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EMBO Molecular Medicine Feb 2022The development of eukaryote-derived antimicrobial peptides as systemically administered drugs has proven a challenging task. Here, we report the first human oral...
The development of eukaryote-derived antimicrobial peptides as systemically administered drugs has proven a challenging task. Here, we report the first human oral actinomyces-sourced defensin-actinomycesin-that shows promise for systemic therapy. Actinomycesin and its homologs are only present in actinobacteria and myxobacteria, and share similarity with a group of ancient invertebrate-type defensins reported in fungi and invertebrates. Signatures of natural selection were detected in defensins from the actinomyces colonized in human oral cavity and ruminant rumen and dental plaque, highlighting their role in adaptation to complex multispecies bacterial communities. Consistently, actinomycesin exhibited potent antibacterial activity against oral bacteria and clinical isolates of Staphylococcus and synergized with two classes of human salivary antibacterial factors. Actinomycesin specifically inhibited bacterial peptidoglycan synthesis and displayed weak immunomodulatory activity and low toxicity on human and mammalian cells and ion channels in the heart and central nervous system. Actinomycesin was highly efficient in mice infected with Streptococcus pneumoniae and mice with MRSA-induced experimental peritoneal infection. This work identifies human oral bacteria as a new source of systemic anti-infective drugs.
Topics: Actinomyces; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Defensins; Humans; Mice
PubMed: 34927385
DOI: 10.15252/emmm.202114499 -
Journal of Clinical Microbiology Feb 2023Novel bacterial taxonomy and nomenclature revisions can have significant impacts on clinical practice, disease epidemiology, and veterinary microbiology laboratory... (Review)
Review
Novel bacterial taxonomy and nomenclature revisions can have significant impacts on clinical practice, disease epidemiology, and veterinary microbiology laboratory operations. Expansion of research on the microbiota of humans, animals, and insects has significant potential impacts on the taxonomy of organisms of clinical interest. Implications of taxonomic changes may be especially important when considering zoonotic diseases. Here, we address novel taxonomy and nomenclature revisions of veterinary significance. Noteworthy discussion centers around descriptions of novel mastitis pathogens in , , and ; bovine reproductive tract pathogens in ; novel members of spp., spp., and Mycobacterium spp.; the transfer of spp. to Brucella spp.; and revisions to the genus .
Topics: Female; Animals; Cattle; Humans; Animals, Domestic; Bacteria; Zoonoses; Leptospira; Brucella
PubMed: 36533907
DOI: 10.1128/jcm.00281-22 -
Ophthalmic Plastic and Reconstructive... 2020Orbital actinomyces is a rare diagnosis with only a few cases reported in the literature. It can be difficult to diagnose due to its slow, indolent course, and...
Orbital actinomyces is a rare diagnosis with only a few cases reported in the literature. It can be difficult to diagnose due to its slow, indolent course, and nonspecific findings on imaging and clinical examination, and frequently it can masquerade as other pathologies such as neoplasm and inflammatory disease. The authors present a case of actinomyces masquerading as meningioma with findings of hyperostosis and a superior orbital roof interosseous tract on imaging.
Topics: Actinomyces; Humans; Hyperostosis; Meningeal Neoplasms; Meningioma; Orbit
PubMed: 32134768
DOI: 10.1097/IOP.0000000000001626 -
BMC Microbiology Mar 2022Actinomycetes are important microbes, and they are very important for developing active substances for useful drugs. Actinomycetes are numerous inhabitants, and they are...
BACKGROUND
Actinomycetes are important microbes, and they are very important for developing active substances for useful drugs. Actinomycetes are numerous inhabitants, and they are widely distributed in the nest of fungus-growing termites. Previously, we isolated and purified numerous actinomycetes from the combs of Odontotermes formosanus and obtained a variety of valuable natural products.
