Abstract
The emergence of multidrug-resistant bacteria has become a real threat and we are fast running out of treatment options. A combinatory strategy is explored here to eradicate multidrug-resistant Staphlococcus aureus and Pseudomonas aeruginosa including planktonic cells, established biofilms, and persisters as high as 7.5 log bacteria in less than 30 min. Blue-laser and thymol together rapidly sterilized acute infected or biofilm-associated wounds and successfully prevented systematic dissemination in mice. Mechanistically, blue-laser and thymol instigated oxidative bursts exclusively in bacteria owing to abundant proporphyrin-like compounds produced in bacteria over mammalian cells, which transformed harmless thymol into blue-laser sensitizers, thymoquinone and thymohydroquinone. Photo-excitations of thymoquinone and thymohydroquinone augmented reactive oxygen species production and initiated a torrent of cytotoxic events in bacteria while completely sparing the host tissue. The investigation unravels a previously unappreciated property of thymol as a pro-photosensitizer analogous to a prodrug that is activated only in bacteria.
Highlights
The emergence of multidrug-resistant bacteria has become a real threat and we are fast running out of treatment options
All bacterial strains used in this study, including four methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, four Pseudomonas aeruginosa (Pa) clinical isolates, one luminescent strain of USA300, and one standard strain of Pa ATCC19660, were confirmed MDR by microbiological tests (Fig. 1a and Supplementary Table 1)
Two dozen of compounds were screened and seven of them were shown in Fig. 1a in which thymol exhibited the most potent bactericidal activities against the MDR strains with a minimal inhibitory concentration (MIC) range from 0.3 mg/mL to 0.8 mg/mL dependent on the bacterial strain tested
Summary
The emergence of multidrug-resistant bacteria has become a real threat and we are fast running out of treatment options. A combinatory strategy is explored here to eradicate multidrug-resistant Staphlococcus aureus and Pseudomonas aeruginosa including planktonic cells, established biofilms, and persisters as high as 7.5 log bacteria in less than 30 min. Essential oils protect plants from phytopathogens and reduce bacterial burdens of MDR pathogens in trauma-associated wounds by targeting the membrane. The combined thymol and BL readily and safely inactivated all forms of bacteria, including planktonic cells, mature biofilms, and persisters of MDR MRSA and Pa strains in vivo and in vitro. The resultant TQ and THQ acted as photosensitizers and magnified ROS productions exponentially and rapidly killed the pathogens while completely sparing the host tissue
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