Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.12.16.520823

A phylogenetic approach to studying the roles of within-host evolution and between-host transmission of resistance for clinical Escherichia coli infections

Van Nouhuijs, F.·Arakkal Antony, M.·Orcales, F.·Gozashti, L.·Roy, S. W.·Ogbunugafor, C. B.·Pennings, P. S.
View original source ↗Export metadata ↓

Abstract

Bacterial antibiotic resistance represents a public health concern that will remain relevant for the foreseeable future. Antibiotic resistant bacterial infections can occur in two ways: (1) a host is infected by a resistant bacterial strain (due to between-host transmission of resistance), or (2) a host is infected infection by a susceptible strain, followed by the de novo evolution or acquisition of resistance (due to within-host evolution of resistance). While both are critical to understanding how the evolution of resistance happens in natural settings, the relative rate at which they occur is unclear. Here, we employ phylogenetic comparative methods to examine the evolutionary dynamics of resistance in Escherichia coli for multiple common antibiotics. We report evolutionary patterns consistent with common de novo evolution of resistance for some antibiotics and sustained transmission of resistant strains for others. For example, we observe 79 putative de novo resistance evolution events for resistance to Cefuroxime but only 31 for resistance to Ciprofloxacin, despite similar numbers of observed infections (239 and 267 respectively). We find that clusters of resistance are generally larger for Ciprofloxacin, Ceftazidima and AmoxiClav, which suggests that for these drugs, resistance is often transmitted from patient to patient. In contrast, we find that cluster sizes for resistance are generally smaller for PipTaz, Cefuroxime and Gentamicin, suggesting that resistance to these drugs is less often transmitted from patient to patient and instead evolves de novo. In addition to differences between drugs, we also find that cluster sizes were generally larger in phylogroup B2 compared to the other phylogroups, suggesting that transmission of resistant strains is more common in this phylogroup compared to the others. Our study proposes new approaches for determining the importance of de novo evolution or acquisition (within-host evolution) from resistance from infection with an already resistant strain (between-host transmission). Significantly, this work also bridges an important gap between evolutionary genomics and epidemiology, opening up a range of opportunities for studying the evolutionary dynamics of bacterial antibiotic resistance.

Explore related subjects

evolutionary biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Van Nouhuijs, F., Arakkal Antony, M., Orcales, F., Gozashti, L., Roy, S. W., Ogbunugafor, C. B., Pennings, P. S.. 2022-12-19. A phylogenetic approach to studying the roles of within-host evolution and between-host transmission of resistance for clinical Escherichia coli infections. https://doi.org/10.1101/2022.12.16.520823

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

RELAX does not reproduce its own estimates at default settings, and its output does not show it

Selection-intensity estimates from RELAX are reported as a point value of K with a likelihood-ratio P. We report that, at default settings and on data of ordinary size, the program does not reproduce its own fits. Of 27 enzyme entries refitted under two optimiser configurations, none reproduced its log-likelihood to within 0.01 units; the median change was 103 units, the largest over 3,400, and four verdicts reversed. Eighty null orthologues reproduced none. A byte-identical command returned a distinct likelihood on every repetition, single-threaded, across three releases, and on alignments simulated under the fitted model, where 3.3 per cent of replicates reproduced. The documented random-number seed never reaches the generator when assigned on the command line, yet reads back as the value supplied. PAML localises the cause: its two-ratio model, without site classes, reproduced its log-likelihood for all 288 genes; its site-class models agreed for 27 to 67 per cent. The instability follows the mixture over sites, not the program. The output does not show it: 46 of 410 fits ended with a negative likelihood-ratio statistic, impossible under convergence, and 123 of 410 report a K re-estimated under a domain restriction rather than the unconstrained maximum. Of 234 published studies using RELAX, none reported a seed. Seeding while holding the thread count at one reproduced sixty of sixty runs on twenty genes under two releases; the seed alone reproduced none of five, and no documentation states the second condition. We recommend that fits be repeated and their dispersion published.

evolutionary biology↗
bioRxiv2026

Sequential accumulation of adaptive alleles forms an inversion supergene in deer mice

Supergenes are clusters of co-inherited loci that affect multiple or complex phenotypes. Despite the growing number of chromosomal inversions identified as supergenes in natural populations, their molecular basis and evolutionary history often remain obscure. Here, we identified two candidate genes, Slc45a2 and Npr3, within a 41-Mb inversion supergene in the deer mouse (Peromyscus maniculatus) that respectively drive darker coats and longer tails - two traits associated with forest adaptation. Mice homozygous for the inversion (inv/inv) exhibit elevated Slc45a2 expression in melanocytes relative to the congenic standard genotype (std/std), disrupting pheomelanin production. In parallel, downregulation of Npr3 in inv/inv mouse growth plates prolongs postnatal growth of caudal vertebrae, resulting in tail elongation. Population-level analyses further implicate that this supergene arose through the subsequent accumulation of the Npr3 allele within the inversion, rather than by capturing all beneficial mutations at its origin.

evolutionary biology↗
bioRxiv2026

Toxin structure shapes palatability in a chemically defended butterfly

The toxicity of chemical defences is well studied, but the potential contribution of compound structure to predator deterrence remains largely unexplored. Whether predation acts more strongly on toxicity or unpalatability remains largely untested, partly because few systems allow toxin structure to vary independently of quantity. Heliconius sara larvae provide such a system: those reared on Passiflora auriculata sequester cyclopentenyl cyanogenic glucosides (CGs), while those reared on P. biflora biosynthesise comparable quantities of aliphatic CGs. Using two invertebrate predators, Camponotus floridanus ants and Hierodula membranacea mantids, we tested whether this structural difference affects palatability independent of toxicity. Mantids rejected larvae with cyclopentenyl CGs more often than larvae with aliphatic CGs, despite no detectable difference in total CG content. This pattern was mirrored in extract-based assays with ants, independently of cyanide release: extracts with cyclopentenyl CGs remained deterrent, while extracts with aliphatic CGs did not differ in deterrence from water. Live larvae, by contrast, elicited similar responses from ants regardless of CG structure. These results show that variation in toxin structure can strongly affect palatability, with some compounds conferring greater protection than others. This demonstrates the importance of chemical structural diversity in the evolution of chemical defences.

evolutionary biology↗