’s growth or transmission potential (i.e. fitness) is often difficult to measure in natural settings. Here, we present a method that allows us to look at the entire spectrum of factors determining a pathogen’s fitness and estimate the individual contribution of each component to pathogen’s overall fitness. Our results suggest that resistance to fluoroquinolones, a widely used class of antibiotics, provides ST131 with a disproportionately large fitness advantage relative to many other factors with more moderate fitness effects. Understanding what determines the fitness of ST131 therefore provides insights that can be used to curb the spread of resistance and monitor for emerging lineages with high pandemic potential due to shared fitness enhancing attributes.

show abstract

Section: Discussionmentioning

confidence: 99%