School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
J Photochem Photobiol B. 2010 Apr 2;99(1):62-6. doi: 10.1016/j.jphotobiol.2010.02.004. Epub 2010 Feb 11.
This study aimed to determine the effect of sub-lethal challenge with Photodynamic Antimicrobial Chemotherapy (PACT) on the susceptibility of clinical Staphylococcus aureus and Pseudomonas aeruginosa isolates to both PACT and a range of antibiotics used in the treatment of infection caused by these bacteria. Clinical S. aureus and P. aeruginosa isolates were exposed to sub-lethal PACT with meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP) and methylene blue (MB) over a 72 h period. After exposure, susceptibility of surviving organisms to a range of antibiotics was determined and compared with the susceptibility of an untreated control. Surviving bacteria were also exposed to previously lethal photosensitizer-light combinations, to determine if susceptibility to PACT was affected by sub-lethal exposure. Exposure to sub-lethal PACT did not decrease susceptibility to antibiotics with the minimum inhibitory concentrations for 95% and 100% of P. aeruginosa and S. aureus isolates, respectively, within two doubling dilutions of the MIC of the untreated control. Similarly, habituation with sub-lethal PACT did not reduce susceptibility of P. aeruginosa isolates to PACT levels previously determined as lethal. A reduction in susceptibility to PACT following habituation was apparent for two S. aureus isolates with MB and for 1 S. aureus isolate with TMP. However, for two of these three isolates, the log reduction for habituated cells was still greater than 4 log(10). PACT remains an attractive potential treatment for infection caused by these bacteria.
本研究旨在确定亚致死光动力抗菌化学疗法 (PACT) 挑战对临床金黄色葡萄球菌和铜绿假单胞菌分离株对 PACT 和治疗这些细菌引起的感染中使用的一系列抗生素的敏感性的影响。将临床分离的金黄色葡萄球菌和铜绿假单胞菌暴露于亚致死剂量的 TMP 和 MB 组成的 PACT 中,持续 72 小时。暴露后,测定存活生物对一系列抗生素的敏感性,并与未经处理的对照物进行比较。还将幸存细菌暴露于先前致死的光生物剂-光组合中,以确定亚致死暴露是否会影响对 PACT 的敏感性。亚致死 PACT 暴露并未降低抗生素的敏感性,铜绿假单胞菌和金黄色葡萄球菌分离株的最小抑菌浓度(MIC)分别为 95%和 100%,而未经处理的对照物的 MIC 则为两倍。同样,亚致死 PACT 习服也不会降低铜绿假单胞菌分离株对先前确定为致死水平的 PACT 的敏感性。在 MB 对两株金黄色葡萄球菌和 TMP 对 1 株金黄色葡萄球菌的亚致死 PACT 之后,对 PACT 的敏感性降低。然而,对于这三个分离株中的两个,习服细胞的对数减少仍大于 4 log(10)。PACT 仍然是治疗这些细菌引起的感染的一种有吸引力的潜在治疗方法。