Enzymes in Synergy: Bacteria Specific Molecular Probe for Locoregional Imaging of Urinary Tract Infection in vivo.

Uropathogenic Escherichia coli (UPECs) is a leading cause for urinary tract infections (UTI), accounting for 70-90% of community or hospital-acquired bacterial infections owing to high recurrence, imprecision in diagnosis and management, and increasing prevalence of antibiotic resistance. Current methods for clinical UPECs detection still rely on labor-intensive urine cultures that impede rapid and accurate diagnosis for timely UTI therapeutic management. Herein, we developed a first-in-class near-infrared (NIR) UPECs fluorescent probe (NO-AH) capable of specifically targeting UPECs through its collaborative response to bacterial enzymes, enabling locoregional imaging of UTIs both in vitro and in vivo. Our NO-AH probe incorporates a dual protease activatable moiety, which first reacts with OmpT, an endopeptidase abundantly present on outer membrane of UPECs, releasing an intermediate amino acid residue conjugated with a NIR hemicyanine fluorophore. Such liberated fragment would be subsequently recognized by aminopeptidase (APN) within periplasm of UPECs, activating localized fluorescence for precise imaging of UTIs in complex living environments. The peculiar specificity and selectivity of NO-AH, facilitated by the collaborative action of bacterial enzymes, features a timely and accurate identification of UPECs-infected UTIs, which could overcome misdiagnosis in conventional urine tests, thus opening new avenues towards reliable UTI diagnosis and personalized antimicrobial therapy management.

Antimicrobial Photodynamic Therapy for the Remote Eradication of Bacteria.

The emergence of multi-drug resistant bacteria strains has been an uphill battle in modern healthcare worldwide, due to the increasing difficulty of killing them. The evolving pathogenicity of bacteria has led to researchers searching for more effective antimicrobial therapeutics to successfully eliminate them without undesirable consequences to the human body. In recent years, antimicrobial photodynamic therapy (APDT), an obsolete technique for cancer treatments, has been reported to eradicate bacteria and biofilm-related infections. The principle of antimicrobial photodynamic therapy solely relies on the photosensitizers (PSs) generating reactive oxygen species, in the presence of oxygen and light, to destroy pathogens. Thus, it can target a broad spectrum of microorganisms, owing to the indirect interaction between PSs and the bacteria, resulting in the less likelihood for the development of drug resistant bacteria strains. This review will focus on the recent progress of APDT in the last five years and some future perspectives of APDT. The mechanism of APDT against bacteria and biofilms, various PSs used for APDT, and some common multidrug-resistant bacteria strains will be briefly introduced. The reported in vivo applications of APDT in the several types of bacterial infections that includes periodontitis, wound infections, keratitis, endophthalmitis and tuberculosis in the last five years will be summarized in detail.

Tumour enzyme affinity mediated peptide molecular crowding for targeted disruption of hyperactivated glucose uptake.

An unconventional environment-responsive molecular crowding via specific binding between small molecule peptide inhibitor derivatives and an overexpressed tumour enzyme has been developed. Assemblies of such short peptides selectively localize on tumour surfaces and exhibited unique functions in disrupting hyperactivated glucose uptake, providing novel insights towards strategic tumour treatment.