Abstract
Photodynamic inactivation (PDI) is a non-antibiotic option for the treatment of infectious diseases. Although Gram-positive bacteria have been shown to be highly susceptible to PDI, the inactivation of Gram-negative bacteria has been more challenging due to the impermeability properties of the outer membrane. In the present study, a series of photosensitizers which contain one to four positive charges (1–4) were used to evaluate the charge influence on the PDI of a Gram-negative bacteria, Escherichia coli (E. coli), and their interaction with the cell membrane. The dose-response PDI results confirm the relevance of the number of positive charges on the porphyrin molecule in the PDI of E. coli. The difference between the Hill coefficients of cationic porphyrins with 1–3 positive charges and the tetra-cationic porphyrin (4) revealed potential variations in their mechanism of inactivation. Fluorescent live-cell microscopy studies showed that cationic porphyrins with 1–3 positive charges bind to the cell membrane of E. coli, but are not internalized. On the contrary, the tetra-cationic porphyrin (4) permeates through the membrane of the cells. The contrast in the interaction of cationic porphyrins with E. coli confirmed that they followed different mechanisms of inactivation. This work helps to have a better understanding of the structure-activity relationship in the efficiency of the PDI process of cationic porphyrins against Gram-negative bacteria.
Highlights
Since the discovery of antibiotics, treatment of bacterial infections has become increasingly difficult due to antibiotic resistance
The results in this study confirmed that the number of cationic groups on porphyrins has a major impact on the Photodynamic inactivation of microbes (PDI) of E. coli
The dose-response graph showed that the PDI efficiency of the porphyrins against E. coli was directly correlated with the number of positive charges following the order: 5 < 1 < 2 < 3; this trend is not followed by compounds 4 and 6
Summary
Since the discovery of antibiotics, treatment of bacterial infections has become increasingly difficult due to antibiotic resistance. The presence of antibiotic resistant bacteria has led to an increase in infections, healthcare costs and deaths throughout the world [1]. Photodynamic inactivation of microbes (PDI) is a non-antibiotic alternative treatment that uses light, a photosensitizer (PS), and molecular oxygen to create reactive oxygen species (ROS) such as singlet oxygen (1O2), superoxide and hydroxyl radicals [2,3,4,5,6,7,8,9]. In PDI, the type II mechanism of photochemical reactions, which is associated with the generation of 1O2,. OIln. SPci.D20I,19t,h2e0, 1t3y4pe II mechanism of photochemical reactions, which is associated with otfh1e8 generation of 1O2, is usually the major pathway in cellular oxidative damage of bacteria [10,11]. Hthoewamevpehr,ipohthileirc fparcotopresrtsiueschofasthtehetrci-eclal tmioenmicbdraenrieviantitvereasc[t2io3]n. aHnodwinevteerrn, aoltihzeartifoanctcoarns asulscohpalsaythaercoellel tmoeamccboruanntefionrtethraocsteiornesaunldts.internalization can play a role to account for those results
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