RESULTS
Here, we isolated and purified actinomycetes from fungus-growing termite Odontotermes formosanus using medium-based cultures. Among the eight media tested, M7 and I-HV media were found suitable for isolating actinomycetes. Further, 84 actinomycetes, including 79 Streptomyces isolates, were isolated and purified from O. formosanus and its combs, which belong to four genera (Streptomyces, Kribbella, Amycolatopsis, and Cellulosimicrobium). Then, the type and quantity of actinomycetes were positively correlated with the activity range of termites. Twenty-two actinomycetes strains showed antimicrobial activities. Among them, the BYF18, BYF48, BYF70, and BYF106 strains exhibited antifungal activities against five pathogenic fungi, with zone of inhibition (ZOI) values ranging from 3 to 21 mm. Grincamycin N was isolated and purified from the metabolites of Streptomyces lannensis (BYF106), and it displayed antibacterial activities against Staphylococcus aureus (ZOI = 13.82 ± 0.52 mm) and Micrococcus tetragenus (ZOI = 17.6 ± 0.5 mm) (gentamycin sulfate, as the positive control, had ZOI values of 19.9 ± 0.5 mm and 30.83 ± 0.75 mm, against S. aureus and M. tetragenus, respectively).
CONCLUSIONS
Our results confirmed that the actinomycetes associated with O. formosanus are important sources of new active substances.
Topics: Actinobacteria; Actinomyces; Actinomycetales; Animals; Antifungal Agents; Cockroaches; Fungi; Isoptera; Staphylococcus aureus
PubMed: 35337263
DOI: 10.1186/s12866-022-02501-5 -
Medicina (Kaunas, Lithuania) Oct 2021: species are part of the normal flora of humans and rarely cause disease. It is an uncommon cause of disease in humans. The clinical features of actinomycosis have...
: species are part of the normal flora of humans and rarely cause disease. It is an uncommon cause of disease in humans. The clinical features of actinomycosis have been described, and various anatomical sites (such as face, bones and joints, respiratory tract, genitourinary tract, digestive tract, central nervous system, skin, and soft tissue structures) can be affected. It is not easy to identify actinomycosis because it sometimes mimics cancer due to under-recognition. As new diagnostic methods have been applied, can now more easily be identified at the species level. Recent studies have also highlighted differences among species. We report a case of bacteremia with cutaneous actinomycosis. : A 66 years old male developed fever for a day with progressive right lower-leg erythematous swelling. Blood culture isolates yielded species, which was identified as by sequencing of the 16S rRNA gene. In addition, we searched for the term or actinomycosis cross-referenced with bacteremia or "blood culture" or "blood stream" from January 2010 to July 2020. The infectious diseases caused by species of from January 1977 to July 2020 were also reviewed. : The patient recovered well after intravenous ampicillin treatment. Poor oral hygiene was confirmed by dental examination. There were no disease relapses during the following period. Most cases of actinomycosis can be treated with penicillin. However, clinical alertness, risk factor evaluation, and identification of species can prevent inappropriate antibiotic or intervention. We also compiled a total of 18 cases of bacteremia after conducting an online database search. : In summary, we describe a case of fever and progressive cellulitis. species was isolated from blood culture, which was further identified as by 16S rRNA sequencing. The cellulitis improved after pathogen-directed antibiotics. Evaluation of risk factors in patients with bacteremia and further identification of the species are recommended for successful treatment.
Topics: Actinomyces; Actinomyces viscosus; Actinomycosis; Aged; Bacteremia; Humans; Male; RNA, Ribosomal, 16S
PubMed: 34684101
DOI: 10.3390/medicina57101064 -
Frontiers in Cellular and Infection... 2021Exploring microbial community compositions in humans with healthy versus diseased states is crucial to understand the microbe-host interplay associated with the disease...
