Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.03.16.484526

A mathematical model of antibiotic resistance gene flow from livestock and spread amongst humans

Fryer, H.
View original source ↗Export metadata ↓

Abstract

The evolution and spread of antibiotic resistance poses a major threat to human health. The high level of antibiotic use in the rearing of livestock is contributing to the origin and persistence of antibiotic resistance amongst humans. Understanding how resistance genes spread from livestock to humans and investigating the impact of managing antibiotic use in livestock will be important for guiding strategies to reduce the risk to humans. We have developed a mathematical model of the transmission of resistance genes from livestock to humans and their spread amongst the human population. Using this framework we demonstrate that although resistant zoonotic foodborne infections do not contribute significantly to the annual burden of death, they could be a source of resistance amongst other pathogens, including those that exclusively spread between humans. Amongst these pathogens, only livestock-derived resistant strains that are associated with a net fitness cost would be expected to decline in prevalence following control strategies aimed at reducing the impact on humans of antibiotic use in livestock. Author SummaryAntibiotics are an essential component of human health care. They are also used in the rearing of livestock for human consumption, which contributes to the development of antibiotic resistant pathogens. Although humans are known to be at risk from antibiotic resistance that evolves amongst livestock, the number of human lives that are at stake remains unclear. Furthermore, the number of lives that could be saved through interventions to reduce antibiotic use in livestock has not been evaluated. Here, we have developed a mathematical framework to explore these questions. Using this framework we explicitly demonstrate that there are too many uncertainties to calculate the number of preventable human deaths. Nevertheless, the importance of reserving new and currently effective antibiotics for human use is clear. Once resistance genes that do not have a fitness disadvantage have spread from livestock to humans, it is too late for interventions targeted at livestock to affect their prevalence in humans in the long term.

Explore related subjects

zoologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Fryer, H.. 2022-03-18. A mathematical model of antibiotic resistance gene flow from livestock and spread amongst humans. https://doi.org/10.1101/2022.03.16.484526

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

KEEP EXPLORING

Related preprints

bioRxiv2026

Comparing the Influence of Habitat Configuration on Population Connectivity and Genetic Structure Using Congeneric Species Across Multiple Taxa

Abstract Habitat configuration influences population connectivity and, consequently, genetic structure. River networks provide heterogeneous, hierarchically arranged environments that shift drastically from upstream to downstream. We compared congeneric species across Ephemeroptera, Plecoptera, and Trichoptera, emphasizing longitudinal replacement (upstream to downstream) and the rarely studied wet rock (hygropetric) habitats. We surveyed six rivers on the Muroto Peninsula, Japan, qualitatively sampling aquatic insects at 63 sites. Cluster analysis based on the environmental data classified surveyed sites into four clusters. We analyzed a total of 10 species from four genera that exhibit longitudinal replacement patterns within genera. Genetic analyses based on the mitochondrial cytochrome c oxidase subunit I region revealed that upstream species showed higher genetic diversity than downstream species. In contrast, species adapted to hygropetric exhibited the lowest genetic differentiation among all habitat types. A novel contribution of this study is the inclusion of hygropetric species. The surprisingly low differentiation in hygropetric species suggests high connectivity, similar to lentic species. By comparing congeneric taxa across orders within environmentally similar rivers, we reduce phylogenetic and environmental confounds, strengthening inference that habitat configuration and dispersal traits jointly shape genetic structure. These findings provide a new perspective on riverine spatial ecology and underscore the importance of microhabitat-aware comparisons for evolutionary inference.

zoology↗
bioRxiv2026

Late lactation represents the main window for sow-to-piglet transmission of persistent gut strains

The gut microbiota plays a key role in piglet health, and maternal microbial transmission may represent a promising lever to shape early-life microbiota and prevent post-weaning digestive disorders. This study aimed to better characterize sow-to-piglet microbiota transmission and persistence using a long-read metabarcoding approach targeting the 16S-ITS-23S region. Fecal samples (n = 204) were collected from 17 families, a family being as sow and three of her piglets, at multiple stages: late gestation (G110), early (L6) and late lactation (L28) for sows; early lactation (L6), late lactation (L28), and 5 days post-weaning for piglets. To approximate strain-level resolution, a putative strain (PS) approach was developed by clustering ASVs (n = 6064) affiliated with the same species based on abundance covariance (r > 0.9), resulting in 4857 PS. Piglet microbiota progressively diversified during lactation and converged toward that of sow. In sows, 27 {+/-} 6% of PS were persistent from late gestation to late lactation. In piglets, only 4.2 {+/-} 2.5% of PS persisted from d6 to 5 days post-weaning. Persistent PS in piglets were mainly affiliated with Limosilactobacillus reuteri and Lactobacillus amylovorus followed with Holdemanella porci and H. biformis, Lentihominibacter hominis and Dorea formicigenerans. Shared PS were significantly higher within families than between unrelated pairs (p < 0.05). Maternal transmission peaked at the end of lactation (35 {+/-} 7% at L28). Persistent transmitted PS represented 2.7 {+/-} 1.6% (d6-post-weaning) and 15.4 {+/-} 5.6% (d28-post-weaning). Early-transmitted persistent PS were mainly affiliated with Limosilactobacillus reuteri, Lactobacillus amylovorus, and Paraeggerthella hominis, whereas late-transmitted persistent PS were associated with Prevotella spp., Sphaerochaeta globosa, and Bariatricus comes. These findings highlight the significance of maternal transmission in shaping the post-weaning microbiota and identify late lactation as a critical window for microbiota transfer.

zoology↗
bioRxiv2026

RISC-Bound Small RNA Sequencing Provides Insights into Guide Strand Selection and siRNA Trimming and Tailing Following Insecticidal dsRNA Delivery

RNA interference (RNAi) offers a sequence-specific approach to pest control. In insects, Dicer-2 processes double-stranded RNA (dsRNA) into small interfering RNA (siRNA) duplexes, from which the RNA-induced silencing complex (RISC) retains a guide strand. Only antisense-loaded RISC can mediate cleavage of the target transcript. However, how sequence features shape the RISC-bound siRNA pool in pests remains poorly understood, limiting opportunities for sequence optimization. Here, we profiled RISC-bound siRNAs following injection of 34 insecticidal dsRNAs targeting 11 essential genes in Tribolium castaneum larvae. We computationally reconstructed 7,879 siRNA pairs and examined associations between sequence features and strand bias. Differences in GC identity at terminal paired positions 1 to 5, used as a proxy for local thermodynamic asymmetry, correlated with strand bias, with the strongest correlations at the first two paired positions. ORF targeting and reduced predicted antisense self-folding were also associated with higher antisense fractions. Analysis of non-templated terminal additions revealed predominantly 3-prime uridylation, a known signature of small RNA turnover, along with putative 3-prime trimming. Among ORF-associated siRNA pairs, sense strands showed higher relative U-tailing abundance, based on 3-prime uridylated and putatively trimmed-and-3-prime-uridylated reads relative to perfect 21-nt reads, than antisense strands. Antisense strands with the least predicted self-folding also showed low relative U-tailing abundance. These observations are consistent with sequence-dependent contributions from both guide-strand selection and differential post-RISC-loading siRNA retention, although a causal link remains to be established. The identified associations provide a basis for testing whether dsRNA sequence optimization can improve pest control efficacy and reduce off-target activity.

zoology↗