2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
July 3rd, 2025
Version: 2
University of Exeter College of Life and Environmental Sciences
evolutionary biology
biorxiv

Antagonism between bacteriophages and macrophages decreases efficacy of a phage cocktail and increases bacteriophage resistance

Castledine, M.Open in Google Scholar•Szczutkowska, Z.Open in Google Scholar•Matthews, A.Open in Google Scholar•Walsh, S. K.Open in Google Scholar•Lewis, R.Open in Google Scholar•Kay, S.Open in Google Scholar•Willment, J. A.Open in Google Scholar•Brown, G. D.Open in Google Scholar•Buckling, A.Open in Google Scholar

Phage therapy, the use of viruses that infect bacteria (bacteriophages), is a promising complement to antibiotics during the antimicrobial resistance crisis, but treatment success is very variable. Evolution of bacterial resistance to bacteriophages and bacteriophage counter-resistance (coevolution) during therapy may explain some of this variation, the dynamics of which may be affected by interactions with the patients immune system. Here, we examine how a pathogenic bacterium, Pseudomonas aeruginosa coevolves with two clinically relevant bacteriophages (14-1 and PNM) when in the presence of macrophages (RAW 264.7 cell line). We show macrophages reduced the rate by which bacteria were killed by bacteriophages, likely by reducing bacteria-bacteriophage contact rates. Over evolutionary time-scales, macrophages increased the proportion of bacteriophage resistant bacteria compared to where macrophages were absent. These differences in resistance rates were likely driven by the early advantage in density offered by macrophages to bacteria, and exclusion of PNM from the bacteriophage cocktail which otherwise increased in frequency in the absence of macrophages. Consequently, macrophages significantly altered the short- and long-term efficacy of a bacteriophage cocktail. In line with a growing body of work, our results suggest that the patients immune system can reduce the efficacy of phage therapy, potentially driving variable outcomes in therapy success in patients.

Similar Papers

biorxiv
Thu Jul 03 2025
Hybridization load introduced by Alpine ibex hybrid swarms
Species restoration efforts can be threatened by the accumulation of deleterious mutations and inbreeding depression associated with the historic population contraction. However, even successfully restored species could face deleterious mutation swamping from hybridization with an abundant and closely related species. Here, we analyze this risk for Alpine ibex (Capra ibex), a flagship species of l...
Cilingir, F. G.
•
Landuzzi, F.
•
Brambilla, A.
•
Charrance, D.
...•
Grossen, C.
biorxiv
Thu Jul 03 2025
Sex-biased gene expression under sexually antagonistic and sex-limited selection
Sex differences in gene expression are ubiquitous, evolve quickly, and are expected to underlie phenotypic sexual dimorphism. Despite long-standing interest, the impact of sex-specific selection on the transcriptome remains poorly understood. Here, we test fundamental questions on the role of constraints on gene expression evolution arising from the mode of selection and genetic architecture. We a...
Wiberg, R. A. W.
•
Zwoinska, M. K.
•
Kaufman, P.
•
Howie, J.
•
Immonen, E.
biorxiv
Thu Jul 03 2025
Symbiotic entrenchment through ecological Catch-22
Symbiotic organisms frequently evolve obligate dependencies on hosts, but the evolutionary changes that entrench such lifestyles are poorly understood. Ant societies are vulnerable to parasitic \"myrmecophiles\": impostor species that infiltrate colonies and are often unable to survive outside of them. Here we show that obligate dependence of a myrmecophile on its host arises from irreversibility ...
Naragon, T. H.
•
Viliunas, J. W.
•
Yousefelahiyeh, M.
•
Bruckner, A.
...•
Parker, J.
biorxiv
Wed Jul 02 2025
Synergizing Bayesian and Heuristic Approaches: D-BPP Uncovers Ghost Introgression in Panthera and Thuja
Hybridization involving extinct or unsampled ("ghost") lineages profoundly influences species' evolutionary histories, but detecting such introgression remains methodologically challenging. We introduce D-BPP, a novel framework that integrates the heuristic D-statistic (or ABBA-BABA test) with Bayesian phylogenomic inference (implemented in BPP) to efficiently infer phylogenetic networks. In D-BPP...
Yang, Y.
•
Pang, X.-X.
•
Ding, Y.-M.
•
Zhang, B.-W.
...•
Zhang, D.-Y.
biorxiv
Wed Jul 02 2025
Energetic shifts reflect survival likelihood in Anopheles gambiae
Life history theory predicts that resource allocation adapts to ecological and evolutionary pressures. We investigated resource and energy in the malaria vector Anopheles gambiae following exposure to two stressors: blood meals and infection by the microsporidian Vavraia culicis. Our findings reveal the costs of blood feeding and parasitism on longevity, highlighting trade-offs in lifetime protein...
Zeferino, T. G.
•
Silva, L. M.
•
Koella, J. C.
biorxiv
Wed Jul 02 2025
Cost of altered translation accuracy shapes adaptation to antibiotics in E. coli
Protein synthesis, while central to cellular function, is error-prone. The resulting mistranslation is generally costly, but we do not know how these costs compare or interact with the costs imposed by external selection pressures such as antibiotics. We also do not know whether and how these costs are compensated during evolution. It is important to answer these questions, since mistranslation is...
Samhita, L.
•
Tamhankar, S.
•
Miranda, J.
•
Basu, A. K.
•
Agashe, D.
biorxiv
Wed Jul 02 2025
Microbiome evolution plays a secondary role in host rapid adaptation
Understanding how populations adapt to environmental change is a central goal in evolutionary biology. Microbiomes have been proposed as a source of heritable variation that is central to rapid adaptation in hosts, yet empirical evidence supporting this remains limited, particularly in naturalistic settings. We combined a field evolution experiment in Drosophila melanogaster exposed to an insectic...
Shahmohamadloo, R. S.
•
Gabidulin, A. R.
•
Andrews, E. R.
•
Rudman, S. M.
biorxiv
Wed Jul 02 2025
Avian germline-restricted chromosomes are reservoirs for active long-terminal-repeat retroviruses
Germline-restricted chromosomes (GRCs) are unique to germ cells and absent from somatic cells in songbirds. However, their contents, functions, and evolutionary mechanisms remain unclear. We performed comparative genomics on long-read assembled GRCs from male House Finch (Haemorhous mexicanus), Common Rosefinch (Carpodacus erythrinus), and Blue Tit (Cyanistes caeruleus), the first two of which are...
Fang, B.
•
Edwards, S. V.
biorxiv
Wed Jul 02 2025
Weak genetic draft and the Lewontin's paradox
Neutral theory assumes that in a population of size N, diversity results from an equilibrium between new mutations arising at rate and genetic drift that purge them at rate 1/N, predicting an equilibrium value proportional to N. The difference between this expectation and the much lower observed molecular diversity is known as Lewontin's paradox of variation. Here, we investigate the effect of ge...
Achaz, G.
•
Schertzer, E.