Exploring microbial community compositions in humans with healthy versus diseased states is crucial to understand the microbe-host interplay associated with the disease progression. Although the relationship between oral cancer and microbiome was previously established, it remained controversial, and yet the ecological characteristics and their responses to oral carcinogenesis have not been well studied. Here, using the bacterial 16S rRNA gene amplicon sequencing along with the function analysis by PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2), we systematically characterized the compositions and the ecological drivers of saliva microbiome in the cohorts of orally healthy, non-recurrent oral verrucous hyperplasia (a pre-cancer lesion), and oral verrucous hyperplasia-associated oral cancer at taxonomic and function levels, and compared them with the re-analysis of publicly available datasets. Diversity analyses showed that microbiome dysbiosis in saliva was significantly linked to oral health status. As oral health deteriorated, the number of core species declined, and metabolic pathways predicted by PICRUSt2 were dysregulated. Partitioned beta-diversity revealed an extremely high species turnover but low function turnover. Functional beta-diversity in saliva microbiome shifted from turnover to nestedness during oral carcinogenesis, which was not observed at taxonomic levels. Correspondingly, the quantitative analysis of stochasticity ratios showed that drivers of microbial composition and functional gene content of saliva microbiomes were primarily governed by the stochastic processes, yet the driver of functional gene content shifted toward deterministic processes as oral cancer developed. Re-analysis of publicly accessible datasets supported not only the distinctive family taxa of and present in normal cohorts but also that and as well as the dysregulated metabolic pathways of nucleotides, amino acids, fatty acids, and cell structure were related to oral cancer. Using predicted functional profiles to elucidate the correlations to the oral health status shows superior performance than using taxonomic data among different studies. These findings advance our understanding of the oral ecosystem in relation to oral carcinogenesis and provide a new direction to the development of microbiome-based tools to study the interplay of the oral microbiome, metabolites, and host health.
Topics: Carcinogenesis; Dysbiosis; Humans; Microbiota; Phylogeny; RNA, Ribosomal, 16S
PubMed: 34604102
DOI: 10.3389/fcimb.2021.663068 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Nov 2023Cyclodipeptide (CDP) composed of two amino acids is the simplest cyclic peptide. These two amino acids form a typical diketopiperazine (DKP) ring by linking each other... (Review)
Review
Cyclodipeptide (CDP) composed of two amino acids is the simplest cyclic peptide. These two amino acids form a typical diketopiperazine (DKP) ring by linking each other with peptide bonds. This characteristic stable ring skeleton is the foundation of CDP to display extensive and excellent bioactivities, which is beneficial for CDPs' pharmaceutical research and development. The natural CDP products are well isolated from actinomycetes. These bacteria can synthesize DKP backbones with nonribosomal peptide synthetase (NRPS) or cyclodipeptide synthase (CDPS). Moreover, actinomycetes could produce a variety of CDPs through different enzymatic modification. The presence of these abundant and diversified catalysis indicates that actinomycetes are promising microbial resource for exploring CDPs. This review summarized the pathways for DKP backbones biosynthesis and their post-modification mechanism in actinomycetes. The aim of this review was to accelerate the genome mining of CDPs and their isolation, purification and structure identification, and to facilitate revealing the biosynthesis mechanism of novel CDPs as well as their synthetic biology design.
Topics: Actinobacteria; Actinomyces; Biological Products; Bacteria; Diketopiperazines; Amino Acids
PubMed: 38013180
DOI: 10.13345/j.cjb.230068 -
Probiotics and Antimicrobial Proteins Dec 2021This study evaluated the cytocompatibility and antimicrobial/antibiofilm effects of epigallocatechin-3-gallate (EGCG) associated with peptide LL-37 and its analogue...
This study evaluated the cytocompatibility and antimicrobial/antibiofilm effects of epigallocatechin-3-gallate (EGCG) associated with peptide LL-37 and its analogue KR-12-a5 against oral pathogens. The effect of the compounds on metabolism of fibroblasts was evaluated by methyltetrazolium assays. Antimicrobial activity of the compounds was evaluated on Streptococcus mutans, Enterococcus faecalis, Actinomyces israelii, and Fusobacterium nucleatum under planktonic conditions, on single- and dual-species biofilms and E. faecalis biofilms in dentinal tubules and analyzed by bacterial counts and confocal microscopy. Data were statistically analyzed considering p < 0.05. EGCG and peptide combinations were not toxic to fibroblasts. KR-12-a5 showed synergistic or addictive effects with EGCG and LL-37 against all bacteria tested. However, EGCG associated with KR-12-a5 demonstrated the highest bactericidal activity on all bacteria tested, at lower concentrations. In single-species biofilms, EGCG + KR-12-a5 eliminated S. mutans and A. israelii and reduced E. faecalis and F. nucleatum counts around 5 log CFU/mL. EGCG + KR-12-a5 reduced E. faecalis (-3.93 log CFU/mL) and eliminated S. mutans in dual-species biofilms. No growth of E. faecalis and significant reduction in A. israelii (-6.24 log CFU/mL) and F. nucleatum (-4.62 log CFU/mL) counts were detected in dual-species biofilms. The combination of EGCG and KR-12-a5 led to 88% of E. faecalis dead cells inside dentin tubules. The association of EGCG and KR-12-a5 was cytocompatible and promoted synergistic effect against biofilms of bacteria associated with endodontic infections.
