Dataset Information

Bacteria-specific pro-photosensitizer kills multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

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.

SUBMITTER: Lu M

PROVIDER: S-EPMC7994569 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Bacteria-specific pro-photosensitizer kills multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

Lu Min M Li Yongli Y Wu Mei X MX

Communications biology 20210325 1

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 disseminatio ...[more]

PMID: 33767385

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Project description:BackgroundWe aimed to identify the main spreading clones, describe the resistance mechanisms associated with carbapenem- and/or multidrug-resistant P. aeruginosa and characterize patients at risk of acquiring these strains in Estonian hospitals.MethodsNinety-two non-duplicated carbapenem- and/or multidrug-resistant P. aeruginosa strains were collected between 27th March 2012 and 30th April 2013. Clinical data of the patients was obtained retrospectively from the medical charts. Clonal relationships of the strains were determined by whole genome sequencing and analyzed by multi-locus sequence typing. The presence of resistance genes and beta-lactamases and their origin was determined. Combined-disk method and PCR was used to evaluate carbapenemase and metallo-beta-lactamase production.ResultsForty-three strains were carbapenem-resistant, 11 were multidrug-resistant and 38 were both carbapenem- and multidrug-resistant. Most strains (54%) were isolated from respiratory secretions and caused an infection (74%). Over half of the patients (57%) were ≥ 65 years old and 85% had ≥1 co-morbidity; 96% had contacts with healthcare and/or had received antimicrobial treatment in the previous 90 days. Clinically relevant beta-lactamases (OXA-101, OXA-2 and GES-5) were found in 12% of strains, 27% of which were located in plasmids. No Ambler class B beta-lactamases were detected. Aminoglycoside modifying enzymes were found in 15% of the strains. OprD was defective in 13% of the strains (all with CR phenotype); carbapenem resistance triggering mutations (F170 L, W277X, S403P) were present in 29% of the strains. Ciprofloxacin resistance correlated well with mutations in topoisomerase genes gyrA (T83I, D87N) and parC (S87 L). Almost all strains (97%) with these mutations showed ciprofloxacin-resistant phenotype. Multi-locus sequence type analysis indicated high diversity at the strain level - 36 different sequence types being detected. Two sequence types (ST108 (n = 23) and ST260 (n = 18)) predominated. Whereas ST108 was associated with localized spread in one hospital and mostly carbapenem-resistant phenotype, ST260 strains occurred in all hospitals, mostly with multi-resistant phenotype and carried different resistance genotype/machinery.ConclusionsDiverse spread of local rather than international P. aeruginosa strains harboring multiple chromosomal mutations, but not plasmid-mediated Ambler class B beta-lactamases, were found in Estonian hospitals.Trial registrationThis trial was registered retrospectively in ClinicalTrials.gov ( NCT03343119 ).

Dataset Information

Bacteria-specific pro-photosensitizer kills multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

Publications

Bacteria-specific pro-photosensitizer kills multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

Similar Datasets

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