期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：36
DOI：10.1073/pnas.2208378119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Antimicrobial-resistant bacteria (ARB) are a present and growing healthcare threat, especially for hospitalized patients where nosocomial infections constitute a growing concern. Methicillin-resistant
Staphylococcus aureus (MRSA), for example, has posed a significant risk for hospital-associated illness since its discovery (M. P. Jevons, 1961). The tools most used to fight resistant pathogens involve multiple antibiotics, synthetic antibiotic hybrids, or a combination with an adjuvant to increase susceptibility. Utilization of antimicrobial photodynamic therapy (aPDT) provides nonspecific impairment of resistance mechanisms, diversifying the appropriate antibiotics and reducing necessary doses. Here, combined aPDT and antibiotic treatment is demonstrated in vitro against multiple MRSA strains, yielding increased antibiotic susceptibility. This presents an opportunity to extend the efficacious lifetime of existing antibiotics.
The widespread use of antibiotics drives the evolution of antimicrobial-resistant bacteria (ARB), threatening patients and healthcare professionals. Therefore, the development of novel strategies to combat resistance is recognized as a global healthcare priority. The two methods to combat ARB are development of new antibiotics or reduction in existing resistances. Development of novel antibiotics is a laborious and slow-progressing task that is no longer a safe reserve against looming risks. In this research, we suggest a method for reducing resistance to extend the efficacious lifetime of current antibiotics. Antimicrobial photodynamic therapy (aPDT) is used to generate reactive oxygen species (ROS) via the photoactivation of a photosensitizer. ROS then nonspecifically damage cellular components, leading to general impairment and cell death. Here, we test the hypothesis that concurrent treatment of bacteria with antibiotics and aPDT achieves an additive effect in the elimination of ARB. Performing aPDT with the photosensitizer methylene blue in combination with antibiotics chloramphenicol and tetracycline results in significant reductions in resistance for two methicillin-resistant
Staphylococcus aureus (MRSA) strains, USA300 and RN4220. Additional resistant
S. aureus strain and antibiotic combinations reveal similar results. Taken together, these results suggest that concurrent aPDT consistently decreases
S. aureus resistance by improving susceptibility to antibiotic treatment. In turn, this development exhibits an alternative to overcome some of the growing MRSA challenge.
关键词：enphotodynamic therapyantibiotic resistanceantimicrobial-resistant bacteriamethicillin-resistantStaphylococcus aureusmethylene blue