Topics: Actinomyces; Anti-Infective Agents; Biofilms; Catechin; Enterococcus faecalis; Fusobacterium nucleatum; Peptides; Streptococcus mutans
PubMed: 34402021
DOI: 10.1007/s12602-021-09830-3 -
Frontiers in Cell and Developmental... 2022The development of new biomarkers for human male infertility is crucial to improve the diagnosis and the prognosis of this disease. Recently, seminal microbiota was...
The development of new biomarkers for human male infertility is crucial to improve the diagnosis and the prognosis of this disease. Recently, seminal microbiota was shown to be related to sperm quality parameters, suggesting an effect in human fertility and postulating it as a biomarker candidate. However, its relationship to sperm DNA integrity has not been studied yet. The aim of the present study is to characterize the seminal microbiota of a western Mediterranean population and to evaluate its relationship to sperm chromatin integrity parameters, and oxidative stress. For that purpose, 14 samples from sperm donors and 42 samples from infertile idiopathic patients were obtained and were analyzed to assess the composition of the microbiota through full-length gene sequencing (Illumina MiSeq platform). Microbial diversity and relative abundances were compared to classic sperm quality parameters (macroscopic semen parameters, motility, morphology and concentration), chromatin integrity (global DNA damage, double-stranded DNA breaks and DNA protamination status) and oxidative stress levels (oxidation-reduction potential). The seminal microbiota observed of these samples belonged to the phyla , , and . The most abundant genera were , , , , , , , , , and . To our knowledge, this is the first detection of genus in seminal samples. Two clusters of microbial profiles were built based on a clustering analysis, and specific genera were found with different frequencies in relation to seminal quality defects. The abundances of several bacteria negatively correlate with the sperm global DNA fragmentation, most notably , and . The latter two were also associated with higher sperm motility and additionally with lower oxidative-reduction potential. , and correlated with reduced chromatin protamination status and increased double-stranded DNA fragmentation. These effects on DNA integrity coincide in many cases with the metabolism or enzymatic activities of these genera. Significant differences between fertile and infertile men were found in the relative presence of the family and the , and genera, which supports its possible involvement in male fertility. Our findings sustain the hypothesis that the seminal microbiome has an effect on male fertility.
PubMed: 35837328
DOI: 10.3389/fcell.2022.937157 -
Marine Drugs Aug 2022Four actinomycete strains isolated from the coral and coral sand samples from the South China Sea, were found to produce a series of halogenated compounds baring...
Four actinomycete strains isolated from the coral and coral sand samples from the South China Sea, were found to produce a series of halogenated compounds baring similar ultraviolet absorption based on the analysis of HPLC and LC-MS. The production titers of halogenated compounds from SCSIO 64983 exceeded those of other similar strains leading us to focus on SCSIO 64983. Four new thiocarbazomycins A-B (-), chlocarbazomycin E (), and brocarbazomycin A (), together with three known chlocarbazomycins A-C (-) containing a carbazole core were identified, and their structures were determined using a combination of spectroscopic analysis including HRESIMS, 1D and 2D NMR. Structurally speaking, compounds and have the rare sulfur-containing carbazole nuclei, and and contain Cl and Br atoms, respectively. Although these compounds have not yet been found to have obvious biological activity, their discovery highlights the role of molecular libraries in subsequent drug discovery campaigns.
Topics: Actinobacteria; Actinomyces; Animals; Anthozoa; Carbazoles; Coral Reefs; Sand
PubMed: 36005541
DOI: 10.3390/md20080537