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Frontiers in Cellular and Infection... 2023Over the last few decades, a growing body of evidence has suggested a role for various infectious agents in Alzheimer's disease (AD) pathogenesis. Despite diverse...
BACKGROUND
Over the last few decades, a growing body of evidence has suggested a role for various infectious agents in Alzheimer's disease (AD) pathogenesis. Despite diverse pathogens (virus, bacteria, fungi) being detected in AD subjects' brains, research has focused on individual pathogens and only a few studies investigated the hypothesis of a bacterial brain microbiome. We profiled the bacterial communities present in non-demented controls and AD subjects' brains.
RESULTS
We obtained postmortem samples from the brains of 32 individual subjects, comprising 16 AD and 16 control age-matched subjects with a total of 130 samples from the frontal and temporal lobes and the entorhinal cortex. We used full-length 16S rRNA gene amplification with Pacific Biosciences sequencing technology to identify bacteria. We detected bacteria in the brains of both cohorts with the principal bacteria comprising (formerly ) and two species each of and genera. We used a hierarchical Bayesian method to detect differences in relative abundance among AD and control groups. Because of large abundance variances, we also employed a new analysis approach based on the Latent Dirichlet Allocation algorithm, used in computational linguistics. This allowed us to identify five sample classes, each revealing a different microbiota. Assuming that samples represented infections that began at different times, we ordered these classes in time, finding that the last class exclusively explained the existence or non-existence of AD.
CONCLUSIONS
The AD-related pathogenicity of the brain microbiome seems to be based on a complex polymicrobial dynamic. The time ordering revealed a rise and fall of the abundance of with pathogenicity occurring for an off-peak abundance level in association with at least one other bacterium from a set of genera that included , , , , and . may also be involved with outcompeting the species, which were strongly associated with non-demented brain microbiota, whose early destruction could be the first stage of disease. Our results are also consistent with a leaky blood-brain barrier or lymphatic network that allows bacteria, viruses, fungi, or other pathogens to enter the brain.
Topics: Humans; Alzheimer Disease; RNA, Ribosomal, 16S; Bayes Theorem; Microbiota; Bacteria; Propionibacterium acnes; Brain; Acne Vulgaris
PubMed: 37780846
DOI: 10.3389/fcimb.2023.1123228 -
Scientific Reports Sep 2023The bacteriophage CAP 10-3 forming plaques against Cutibacterium acnes which causes skin acne was previously isolated from human skin acne lesion. Incomplete whole...
The bacteriophage CAP 10-3 forming plaques against Cutibacterium acnes which causes skin acne was previously isolated from human skin acne lesion. Incomplete whole genome sequence (WGS) of the bacteriophage CAP 10-3 was obtained and it had 29,643 bp long nucleotide with 53.86% GC content. The sequence was similar to C. acnes phage PAP 1-1 with a nucleotide sequence identity of 89.63% and the bacteriophage belonged to Pahexavirus. Bioinformatic analysis of the WGS predicted 147 ORFs and functions of 40 CDSs were identified. The predicted endolysin gene of bacteriophage CAP 10-3 was 858 bp long which was deduced as 285 amino acids (~ 31 kDa). The protein had the highest similarity with amino acid sequence of the endolysin from Propionibacterium phage PHL071N05 with 97.20% identity. The CAP 10-3 endolysin gene was amplified by PCR with primer pairs based on the gene sequence, cloned into an expression vector pET-15b and transformed into Escherichia coli BL21(DE3) strain. The predicted protein band (~ 33 kDa) for the recombinant endolysin was detected in an SDS-PAGE gel and western blot assay. The concentrated supernatant of cell lysate from E. coli BL21(DE3) (pET-15b_CAP10-3 end) and a partially purified recombinant CAP 10-3 endolysin showed antibacterial activity against C. acnes KCTC 3314 in a dose-dependent manner. In conclusion, the recombinant CAP 10-3 endolysin was successfully produced in E. coli strain and it can be considered as a therapeutic agent candidate for treatment of human skin acne.
Topics: Humans; Bacteriophages; Escherichia coli; Endopeptidases; Acne Vulgaris
PubMed: 37777575
DOI: 10.1038/s41598-023-43559-z -
International Journal of Molecular... Sep 2023Although dry eye disease (DED) is one of the most common ocular surface diseases worldwide, its pathogenesis is incompletely understood, and treatment options are...
