Dos Anjos Carolina, Wang Yin, Truong-Bolduc Que Chi, Bolduc Paul K, Liu Matthew, Hooper David C, Anderson R Rox, Dai Tianhong, Leanse Leon G
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Division of Infectious Diseases and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Lasers Surg Med. 2024 Sep;56(7):673-681. doi: 10.1002/lsm.23819. Epub 2024 Jul 22.
In this study, we evaluated the effectiveness of antimicrobial blue light (aBL; 410 nm wavelength) against β-lactamase-carrying bacteria and the effect of aBL on the activity of β-lactamases.
Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae strains carrying β-lactamases as well as a purified β-lactamase enzymes were studied. β-lactamase activity was assessed using a chromogenic cephalosporin hydrolysis assay. Additionally, we evaluated the role of porphyrins in the photoreaction, as well as protein degradation by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Finally, we investigated the bactericidal effect of combined aBL-ceftazidime exposure against a metallo-β-lactamase expressing P. aeruginosa strain.
Our study demonstrated that aBL effectively killed β-lactamase-producing bacteria and reduced β-lactamase activity. After an aBL exposure of 1.52 J/cm, a 50% reduction in enzymatic activity was observed in P. aeruginosa. Additionally, we found a 40% decrease in the photoreaction activity of porphyrins following an aBL exposure of 64.8 J/cm. We also revealed that aBL reduced β-lactamase activity via protein degradation (after 136.4 J/cm). Additionally, aBL markedly improved the bactericidal effect of ceftazidime (by >4-log) in the metallo-β-lactamase P. aeruginosa strain.
Our results provide evidence that aBL compromises bacterial β-lactamase activity, offering a potential approach to overcome β-lactam resistance in bacteria.
在本研究中,我们评估了抗菌蓝光(aBL;波长410nm)对携带β-内酰胺酶细菌的有效性以及aBL对β-内酰胺酶活性的影响。
研究了携带β-内酰胺酶的铜绿假单胞菌、大肠杆菌和肺炎克雷伯菌菌株以及纯化的β-内酰胺酶。使用显色头孢菌素水解试验评估β-内酰胺酶活性。此外,我们评估了卟啉在光反应中的作用,以及通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)进行的蛋白质降解。最后,我们研究了联合aBL-头孢他啶暴露对表达金属β-内酰胺酶的铜绿假单胞菌菌株的杀菌效果。
我们的研究表明,aBL能有效杀死产生β-内酰胺酶的细菌并降低β-内酰胺酶活性。在aBL暴露1.52J/cm²后,观察到铜绿假单胞菌的酶活性降低了50%。此外,我们发现aBL暴露64.8J/cm²后,卟啉的光反应活性降低了40%。我们还发现aBL通过蛋白质降解降低β-内酰胺酶活性(在136.4J/cm²之后)。此外,aBL显著提高了头孢他啶对金属β-内酰胺酶铜绿假单胞菌菌株的杀菌效果(提高了>4个对数)。
我们的结果提供了证据,表明aBL会损害细菌的β-内酰胺酶活性,为克服细菌中的β-内酰胺耐药性提供了一种潜在方法。