Dataset Information

Photocatalytic Quantum Dot-Armed Bacteriophage for Combating Drug-Resistant Bacterial Infection.

ABSTRACT: Multidrug-resistant (MDR) bacterial infection is one of the greatest challenges to public health, a crisis demanding the next generation of highly effective antibacterial agents to specifically target MDR bacteria. Herein, a novel photocatalytic quantum dot (QD)-armed bacteriophage (QD@Phage) is reported for combating green fluorescent protein-expressing Pseudomonas aeruginosa (GFP-P. aeruginosa) infection. The proposed QD@Phage nanosystem not only specifically binds to the host GFP-P. aeruginosa while preserving the infectivity of the phage itself, but also shows a superior capacity for synergistic bacterial killing by phage and by the photocatalytic localized reactive oxygen species (ROS) generated from anchored QD components. Notably, this highly targeted QD@Phage nanosystem achieves robust in vitro antibacterial elimination for both planktonic (over 99.9%) and biofilm (over 99%) modes of growth. In a mouse wound infection model, this system also shows remarkable activity in eliminating the wound infection and promoting its recovery. These results demonstrate that the novel QD@Phage nanosystem can diversify the existing pool of antibacterial agents and inspire the development of promising therapeutic strategies against MDR bacterial infection.

SUBMITTER: Wang L

PROVIDER: S-EPMC9189633 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Photocatalytic Quantum Dot-Armed Bacteriophage for Combating Drug-Resistant Bacterial Infection.

Wang Lei L Fan Xin X Gonzalez Moreno Mercedes M Tkhilaishvili Tamta T Du Weijie W Zhang Xianlong X Nie Chuanxiong C Trampuz Andrej A Haag Rainer R

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20220418 17

Multidrug-resistant (MDR) bacterial infection is one of the greatest challenges to public health, a crisis demanding the next generation of highly effective antibacterial agents to specifically target MDR bacteria. Herein, a novel photocatalytic quantum dot (QD)-armed bacteriophage (QD@Phage) is reported for combating green fluorescent protein-expressing Pseudomonas aeruginosa (GFP-P. aeruginosa) infection. The proposed QD@Phage nanosystem not only specifically binds to the host GFP-P. aeruginos ...[more]

PMID: 35434949

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Project description:BACKGROUNDSeveral molecular imaging strategies can identify bacterial infections in humans. PET affords the potential for sensitive infection detection deep within the body. Among PET-based approaches, antibiotic-based radiotracers, which often target key bacterial-specific enzymes, have considerable promise. One question for antibiotic radiotracers is whether antimicrobial resistance (AMR) reduces specific accumulation within bacteria, diminishing the predictive value of the diagnostic test.METHODSUsing a PET radiotracer based on the antibiotic trimethoprim (TMP), [11C]-TMP, we performed in vitro uptake studies in susceptible and drug-resistant bacterial strains and whole-genome sequencing (WGS) in selected strains to identify TMP resistance mechanisms. Next, we queried the NCBI database of annotated bacterial genomes for WT and resistant dihydrofolate reductase (DHFR) genes. Finally, we initiated a first-in-human protocol of [11C]-TMP in patients infected with both TMP-sensitive and TMP-resistant organisms to demonstrate the clinical feasibility of the tool.RESULTSWe observed robust [11C]-TMP uptake in our panel of TMP-sensitive and -resistant bacteria, noting relatively variable and decreased uptake in a few strains of P. aeruginosa and E. coli. WGS showed that the vast majority of clinically relevant bacteria harbor a WT copy of DHFR, targetable by [11C]-TMP, and that despite the AMR, these strains should be "imageable." Clinical imaging of patients with [11C]-TMP demonstrated focal radiotracer uptake in areas of infectious lesions.CONCLUSIONThis work highlights an approach to imaging bacterial infection in patients, which could affect our understanding of bacterial pathogenesis as well as our ability to better diagnose infections and monitor response to therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT03424525.FUNDINGInstitute for Translational Medicine and Therapeutics, Burroughs Wellcome Fund, NIH Office of the Director Early Independence Award (DP5-OD26386), and University of Pennsylvania NIH T32 Radiology Research Training Grant (5T32EB004311-12).

Project description:BackgroundExtensively drug-resistant Gram-negative bacterial (XDR-GNB) bloodstream infection (BSI) is difficult to treat and is associated with a high mortality rate in patients with hematological diseases. The aim of this study is to investigate the predisposing risk factors and the efficacy of the antibiotic treatment in these patients, including exploration of efficacy and adverse effects of high-dose tigecycline.MethodsBetween January 2013 and December 2017, 27 XDR-GNB BSI patients with hematological diseases were diagnosed and retrospectively reviewed in the current study.ResultsClinical response in patients with severe complications (such as severe neutropenia >10 days, grade III-IV acute graft-versus-host disease (aGVHD), and concurrent pneumonia) was significantly lower than in patients without or with only mild complications (P=0.033). The efficacy rate was 62.5% (10/16) in patients with tigecycline-based combination therapy regimen, 77.8% (7/9) with a high-dose tigecycline regimen, and 42.9% (3/7) with a standard-dose tigecycline regimen (P=0.36). The 30-day survival rates of patients undergoing high-dose or standard-dose tigecycline treatment were 66.7% (95% CI: 28.2-87.8) and 57.1% (95% CI: 17.2-83.7), respectively, (P=0.603). Patients with mild complications were associated with superior 30-day survival rates than patients with severe complications (93.8% vs 36.4%, P=0.001), >10 days of neutropenia (90.9% vs 33.3%, P=0.012), severe aGVHD (100% vs 40%, P=0.049), and concurrent pneumonia (84.6% vs 57.1%, P=0.048).ConclusionOur study indicated that XDR-GNB BSI in patients of hematological diseases with severe complications, such as long duration of neutropenia (>10 days) and severe aGVHD were associated with poor clinical response and short survival. We first indicated that these patients undergoing high-dose tigecycline treatment had an improved clinical response and an increased 30-day survival rate compared with the standard-dose group, although the differences were not statistically significant. This might be due to more severe complicated patients enrolled in high-dose group and the limited number size in our study.

Dataset Information

Photocatalytic Quantum Dot-Armed Bacteriophage for Combating Drug-Resistant Bacterial Infection.

Publications

Photocatalytic Quantum Dot-Armed Bacteriophage for Combating Drug-Resistant Bacterial Infection.

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