Although dry eye disease (DED) is one of the most common ocular surface diseases worldwide, its pathogenesis is incompletely understood, and treatment options are limited. There is growing evidence that complex interactions between the ocular surface microbiome (OSM) and tear fluid constituents, potentially leading to inflammatory processes, are associated with ocular surface diseases such as DED. In this study, we aimed to find unique compositional and functional features of the OSM associated with human and microbial tear proteins in patients with DED. Applying whole-metagenome shotgun sequencing of forty lid and conjunctival swabs, we identified 229 taxa, with Actinobacteria and Proteobacteria being the most abundant phyla and Propionibacterium acnes the dominating species in the cohort. When DED patients were compared to controls, the species Corynebacterium tuberculostearicum was more abundant in conjunctival samples, whereas the family Propionibacteriaceae was more abundant in lid samples. Functional analysis showed that genes of L-lysine biosynthesis, tetrapyrrole biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis, and the super pathway of L-threonine biosynthesis were enriched in conjunctival samples of controls. The relative abundances of Acinetobacter johnsonii correlated with seven human tear proteins, including mucin-16. The three most abundant microbial tear proteins were the chaperone protein DnaK, the arsenical resistance protein ArsH, and helicase. Compositional and functional features of the OSM and the tear proteome are altered in patients with DED. Ultimately, this may help to design novel interventional therapeutics to target DED.
Topics: Humans; Proteome; Eye; Dry Eye Syndromes; Face; Microbiota
PubMed: 37762390
DOI: 10.3390/ijms241814091 -
Marine Drugs Aug 2023The protein extract of hydrolyzed with Alcalase and Flavourzyme was found to have multi-functional properties, including total antioxidant capacity (TAC), collagenase...
The protein extract of hydrolyzed with Alcalase and Flavourzyme was found to have multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory, and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of hydrolysate from cation-exchange chromatography displayed significantly high TAC, collagenase inhibitory, and antibacterial effects against , and only the Q3 fraction from anion-exchange chromatography displayed high multi-functional activities. Eight of 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results for screening with molecular docking on target proteins and were then synthesized. Thr-Gly-Thr-Trp (TGTW) displayed ABTS [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. The effect of TAC as Trolox equivalence was dependent on the concentration of TGTW. Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) exhibited collagenase inhibitory activity, which increased according to the increase in concentration, and their IC values were 0.95 mM and 0.84 mM, respectively. Peptides RDRF and His-Ala-Val-Tyr (HAVY) displayed anti- effects, with IC values of 8.57 mM and 13.23 mM, respectively. These results suggest that the hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics.
PubMed: 37755082
DOI: 10.3390/md21090469 -
Scientific Reports Sep 2023Cutibacterium acnes (C. acnes) is one of the most prevalent bacteria that forms the human skin microbiota. Specific phylotypes of C. acnes have been associated with the...
Cutibacterium acnes (C. acnes) is one of the most prevalent bacteria that forms the human skin microbiota. Specific phylotypes of C. acnes have been associated with the development of acne vulgaris, while other phylotypes have been linked to healthy skin. In this scenario, bacterial extracellular vesicles (EVs) play a role in the interkingdom communication role with the human host. The purpose of this study was to examine the impact of EVs generated by various phylotypes of C. acnes on inflammation and sebum production using different in vitro skin cell types. The main findings of this study reveal that the proteomic profile of the cargo embodied in the EVs reflects distinct characteristics of the different C. acnes phylotypes in terms of life cycle, survival, and virulence. The in vitro skin cell types showed an extended pro-inflammatory modulation of SLST A1 EVs consistently triggering the activation of the inflammation-related factors IL-8, IL-6, TNFα and GM-CSF, in comparison to SLST H1 and SLST H2. Additionally, an acne-prone skin model utilizing PCi-SEB and arachidonic acid as a sebum inducer, was employed to investigate the impact of C. acnes EVs on sebum regulation. Our findings indicated that all three types of EVs significantly inhibited sebum production after a 24-h treatment period, with SLST H1 EVs exhibiting the most pronounced inhibitory effect when compared to the positive control. The results of this study highlight the protective nature of C. acnes SLST H1 EVs and their potential use as a natural treatment option for alleviating symptoms associated with inflammation and oily skin.
