Phototrophic purple bacteria as optoacoustic in vivo reporters of macrophage activity

Abstract

Τhe morphology, physiology and immunology, of solid tumors exhibit spatial heterogeneity which complicates our understanding of cancer progression and therapy response. Understanding spatial heterogeneity necessitates high resolution in vivo imaging of anatomical and pathophysiological tumor information. We introduce Rhodobacter as bacterial reporter for multispectral optoacoustic (photoacoustic) tomography (MSOT). We show that endogenous bacteriochlorophyll a in Rhodobacter gives rise to strong optoacoustic signals >800 nm away from interfering endogenous absorbers. Importantly, our results suggest that changes in the spectral signature of Rhodobacter which depend on macrophage activity inside the tumor can be used to reveal heterogeneity of the tumor microenvironment. Employing non-invasive high resolution MSOT in longitudinal studies we show spatiotemporal changes of Rhodobacter spectral profiles in mice bearing 4T1 and CT26.WT tumor models. Accessibility of Rhodobacter to genetic modification and thus to sensory and therapeutic functions suggests potential for a theranostic platform organism.

Engineered Rhodobacter capsulatus as a Phototrophic Platform Organism for the Synthesis of Plant Sesquiterpenoids

“…Since R. capsulatus was identified as a plant growth promoting bacterium naturally occurring in root microbiomes of various plants including Brassica rapa , rice, sugar beet, and barley (Çakmakçi et al, 2006, 2007; Gamal-Eldin and Elbanna, 2011; Hussein et al, 2014), appropriately engineered Rhodobacter strains delivering selected terpenes may constitute a possible future means for plant protection and reduction of fertilizer application in agricultural crop production. (ii) In addition, we could recently demonstrate that R. capsulatus can be used as an in vivo marker for multispectral optoacoustic tomography-based analysis of macrophage presence and activity inside of solid tumors (Peters et al, 2019). Therefore, production and reporter properties of R. capsulatus could also be combined to develop a new theranostic platform allowing selective in situ delivery of anti-cancer terpenoids together with visualization of the drug release process.…”

Challenging a Preconception: Optoacoustic Spectrum Differs from the Optical Absorption Spectrum of Proteins and Dyes for Molecular Imaging

“…The sensitivity of some natural chromophores and organic dyes to aggregation and other environmental changes has been exploited for various sensing applications in OA imaging (Jiang and Pu, 2017;Lovell et al, 2011;Morgounova et al, 2013;Peters et al, 2019;. However, the photophysics underlying the changes in the OA signals of these chromophores have never been thoroughly understood or described, precluding efficient and rational exploitation of such effects for the design of next-generation functional OA labels.…”

Maltotriose-based probes for fluorescence and photoacoustic imaging of bacterial infections

“…A few other examples rely on genetically encoding bacteria with reporters, such as photo-switchable chromoproteins 26,27 and violacein 28 , have been reported. While these strategies allow non-invasive imaging of bacteria in vivo using PAI, the application of such platform would be limited to visualizing biochemistry, pathophysiological processes, and gene expression profiles in living subjects as well as imaging tumor homing bacteria 29 and cannot be used for diagnosing bacterial infections.…”