Biology subjects

PENG, H.

Publications and source records attributed to PENG, H..

2 recordsLinked to original sources

bioRxiv2022

A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging

The ability to noninvasively detect bacteria at any depth inside opaque tissues has important applications ranging from infection diagnostics to tracking therapeutic microbes in their mammalian host. Current examples of probes for detecting bacteria with strain-type specificity are largely based on optical dyes, which cannot be used to examine bacteria in deep tissues due to the physical limitation of light scattering. Here, we describe a new biomolecular probe for visualizing bacteria in a cell-type specific fashion using magnetic resonance imaging (MRI). The probe is based on a peptide that selectively binds manganese and is attached in high numbers to the capsid of filamentous phage. By genetically engineering phage particles to display this peptide, we are able to bring manganese ions to specific bacterial cells targeted by the phage, thereby producing MRI contrast. We show that this approach allows MRI-based detection of targeted E. coli strains while discriminating against non-target bacteria as well as mammalian cells. By engineering the phage coat to display a protein that targets cell surface receptors in V. cholerae, we further show that this approach can be applied to image other bacterial targets with MRI. Finally, as a preliminary example of in vivo applicability, we demonstrate MR imaging of phage-labeled V. cholerae cells implanted subcutaneously in mice. The nanomaterial developed here thus represents a path towards noninvasive detection and tracking of bacteria by combining the programmability of phage architecture with the ability to produce three- dimensional images of biological structures at any arbitrary depth with MRI.

bioengineering↗

bioRxiv2022

Treatment of wound infections in a mouse model using Zn2+-releasing phage bound to gold nanorods

Infections caused by drug-resistant bacteria, particularly gram-negative organisms, are increasingly difficult to treat using antibiotics. A potential alternative is phage therapy, in which phages infect and lyse the bacterial host. However, phage therapy poses serious drawbacks and safety concerns, such as the risk of genetic transduction of antibiotic resistance genes, inconsistent pharmacokinetics, and unknown evolutionary potential. In contrast, metallic nanoparticles possess precise, tunable properties, including efficient conversion of electronic excitation into heat. In this work, we demonstrate that engineered phage-nanomaterial conjugates that target the gram-negative pathogen P. aeruginosa, are highly effective as a treatment of infected wounds in mice. Photothermal heating, performed as a single treatment (15 min) or as two treatments on consecutive days, rapidly reduced the bacterial load and released Zn2+ to promote wound healing. The phage-nanomaterial treatment was significantly more effective than systemic fluoroquinolone antibiotics in reducing both bacterial load and wound size, and was notably effective against a P. aeruginosa strain resistant to polymyxins, a last-line antibiotic therapy. Unlike these antibiotics, the phage-nanomaterial showed no detectable toxicity or systemic effects in mice, consistent with the short duration and localized nature of phage- nanomaterial treatment. Our results demonstrate that phage therapy controlled by inorganic nanomaterials can be a safe and effective antimicrobial strategy in vivo.

bioengineering↗