Topics: Humans; Proteomics; Skin; Skin Diseases; Extracellular Vesicles; Acne Vulgaris; Propionibacterium acnes; Factor VIII; Inflammation
PubMed: 37749255
DOI: 10.1038/s41598-023-43354-w -
International Orthopaedics Feb 2024Bone and joint infections are an important and increasing problem. Whether intraoperatively detected bacteria should be considered relevant or not is often difficult to...
PURPOSE
Bone and joint infections are an important and increasing problem. Whether intraoperatively detected bacteria should be considered relevant or not is often difficult to assess. This retrospective cohort study analyzes the relevance of C. acnes cultured from deep intraoperative specimens.
METHODS
All deep tissue samples collected intraoperatively between 2015 and 2020 from a quartiary care provider were evaluated for detection of C. acnes and its therapeutical consequences. Infection rates were determined according to a standardized definition and protocol and analyzed in dependence of patient's demographic data (age and gender), operative parameters (type of surgery, body region/location of surgery, and impression of the surgeon), and initiated therapy.
RESULTS
In 270 cases of more than 8500 samples, C. acnes was detected. In 30%, the detection was considered an infection. The number of samples taken and tested positive for C. acnes correlated significantly with its classification as a cause of infection. If more than one sample of the patient was positive, the detection was significantly more likely to be treated as infection (p < 0.001). In 76% of cases, a consultation to the infectious diseases (ID) department took place regarding the classification of the pathogen detection and the therapy to be carried out. Almost all of the tested isolates demonstrated the wild-type susceptibility for penicillin and clindamycin.
CONCLUSION
Intraoperative detection of skin-colonizing bacteria such as C. acnes is not always synonymous with infection. In particular, if other examination results contradict an infection (pathological sample without evidence of an infectious event, detection of malignant cells, etc.), the situation must be considered in a very differentiated manner. Interdisciplinary boards, for example, are suitable for this purpose. Care should be taken to obtain a sufficiently large number of tissue samples for microbiological examination to be able to better classify the result.
Topics: Humans; Retrospective Studies; Propionibacterium acnes; Orthopedic Procedures; Arthritis, Infectious; Skin; Gram-Positive Bacterial Infections; Shoulder Joint
PubMed: 37730929
DOI: 10.1007/s00264-023-05981-w -
Cureus Aug 2023Propionibacterium acnes (P. acnes) is a slow-growing, anaerobic, gram-positive bacillus that commonly colonizes the skin and is a rare cause of CNS infections. It was...
Peculiar Case of Brain Abscess Caused by Propionibacterium acnes in an Immunocompetent Individual Without Prior Neurosurgical Intervention: A Case Report and Literature Review.
Propionibacterium acnes (P. acnes) is a slow-growing, anaerobic, gram-positive bacillus that commonly colonizes the skin and is a rare cause of CNS infections. It was previously viewed as a culture contaminant but is now recognized to infrequently cause indolent cases of CNS infections. It is even more rarely associated with abscesses in patients without a prior history of neurosurgical intervention. Due to being a slow-growing bacteria, P. acnes is frequently discovered to be the causative organism after 16S rRNA sequencing. In this case, the culture was positive. There are only five other reported cases of patients with a P. acnes abscess without prior neurosurgical intervention. Here we present the sixth case of an immunocompetent young male who was found to have a P. acnes brain abscess.
PubMed: 37724199
DOI: 10.7759/cureus.43647 -
Journal of Chest Surgery Nov 2023We report a case of chest wall resection for painful chest wall nonunion, 5 years after traumatic flail chest and a first attempt at surgical treatment. The decision was...
We report a case of chest wall resection for painful chest wall nonunion, 5 years after traumatic flail chest and a first attempt at surgical treatment. The decision was made to perform surgery again after 2 years of unsuccessful well-conducted analgesic treatment. During surgery, we found the same sites of pseudarthrosis and decided to perform parietectomy of the fifth, sixth, and seventh ribs. A Gore-Tex patch was used to bridge the gap created by the resection. In immediate postoperative care, the patient's pain was quickly and sufficiently eased by stage 1 and 2 pain killers. The results of bone samples taken from the pseudarthrosis sites all found . Five months after surgery, the patient had considerable improvement in pain sensations. Computed tomography showed healing of ribs, the plate in place, and no sign of complications.
