Dissecting organoid-bacteria interaction highlights decreased contractile force as a key factor for heart infection

Wang, A.; wang, j.; zhang, z.; yang, c.; deng, c.; Chen, G.; Li, C.; wang, q.; Dong, L.; Wang, C.

doi:10.1101/2025.04.08.647814

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bioRxiv · 10.1101/2025.04.08.647814

Dissecting organoid-bacteria interaction highlights decreased contractile force as a key factor for heart infection

Wang, A.·wang, j.·zhang, z.·yang, c.·deng, c.·Chen, G.·Li, C.·wang, q.·Dong, L.·Wang, C.

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Abstract

Bacterial endocarditis is a fatal cardiovascular disease exacerbated by weakened heart contraction, yet the direct impact of cardiac contractility on bacterial adhesion remains elusive. Here, we present a novel quantitative physics model integrating finite element analysis and live-cell imaging to uncover their strong correlation. Using this model, we quantified the real-time force magnitude generated by organoid-type cardiac microtissue derived from healthy donors and dilated cardiomyopathy patients - mimicking normal and suppressed heart contractility, respectively - to the approaching bacteria in a real fluidic system. The data revealed that weakened cardiac contractility facilitated bacterial invasion of the myocardium. Verifying this finding in a mouse transverse aortic constriction model demonstrated that increasing heart contraction efficiently mitigated bacterial invasion, with a 25% increase in heart contractility reducing endocarditis risk by 80%. Our findings demonstrate that patient-derived cardiac organoids provide a physiologically relevant platform for studying bacterial infections in vitro, offering high clinical fidelity. This platform establishes a valuable tool for drug screening and the development of novel therapeutic strategies.

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Wang, A., wang, j., zhang, z., yang, c., deng, c., Chen, G., Li, C., wang, q., Dong, L., Wang, C.. 2025-04-14. Dissecting organoid-bacteria interaction highlights decreased contractile force as a key factor for heart infection. https://doi.org/10.1101/2025.04.08.647814

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