Abstract：
BACKGROUND: Emerging antibiotic resistance among bacterial pathogens has forced an urgent need for alternative non-antibiotic strategies development that could combat drug resistant-associated infections. Suppression of virulence of ESKAPE pathogens\' by targeting multiple virulence traits provides a promising approach.
OBJECTIVE: Here we propose an iron-blocking antibacterial therapy based on a cationic heme-mimetic gallium porphyrin (GaCHP), which antibacterial efficacy could be further enhanced by photodynamic inactivation.
METHODS: We used gallium heme mimetic porphyrin (GaCHP) excited with light to significantly reduce microbial viability and suppress both the expression and biological activity of several virulence traits of both Gram-positive and Gram-negative ESKAPE representatives, i.e., S. aureus and P. aeruginosa. Moreover, further improvement of the proposed strategy by combining it with routinely used antimicrobials to resensitize the microbes to antibiotics and provide enhanced bactericidal efficacy was investigated.
RESULTS: The proposed strategy led to substantial inactivation of critical priority pathogens and has been evidenced to suppress the expression and biological activity of multiple virulence factors in S. aureus and P. aeruginosa. Finally, the combination of GaCHP phototreatment and antibiotics resulted in promising strategy to overcome antibiotic resistance of the studied microbes and to enhance disinfection of drug resistant pathogens.
CONCLUSIONS: Lastly, considering high safety aspects of the proposed treatment toward host cells, i.e., lack of mutagenicity, no dark toxicity and mild phototoxicity, we describe an efficient alternative that simultaneously suppresses the functionality of multiple virulence factors in ESKAPE pathogens.
OBJECTIVE: Here we propose an iron-blocking antibacterial therapy based on a cationic heme-mimetic gallium porphyrin (GaCHP), which antibacterial efficacy could be further enhanced by photodynamic inactivation.
METHODS: We used gallium heme mimetic porphyrin (GaCHP) excited with light to significantly reduce microbial viability and suppress both the expression and biological activity of several virulence traits of both Gram-positive and Gram-negative ESKAPE representatives, i.e., S. aureus and P. aeruginosa. Moreover, further improvement of the proposed strategy by combining it with routinely used antimicrobials to resensitize the microbes to antibiotics and provide enhanced bactericidal efficacy was investigated.
RESULTS: The proposed strategy led to substantial inactivation of critical priority pathogens and has been evidenced to suppress the expression and biological activity of multiple virulence factors in S. aureus and P. aeruginosa. Finally, the combination of GaCHP phototreatment and antibiotics resulted in promising strategy to overcome antibiotic resistance of the studied microbes and to enhance disinfection of drug resistant pathogens.
CONCLUSIONS: Lastly, considering high safety aspects of the proposed treatment toward host cells, i.e., lack of mutagenicity, no dark toxicity and mild phototoxicity, we describe an efficient alternative that simultaneously suppresses the functionality of multiple virulence factors in ESKAPE pathogens.
摘要：
背景：细菌病原体中出现的抗生素耐药性迫使迫切需要开发替代的非抗生素策略来对抗耐药相关感染。通过靶向多种毒力性状来抑制ESKAPE病原体的毒力提供了一种有希望的方法。
目的：在这里，我们提出了一种基于阳离子血红素模拟镓卟啉（GaCHP）的铁阻断抗菌疗法，光动力灭活可以进一步提高抗菌效果。
方法：我们使用光激发的镓血红素模拟卟啉（GaCHP）显着降低微生物活力并抑制革兰氏阳性和革兰氏阴性ESKAPE代表的几种毒力性状的表达和生物学活性。即，金黄色葡萄球菌和铜绿假单胞菌。此外，研究了通过将其与常规使用的抗微生物剂结合以使微生物对抗生素重新敏感并提供增强的杀菌效果来进一步改进所提出的策略.
结果：所提出的策略导致关键优先病原体的大量失活，并已被证明抑制金黄色葡萄球菌和铜绿假单胞菌中多种毒力因子的表达和生物活性。最后,GaCHP光治疗和抗生素的结合产生了有希望的策略，以克服所研究微生物的抗生素耐药性，并加强耐药性病原体的消毒。
结论：最后，考虑到针对宿主细胞的拟议治疗的高安全性方面，即，缺乏致突变性，无暗毒性和轻度光毒性，我们描述了一种同时抑制ESKAPE病原体中多种毒力因子功能的有效替代方案.
目的：在这里，我们提出了一种基于阳离子血红素模拟镓卟啉（GaCHP）的铁阻断抗菌疗法，光动力灭活可以进一步提高抗菌效果。
方法：我们使用光激发的镓血红素模拟卟啉（GaCHP）显着降低微生物活力并抑制革兰氏阳性和革兰氏阴性ESKAPE代表的几种毒力性状的表达和生物学活性。即，金黄色葡萄球菌和铜绿假单胞菌。此外，研究了通过将其与常规使用的抗微生物剂结合以使微生物对抗生素重新敏感并提供增强的杀菌效果来进一步改进所提出的策略.
结果：所提出的策略导致关键优先病原体的大量失活，并已被证明抑制金黄色葡萄球菌和铜绿假单胞菌中多种毒力因子的表达和生物活性。最后,GaCHP光治疗和抗生素的结合产生了有希望的策略，以克服所研究微生物的抗生素耐药性，并加强耐药性病原体的消毒。
结论：最后，考虑到针对宿主细胞的拟议治疗的高安全性方面，即，缺乏致突变性，无暗毒性和轻度光毒性，我们描述了一种同时抑制ESKAPE病原体中多种毒力因子功能的有效替代方案.
