Abstract
There is growing interest in genetically expressed reporters for in vivo studies of bacterial colonization in the context of infectious disease research, studies of the bacterial microbiome or cancer imaging and treatment. To empower non-invasive high-resolution bacterial tracking with deep tissue penetration, we herein use the genetically controlled biosynthesis of the deep-purple pigment Violacein as a photobleaching-resistant chromophore label for in vivo optoacoustic (photoacoustic) imaging in the near-infrared range. We demonstrate that Violacein-producing bacteria can be imaged with high contrast-to-noise in strongly vascularized xenografted murine tumors and further observe that Violacein shows anti-tumoral activity. Our experiments thus identify Violacein as a robust bacterial label for non-invasive optoacoustic imaging with high potential for basic research and future theranostic applications in bacterial tumor targeting.
Highlights
IntroductionRobust detection of genetically labeled bacteria in vivo via optoacoustic imaging has so far not been accomplished
Vio is enzymatically generated from the sole precursor tryptophan by five enzymes (VioA-E) that have originally been cloned from Chromobacterium violaceum[18]
In search for a potent bacterial label that affords high-resolution, three dimensional bacterial imaging in tissues, we characterized the photophysical and biochemical properties of Vio with respect to optoacoustic detection and interrogated its performance as a bacterial label for optoacoustic imaging compared to melanin or fluorescent proteins
Summary
Robust detection of genetically labeled bacteria in vivo via optoacoustic imaging has so far not been accomplished. One reason for this may be that common fluorescent proteins or chromoproteins often exhibit poor photostability making it challenging to obtain robust signals in optoacoustic imaging applications[13]. Enzymatically generated biosynthetic pigments such as melanin have the advantage of signal amplification because each genetically expressed enzyme can turn over many substrates per unit time. In search for a potent bacterial label that affords high-resolution, three dimensional bacterial imaging in tissues, we characterized the photophysical and biochemical properties of Vio with respect to optoacoustic detection and interrogated its performance as a bacterial label for optoacoustic imaging compared to melanin or fluorescent proteins. We further performed in vivo studies to characterize the capacity to detect Vio-labeled bacteria by multispectral optoacoustic tomography (MSOT) in tumor-bearing mice
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