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A metagenome contains all DNA sequences from an environmental sample, including viruses, bacteria, archaea, and eukaryotes. Since viruses are of huge abundance and have caused vast mortality and morbidity to human society in history as a type of major pathogens, detecting viruses from metagenomes plays a crucial role in analyzing the viral component of samples and is the very first step for clinical diagnosis. However, detecting viral fragments directly from the metagenomes is still a tough issue because of the existence of a huge number of short sequences. In this study a hybrid Deep lEarning model for idenTifying vIral sequences fRom mEtagenomes (DETIRE) is proposed to solve the problem. First, the graph-based nucleotide sequence embedding strategy is utilized to enrich the expression of DNA sequences by training an embedding matrix. Then, the spatial and sequential features are extracted by trained CNN and BiLSTM networks, respectively, to enrich the features of short sequences. Finally, the two sets of features are weighted combined for the final decision. Trained by 220,000 sequences of 500 bp subsampled from the Virus and Host RefSeq genomes, DETIRE identifies more short viral sequences (<1,000 bp) than the three latest methods, such as DeepVirFinder, PPR-Meta, and CHEER. DETIRE is freely available at Github (https://github.com/crazyinter/DETIRE). [ABSTRACT FROM AUTHOR]

Vibrio vulnificus is an invasive marine bacterium that causes a variety of serious infectious diseases. With the increasing multidrug-resistant variants, treatment of V. vulnificus infections is becoming more difficult. In this study, we explored antimicrobial blue light (aBL; 405 nm wavelength) for the treatment of V. vulnificus infections. We first assessed the efficacy of aBL against five strains of V. vulnificus in vitro. Next, we identified and quantified intracellular porphyrins in V. vulnificus to provide mechanistic insights. Additionally, we measured intracellular reactive oxygen species (ROS) production and bacterial membrane permeabilization following aBL exposures. Lastly, we conducted a preclinical study to investigate the efficacy and safety of aBL for the prevention and treatment of burn infections caused by V. vulnificus in mice. We found that aBL effectively killed V. vulnificus in vitro in both planktonic and biofilm states, with up to a 5.17- and 4.57-log10 CFU reduction being achieved, respectively, following an aBL exposure of 216 J/cm2. Protoporphyrin IX and coproporphyrins were predominant in all the strains. Additionally, intracellular ROS was significantly increased following aBL exposures (P < 0.01), and there was evidence of aBL-induced permeabilization of the bacterial membrane (P < 0.0001). In the preclinical studies, we found that female mice treated with aBL 30min after bacterial inoculation showed a survival rate of 81%following 7 days of observation, while only 28% survival was observed in untreated female mice (P < 0.001). At 6 h post-inoculation, an 86% survival was achieved in aBL-treated female mice (P = 0.0002). For male mice, 86 and 63% survival rates were achieved when aBL treatment was given 30min and 6 h after bacterial inoculation, respectively, compared to 32%survival in the untreatedmice (P = 0.0004 and P = 0.04). aBL did not reduce cellular proliferation or induce apoptosis. We found five cytokines were significantly upregulated in the males after aBL treatment, including MCSF (P < 0.001), MCP-5 (P < 0.01), TNF RII (P < 0.01), CXCL1 (P < 0.01), and TIMP-1 (P < 0.05), and one in the females (TIMP-1; P < 0.05), suggesting that aBL may induce certain inflammatory processes. In conclusion, aBL may potentially be applied to prevent and treat V. vulnificus infections. [ABSTRACT FROM AUTHOR]

Background: Biofilms affect >80% bacterial infections in human and are usually difficult to eradicate because of their inherent drug resistance.Methods: We investigated the effectiveness of antimicrobial blue light (aBL) (wavelength, 415 nm) for inactivating Acinetobacter baumannii or Pseudomonas aeruginosa biofilms in 96-well microplates or infected mouse burn wounds.Results: In vitro, in 96-well microplates, exposure of 24-hour-old and 72-hour-old A. baumannii biofilms to 432 J/cm(2) aBL resulted in inactivation of 3.59 log10 and 3.18 log10 colony-forming units (CFU), respectively. For P. aeruginosa biofilms, similar levels of inactivation-3.02 log10 and 3.12 log10 CFU, respectively-were achieved. In mouse burn wounds infected with 5 × 10(6) CFU ofA. baumannii, approximately 360 J/cm(2) and 540 J/cm(2) aBL was required to inactivate 3 log10 CFU in biofilms when delivered 24 and 48 hours, respectively, after bacterial inoculation. High-performance liquid chromatography analysis revealed the presence of endogenous porphyrins in both A. baumannii and P. aeruginosa TUNEL assay detected no apoptotic cells in aBL-irradiated mouse skin at up to 24 hours after aBL exposure (540 J/cm(2)).Conclusions: aBL has antimicrobial activity in biofilms ofA. baumannii and P. aeruginosa and is a potential therapeutic approach for biofilm-related infections. [ABSTRACT FROM AUTHOR]

Background: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT) is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system. Methodology/Principal Findings: In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA) arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT) and preventive (Pre-PDT) effects of PDT using methylene blue as photosensitizer were examined. Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced. With the preconditioning Pre-PDT regimen, neutrophils were quickly accumulated into the joint immediately after bacterial inoculation and bacterial growth was suppressed and the establishment of infection was inhibited. Conclusions/Significance: This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT. [ABSTRACT FROM AUTHOR]