PubMed: 37696779
DOI: 10.5090/jcs.23.041 -
Frontiers in Bioscience (Landmark... Aug 2023causes upregulation of inflammatory factors, such as cycloxygenase-2, prostaglandin E2, interleukin-1β, and tumor necrosis factor-alpha, increased levels of reactive...
BACKGROUND
causes upregulation of inflammatory factors, such as cycloxygenase-2, prostaglandin E2, interleukin-1β, and tumor necrosis factor-alpha, increased levels of reactive oxygen species (ROS) and inward flow of calcium ions. This causes increased levels of the antimicrobial peptide LL-37 and inflammation of the skin, leading to redness, swelling, itching and other symptoms. fruit oil (SCO) is rich in lignan active ingredients with various antioxidant and anti-inflammatory properties.
METHODS
In this study, SCO is obtained by supercritical CO2 fluid extraction. SCO's anti-inflammatory actions were investigated using -induced inflammation HaCaT cells model. A method based on reversed-phase high-pressure liquid chromatography with a diode array detector was developed and validated for the simultaneous detection of five lignan components. Levels of inflammatory factors and LL-37 were measured by ELISA kit and western blot respectively. Ca2+ and ROS levels detected by flow cytometry.
RESULTS
The experimental results show that the contents of schisanol A, schisanol B, schisanin A, schisanin B, and schisanin C were 33.89 ± 0.24, 14.89 ± 0.45, 8.92 ± 0.02, 29.14 ± 0.67, and 4.74 ± 0.09 mg/g, respectively. Studies have demonstrated that SCO can alleviate skin inflammation by inhibiting the COX-2/PGE2 and NF-κB signalling pathway. In addition, SCO can inhibit ROS production, significantly block inward Ca2+ flow, alleviate cell damage, and modulate the content of the antimicrobial peptide LL-37.
CONCLUSIONS
In summary, our study elucidated the anti-inflammatory activity of SCO in a cell model and provided a scientific basis for its application as a raw material in skin care.
Topics: Humans; Propionibacterium acnes; Schisandra; Calcium; Cathelicidins; Fruit; HaCaT Cells; Reactive Oxygen Species; Inflammation; Antimicrobial Peptides; Dinoprostone
PubMed: 37664918
DOI: 10.31083/j.fbl2808177 -
Frontiers in Cellular and Infection... 2023Cryptosporidiosis is a leading cause of diarrheal-associated morbidity and mortality, predominantly affecting children under 5 years old in low-and-middle-income...
INTRODUCTION
Cryptosporidiosis is a leading cause of diarrheal-associated morbidity and mortality, predominantly affecting children under 5 years old in low-and-middle-income countries. There is no effective treatment and no vaccine. New therapeutics are emerging from drug discovery efforts. It is critical that mode of action studies are performed alongside drug discovery to ensure the best clinical outcomes. Unfortunately, technology to identify and validate drug targets for is severely lacking.
METHODS
We used lysyl-tRNA synthetase (KRS) and DDD01510706 as a target-compound pair to develop both chemical and genetic tools for mode of action studies for . We adapted thermal proteome profiling (TPP) for , an unbiased approach for target identification.
RESULTS
Using TPP we identified the molecular target of DDD01510706 and confirm that it is KRS. Genetic tools confirm that KRS is expressed throughout the life cycle and that this target is essential for parasite survival. Parasites genetically modified to over-express KRS or parasites with a mutation at the compound-binding site are resistant to treatment with DDD01510706. We leveraged these mutations to generate a second drug selection marker for genetic modification of , KRS. This second selection marker is interchangeable with the original selection marker, Neo, and expands the range of reverse genetic approaches available to study parasite biology. Due to the sexual nature of the life cycle, parental strains containing different drug selection markers can be crossed .
DISCUSSION
Selection with both drug markers produces highly efficient genetic crosses (>99% hybrid progeny), paving the way for forward genetics approaches in .
Topics: Child; Humans; Child, Preschool; Cryptosporidium; Cryptosporidiosis; Lysine-tRNA Ligase; Binding Sites; Diarrhea; Propionibacterium acnes
PubMed: 37600947
DOI: 10.3389/fcimb.2023.1236814