Abstract
Campylobacter jejuni, a major cause of bacterial gastroenteritis, is capable of surviving in diverse hosts, including free-living amoebae such as Acanthamoeba. However, the molecular mechanisms that facilitate its intracellular persistence and subsequent transfer remain poorly defined. Here, we hypothesize that C. jejuni employs a biphasic actin-remodelling strategy, mediated by the effector proteins CiaI and CiaD, to reposition and remodel host mitochondria, promoting mitochondrial aggregation and iron homoeostasis. Using dual proteomics, microscopy, biochemical assays, and defined genetic mutants, we show that actin polymerization and CiaI are critical for mitochondrial interaction. We found that CiaI binds nucleotides with cooperative kinetics, acting as a molecular switch, and is crucial for C. jejuni localization near mitochondria, while CiaD promotes actin polymerization and acanthopodia formation to facilitate uptake. We propose a two-phase model: early actin polymerization repositions mitochondria, followed by localized actin depolymerization and mitochondrial remodelling. Iron chelation promotes bacterial survival, suggesting that oxidative stress functions as a host defence. These findings highlight a sophisticated mechanism of intracellular adaptation by C. jejuni that may be relevant to pathogenesis and identify new potential targets for disrupting its environmental and clinical persistence.
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Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD065850, and all analysed data underlying Table 1 can be found in Supplementary Data 1 and 2. All biological replicate flow cytometry data presented in this study can be found in the supplementary Information. Source values underlying all graphs presented in the study can be found in supplementary data 3.
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Acknowledgements
We thank Christian Chiu for providing training, technical assistance and analyses using flow cytometry. We thank Steven Lynham and Xiaoping Yang from the Centre of Excellence for Mass Spectrometry at King’s College London for proteomic analyses. We thank Professor Serge Mostowy for his advice. We also acknowledge the Imaging and Cytometry Platform for Infection Biology (LSHTM). This work was supported by the Biotechnology and Biological Sciences Research Council Institute Strategic Programme BB/R012504/1 constituent project BBS/E/F/000PR10349 to B.W.W.
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F.N. conceptualized, designed, performed experiments and wrote the first draft; F.N. and B. W.W. edited the final draft of the manuscript
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Nasher, F., Wren, B.W. A two-step actin-mediated strategy enables Campylobacter jejuni to promote mitochondrial aggregation and iron homeostasis, for intracellular survival and persistence. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09713-9
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DOI: https://doi.org/10.1038/s42003-026-09713-9
