Current Knowledge and Perspectives of Phage Therapy for Combating Refractory Wound Infections

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5465 - 5465

Published: May 17, 2024

Wound infection is one of the most important factors affecting wound healing, so its effective control critical to promote process healing. However, with increasing prevalence multi-drug-resistant (MDR) bacterial strains, prevention and treatment infections are now more challenging, imposing heavy medical financial burdens on patients. Furthermore, diminishing effectiveness conventional antimicrobials declining research new antibiotics necessitate urgent exploration alternative treatments for infections. Recently, phage therapy has been revitalized as a promising strategy address challenges posed by in era antibiotic resistance. The use treating infectious diseases demonstrated positive results. This review provides an overview mechanisms, characteristics, delivery methods combating pathogenic bacteria. Then, we focus clinical application various therapies managing refractory infections, such diabetic foot well traumatic, surgical, burn Additionally, analysis potential obstacles practice presented, along corresponding strategies addressing these issues. serves enhance our understanding innovative avenues

Language: Английский

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Engineered Bacteriophage-Based In Situ Vaccine Remodels a Tumor Microenvironment and Elicits Potent Antitumor Immunity

ACS Nano, Journal Year: 2024, Volume and Issue: 18(19), P. 12194 - 12209

Published: May 1, 2024

In situ vaccines (ISVs) utilize the localized delivery of chemotherapeutic agents or radiotherapy to stimulate release endogenous antigens from tumors, thereby eliciting systemic and persistent immune activation. Recently, a bioinspired ISV strategy has attracted tremendous attention due its features such as an adjuvant effect genetic plasticity. M13 bacteriophages are natural nanomaterials with intrinsic immunogenicity, flexibility, cost-effectiveness for large-scale production, demonstrating potential application in cancer vaccines. this study, we propose based on engineered bacteriophage targeting CD40 (M13CD40) dendritic cell (DC)-targeted stimulation, named H-GM-M13CD40. We induce immunogenic death tumor through local (S)-10-hydroxycamptothecin (HCPT), followed by intratumoral injection granulocyte-macrophage colony stimulating factor (GM-CSF) M13CD40 enhance DC recruitment demonstrate that can result significant accumulation activation DCs at site, reversing immunosuppressive microenvironment. addition, H-GM-M13CD40 synergize PD-1 blockade abscopal effects cold models. Overall, our study verifies immunogenicity provides proof concept phage function ISVs.

Language: Английский

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CRISPR-Cas in Pseudomonas aeruginosa provides transient population-level immunity against high phage exposures

The ISME Journal, Journal Year: 2024, Volume and Issue: 18(1)

Published: Jan. 1, 2024

The prokaryotic adaptive immune system, CRISPR-Cas (clustered regularly interspaced short palindromic repeats; CRISPR-associated), requires the acquisition of spacer sequences that target invading mobile genetic elements such as phages. Previous work has identified ecological variables drive evolution CRISPR-based immunity model organism Pseudomonas aeruginosa PA14 against its phage DMS3vir, resulting in rapid extinction. However, it is unclear if and how stable acquired within bacterial populations, this depends on environment. Here, we examine dynamics CRISPR loss over a 30-day experiment identify conditions tip balance between long-term maintenance versus invasion alternative resistance strategies support persistence. Specifically, find both initial dose reinfection frequencies determine whether or not maintained long term, can coexist with bacteria. At population genetics level, emergence are associated high levels diversity subsequently decline due to bacteria carrying pilus-associated mutations. Together, these results provide resolution demonstrate cumulative burden determines effectiveness ecologically relevant timeframes.

Language: Английский

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Guiding antibiotics towards their target using bacteriophage proteins

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 20, 2024

Abstract Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance efficacy of antibiotics guiding their targets, increasing local concentration at site infection. While recently described nanodelivery promising, they generally not easy adapt different lack biocompatibility or specificity. Here, created that source targeting proteins from bacteriophages. Bacteriophage receptor-binding cell-wall binding domains conjugated nanoparticles, for targeted delivery rifampicin, imipenem, ampicillin pathogens. They show excellent specificity accumulate infection deliver antibiotic payload. Moreover, suppress pathogen more effectively than 16 32-fold higher doses free This study demonstrates bacteriophage sourced promising candidates guide systems. Their specificity, availability, make great options needed combat infections.

Language: Английский

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Characterization, antibacterial, and cytotoxic activities of silver nanoparticles using the whole biofilm layer as a macromolecule in biosynthesis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 3, 2024

Abstract Recently, multi-drug resistant (MDR) bacteria are responsible for a large number of infectious diseases that can be life-threatening. Globally, new approaches targeted to solve this essential issue. This study aims discover novel antibiotic alternatives by using the whole components biofilm layer as macromolecule synthesize silver nanoparticles (AgNPs) promising agent against MDR. In particular, biosynthesized biofilm-AgNPs were characterized UV-Vis spectroscopy, electron microscopes, Energy Dispersive X-ray (EDX), zeta sizer and potential while their effect on bacterial strains normal cell lines was identified. Accordingly, have lavender-colored solution, spherical shape, with size range 20–60 nm. Notably, they inhibitory effects when used various concentrations ranging between 12.5 25 µg/mL. addition, an effective synergistic combined phage ZCSE9 inhibit kill Salmonella enterica concentration 3.1 conclusion, work presents biosynthesis preparation AgNPs antibacterial purposes reduce possible toxicity reducing MICs ZCSE9.

Language: Английский

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