Antimicrobial Biophotonic Treatment of Ampicillin-Resistant Pseudomonas aeruginosa with Hypericin and Ampicillin Cotreatment Followed by Orange Light

Abstract

Bacterial antibiotic resistance is an alarming global issue that requires alternative antimicrobial methods to which there is no resistance. Antimicrobial photodynamic therapy (APDT) is a well-known method to combat this problem for many pathogens, especially Gram-positive bacteria and fungi. Hypericin and orange light APDT efficiently kill Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and the yeast Candida albicans. Although Gram-positive bacteria and many fungi are readily killed with APDT, Gram-negative bacteria are difficult to kill due to their different cell wall structures. Pseudomonas aeruginosa is one of the most important opportunistic, life-threatening Gram-negative pathogens. However, it cannot be killed successfully by hypericin and orange light APDT. P. aeruginosa is ampicillin resistant, but we hypothesized that ampicillin could still damage the cell wall, which can promote photosensitizer uptake into Gram-negative cells. Using hypericin and ampicillin cotreatment followed by orange light, a significant reduction (3.4 log) in P. aeruginosa PAO1 was achieved. P. aeruginosa PAO1 inactivation and gut permeability improvement by APDT were successfully shown in a Caenorhabditis elegans model.

Anti‐staphylococcal activity of a cyclic lipopeptide, C 15 ‐bacillomycin D, produced by Bacillus velezensis NST6

“…2017; Alam et al . 2019). Caenorhabditis elegans strain N2 and E. coli OP50 were obtained from the Caenorhabditis Genetics Center (CGC, Minneapolis, MN) and S. aureus KCTC 3881 from the Korean Collections for Type Cultures (KCTC, Jeongeup, Korea).…”

Antimicrobial Photoinactivation Approach Based on Natural Agents for Control of Bacteria Biofilms in Spacecraft

“…As shown in Figure 4, upon light activation, at low concentrations, Hyp is efficient primarily in the generation of singlet oxygen (Type II mechanism), whereas, at high concentrations, it produces superoxide anion (Type I mechanism) [99]. Hyp (or its derivatives)-based API can induce death of Gram-positive methicillin-susceptible S. aureus (MSSA) and MRSA cells [100][101][102][103][104][105][106][107][108][109][110]. Hyp-mediated photoinactivation is reported to be more effective against planktonic S. aureus than against its biofilms [105][106][107].…”

“…It is known that Hyp is a neutral hydrophobic PS. Therefore, it does not simply get into Gram-negative bacteria such as E. coli [106,108,110,114,115], P. aeruginosa [100,106], and Salmonella enterica [112]. De Melo et al (2013) used electroporation to increase the uptake of Hyp, thus enhancing the inactivation of E. coli to 3.5 logs [108].…”

“…Hyp (or its derivatives)-based API can induce death of Gram-positive methicillin-susceptible S. aureus (MSSA) and MRSA cells [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ]. Hyp-mediated photoinactivation is reported to be more effective against planktonic S. aureus than against its biofilms [ 105 , 106 , 107 ].…”

“…Furthermore, the required illumination doses have to be discussed and compared with general illumination conditions. RF can be excited by blue light and requires from 3 to 400 J/cm 2 according to the data available in the literature (see Table S1 of Supplementary Material ) [ 93 , 94 , 95 , 96 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 117 , 118 , 119 , 120 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 148 , 149 , 150 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 165 , 173 , 175 , 176 , 177 , 178 , 179 , 180 , 181 ,…”