Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies

Autor: Yao Yuan, Heng Jin, Ziquan Liu, Tian-Jun Liu, Shi Sun, Haojun Fan, Wang Xue, Hui Ding, Shike Hou
Rok vydání: 2016
Předmět:
0301 basic medicine
Acinetobacter baumannii
Light
Physiology
lcsh:Medicine
Drug resistance
Pathology and Laboratory Medicine
Mice
Anti-Infective Agents
Animal Cells
Antibiotics
Antimicrobial chemotherapy
Medicine and Health Sciences
Amino Acids
lcsh:Science
Immune Response
Connective Tissue Cells
Multidisciplinary
biology
Chemistry
Antimicrobials
Organic Compounds
Drugs
Connective Tissue
Physical Sciences
Cellular Types
Anatomy
Research Article
Porphyrins
030106 microbiology
Immunology
Pact
Microbiology
03 medical and health sciences
Antibiotic resistance
Signs and Symptoms
In vivo
Diagnostic Medicine
Microbial Control
Drug Resistance
Bacterial
Tissue Repair
Animals
Humans
Inflammation
Pharmacology
Wound Healing
lcsh:R
Organic Chemistry
Chemical Compounds
Biology and Life Sciences
Cell Biology
Fibroblasts
biology.organism_classification
In vitro
Multiple drug resistance
030104 developmental biology
Biological Tissue
Photochemotherapy
lcsh:Q
Antimicrobial Resistance
Physiological Processes
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 5, p e0176529 (2017)
ISSN: 1932-6203
Popis: Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective therapeutic modality to eradicate drug resistant bacteria without provoking multidrug resistance, has attracted increasing attention. This study examined the antimicrobial efficacy of the novel cationic amino acid-porphyrin conjugate 4I with four lysine groups against two different clinical isolated strains (drug sensitive and multidrug resistant) of the Acinetobacter baumannii species and its toxicity on murine dermal fibroblasts in vitro, as well as the therapeutic effect of PACT on acute, potentially lethal multidrug resistant strain excisional wound infections in vivo. The PACT protocol exposed 4I to illumination, exhibiting high antimicrobial efficacy on two different strains due to a high yield of reactive oxygen species (ROS) and non-selectivity to microorganisms. The photoinactivation effects of 4I against two different strains were dose-dependent. At 3.9 μM and 7.8 μM, PACT induced 6 log units of inactivation of sensitive and multidrug resistant strains. In contrast, 4I alone and illumination alone treatments had no visibly antimicrobial effect. Moreover, cytotoxicity tests revealed the great safety of the photosensitizer 4I in mice. In the in vivo study, we found 4I-mediated PACT was not only able to kill bacteria but also accelerated wound recovery. Compared with non-treated mice, over 2.89 log reduction of multidrug resistant Acinetobacter baumannii strain was reached in PACT treat mice at 24 h post-treatment. These results imply that 4I-mediated PACT therapy is an effective and safe alternative to conventional antibiotic therapy and has clinical potential for superficial drug-resistant bacterial infections.
Databáze: OpenAIRE
Externí odkaz: