Affiliation:
1. Wellman Laboratories of Photomedicine, Massachusetts General Hospital, and Department of Dermatology, Harvard Medical School, Boston, Massachusetts
Abstract
ABSTRACT
The emergence of antibiotic resistance among pathogenic bacteria has led to efforts to find alternative antimicrobial therapeutics to which bacteria will not be easily able to develop resistance. One of these may be the combination of nontoxic dyes (photosensitizers [PS]) and visible light, known as photodynamic therapy, and we have reported its use to treat localized infections in animal models. While it is known that gram-positive species are generally susceptible to photodynamic inactivation (PDI), the factors that govern variation in degrees of killing are unknown. We used isogenic pairs of wild-type and transposon mutants deficient in capsular polysaccharide and slime production generated from
Staphylococcus epidermidis
and
Staphylococcus aureus
to examine the effects of extracellular slime on susceptibility to PDI mediated by two cationic PS (a polylysine-chlorin
e6
conjugate, pL-c
e6
, and methylene blue [MB]) and an anionic molecule, free c
e6
, and subsequent exposure to 665-nm light at 0 to 40 J/cm
2
. Free c
e6
gave more killing of mutant strains than wild type, despite the latter taking up more PS. Log-phase cultures were killed more than stationary-phase cultures, and this correlated with increased uptake. The cationic pL-c
e6
and MB gave similar uptakes and killing despite a 50-fold difference in incubation concentration. Differences in susceptibility between strains and between growth phases observed with free c
e6
largely disappeared with the cationic compounds despite significant differences in uptake. These data suggest that slime production and stationary phase can be obstacles against PDI for gram-positive bacteria but that these obstacles can be overcome by using cationic PS.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
160 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献