phytochlorin and Escherichia-coli-Infections

In recent years, with the emergence of various kinds of drug-resistant bacteria, existing antibiotics have become inefficient in killing these bacteria, and the formation of biofilms has further weakened the therapeutic effect. More problematically, the massive use and abuse of antibiotics have caused severe side effects. Thus, the development of ultra-efficient and safe antibacterial systems is urgently needed. Herein, a photodynamic therapy (PDT)-driven CO-controlled delivery system (Ce6&CO@FADP) is developed for synergistic antibacterial and ablation biofilms. Ce6&CO@FADP is constructed using a fluorinated amphiphilic dendritic peptide (FADP) and physically loaded with Ce6 and CORM-401. After efficiently entering the bacteria, Ce6&CO@FADP can rapidly release CO intracellularly by the massive consumption of the H

Topics: Animals; Anti-Bacterial Agents; Biofilms; Carbon Monoxide; Chlorophyllides; Dendrimers; Escherichia coli; Escherichia coli Infections; Hydrogen Peroxide; Mice; N-substituted Glycines; Peptides; Photochemotherapy; Photosensitizing Agents; Porphyrins; Singlet Oxygen; Staphylococcus aureus

The increasing occurrence of multi-antibiotic resistant microbes has led to the search for alternative methods of killing pathogens and treating infections. Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill mammalian and microbial cells. Although the photodynamic inactivation of bacteria has been known for over a hundred years, its use to treat infections has not been much developed. This may be partly due to the difficulty of monitoring the effectiveness of PDT in animal models of infection. In order to facilitate this monitoring process, we have developed a procedure that uses bioluminescent genetically engineered bacteria and a light sensitive imaging system to allow real-time visualization of infections. When these bacteria are treated with PDT in vitro, the loss of luminescence parallels the loss of colony-forming ability. We have developed several models of infections in wounds and soft-tissue abscesses in mice that can be followed by bioluminescence imaging. The size and intensity of the infection can be sequentially monitored in a non-invasive fashion in individual mice in real-time. When photosensitizers are introduced into the infected tissue followed by illumination with red light, a light-dose dependent loss of luminescence is seen. If the bacterium is invasive, the loss of luminescence correlates with increased survival of the mice, whilst animals in control groups die of sepsis within five days. Healing of the PDT treated wounds is not impaired and may actually be improved. This approach can allow many animal models of localized infections to be accurately monitored for efficacy of treatment by PDT.

Topics: Animals; Chlorophyllides; Escherichia coli Infections; Luciferases; Luminescent Measurements; Mice; Photochemotherapy; Polylysine; Porphyrins; Pseudomonas Infections; Soft Tissue Infections; Staphylococcal Infections; Transformation, Genetic; Wound Infection

The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. In this study we report on the first use of a photochemical approach to destroy bacteria infecting a wound in an animal model. Following topical application, a targeted polycationic photosensitizer conjugate between poly-L-lysine and chlorin(e6) penetrated the gram (-) outer bacterial membrane, and subsequent activation with 660 nm laser light rapidly killed Escherichia coli infecting excisional wounds in mice. To facilitate real-time monitoring of infection, we used bacteria that expressed the lux operon from Photorhabdus luminescens; these cells emitted a bioluminescent signal that allowed the infection to be rapidly quantified, using a low-light imaging system. There was a light-dose dependent loss of luminescence in the wound treated with conjugate and light, not seen in untreated wounds. Treated wounds healed as well as control wounds, showing that the photodynamic treatment did not damage the host tissue. Our study points to the possible use of this methodology in the rapid control of wounds and other localized infections.

Topics: Animals; Chlorophyllides; Escherichia coli Infections; Luminescence; Male; Mice; Mice, Inbred BALB C; Photobiology; Photochemotherapy; Polylysine; Porphyrins; Wound Infection