Decrease of ESKAPE virulence with a cationic heme-mimetic gallium porphyrin photosensitizer: The Trojan horse strategy that could help address antimicrobial resistance.

INTRODUCTION: 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. OBJECTIVES: 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. CONCLUSION: 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.

Submerged single-photon LiDAR imaging sensor used for real-time 3D scene reconstruction in scattering underwater environments.

We demonstrate a fully submerged underwater LiDAR transceiver system based on single-photon detection technologies. The LiDAR imaging system used a silicon single-photon avalanche diode (SPAD) detector array fabricated in complementary metal-oxide semiconductor (CMOS) technology to measure photon time-of-flight using picosecond resolution time-correlated single-photon counting. The SPAD detector array was directly interfaced to a Graphics Processing Unit (GPU) for real-time image reconstruction capability. Experiments were performed with the transceiver system and target objects immersed in a water tank at a depth of 1.8 meters, with the targets placed at a stand-off distance of approximately 3 meters. The transceiver used a picosecond pulsed laser source with a central wavelength of 532 nm, operating at a repetition rate of 20 MHz and average optical power of up to 52 mW, dependent on scattering conditions. Three-dimensional imaging was demonstrated by implementing a joint surface detection and distance estimation algorithm for real-time processing and visualization, which achieved images of stationary targets with up to 7.5 attenuation lengths between the transceiver and the target. The average processing time per frame was approximately 33 ms, allowing real-time three-dimensional video demonstrations of moving targets at ten frames per second at up to 5.5 attenuation lengths between transceiver and target.

Staphylococcus aureus from Atopic Dermatitis Patients: Its Genetic Structure and Susceptibility to Phototreatment.

We characterized the population of Staphylococcus aureus from patients with atopic dermatitis (AD) in terms of (i) genetic diversity, (ii) presence and functionality of genes encoding important virulence factors: staphylococcal enterotoxins (sea, seb, sec, sed), toxic shock syndrome 1 toxin (tsst-1), and Panton-Valentine leukocidin (lukS/lukF-PV) by spa typing, PCR, drug resistance profile determination, and Western blot. We then subjected the studied population of S. aureus to photoinactivation based on a light-activated compound called rose bengal (RB) to verify photoinactivation as an approach to effectively kill toxin-producing S. aureus. We have obtained 43 different spa types that can be grouped into 12 clusters, indicating for the first-time clonal complex (CC) 7 as the most widespread. A total of 65% of the tested isolates had at least one gene encoding the tested virulence factor, but their distribution differed between the group of children and adults, and between patients with AD and the control group without atopy. We detected a 3.5% frequency of methicillin-resistant strains (MRSA) and no other multidrug resistance. Despite genetic diversity and production of various toxins, all isolates tested were effectively photoinactivated (bacterial cell viability reduction ≥ 3 log10 units) under safe conditions for the human keratinocyte cell line, which indicates that photoinactivation can be a good option in skin decolonization. IMPORTANCE Staphylococcus aureus massively colonizes the skin of patients with atopic dermatitis (AD). It is worth noting that the frequency of detection of multidrug-resistant S. aureus (MRSA) in AD patients is higher than the healthy population, which makes treatment much more difficult. Information about the specific genetic background of S. aureus accompanying and/or causing exacerbations of AD is of great importance from the point of view of epidemiological investigations and the development of possible treatment options.

Single-photon three-dimensional imaging at up to 10 kilometers range.

Depth and intensity profiling of targets at a range of up to 10 km is demonstrated using time-of-flight time-correlated single-photon counting technique. The system comprised a pulsed laser source at 1550 nm wavelength, a monostatic scanning transceiver and a single-element InGaAs/InP single-photon avalanche diode (SPAD) detector. High-resolution three-dimensional images of various targets acquired over ranges between 800 metres and 10.5 km demonstrate long-range depth and intensity profiling, feature extraction and the potential for target recognition. Using a total variation restoration optimization algorithm, the acquisition time necessary for each pixel could be reduced by at least a factor of ten compared to a pixel-wise image processing approach. Kilometer range depth profiles are reconstructed with average signal returns of less than one photon per pixel.