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Molecules (Basel, Switzerland) Nov 2023Two previously undescribed pyrrolizine alkaloids, named phenopyrrolizins A and B ( and ), were obtained from the fermentation broth of marine-derived sp. HU138. Their...
Two previously undescribed pyrrolizine alkaloids, named phenopyrrolizins A and B ( and ), were obtained from the fermentation broth of marine-derived sp. HU138. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR spectra as well as HRESIMS data. The structure of was confirmed by single-crystal diffraction analysis and its racemization mechanism was proposed. The antifungal activity assay showed that could inhibit the mycelial growth of with the inhibitory rates of 18.9% and 35.9% at 20 μg/disc and 40 μg/disc, respectively.
Topics: Actinobacteria; Actinomyces; Micromonospora; Alkaloids; Magnetic Resonance Spectroscopy; Molecular Structure
PubMed: 38005394
DOI: 10.3390/molecules28227672 -
The Pediatric Infectious Disease Journal Jan 2024
Topics: Child; Humans; Arcanobacterium; Actinomycetales Infections; Immunocompetence
PubMed: 37922488
DOI: 10.1097/INF.0000000000004147 -
NPJ Biofilms and Microbiomes Mar 2024Colonization of the vaginal space with bacteria such as Gardnerella vaginalis and Mobiluncus mulieris is associated with increased risk for STIs, bacterial vaginosis,...
Colonization of the vaginal space with bacteria such as Gardnerella vaginalis and Mobiluncus mulieris is associated with increased risk for STIs, bacterial vaginosis, and preterm birth, while Lactobacillus crispatus is associated with optimal reproductive health. Although host-microbe interactions are hypothesized to contribute to reproductive health and disease, the bacterial mediators that are critical to this response remain unclear. Bacterial extracellular vesicles (bEVs) are proposed to participate in host-microbe communication by providing protection of bacterial cargo, delivery to intracellular targets, and ultimately induction of immune responses from the host. We evaluated the proteome of bEVs produced in vitro from G. vaginalis, M. mulieris, and L. crispatus, identifying specific proteins of immunologic interest. We found that bEVs from each bacterial species internalize within cervical and vaginal epithelial cells, and that epithelial and immune cells express a multi-cytokine response when exposed to bEVs from G. vaginalis and M. mulieris but not L. crispatus. Further, we demonstrate that the inflammatory response induced by G. vaginalis and M. mulieris bEVs is TLR2-specific. Our results provide evidence that vaginal bacteria communicate with host cells through secreted bEVs, revealing a mechanism by which bacteria lead to adverse reproductive outcomes associated with inflammation. Elucidating host-microbe interactions in the cervicovaginal space will provide further insight into the mechanisms contributing to microbiome-mediated adverse outcomes and may reveal new therapeutic targets.
Topics: Infant, Newborn; Humans; Female; Gardnerella vaginalis; Mobiluncus; Proteomics; Premature Birth; Extracellular Vesicles
PubMed: 38514622
DOI: 10.1038/s41522-024-00502-y -
Communications Biology Jan 2024Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to...
Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature's chemical repertoire.
Topics: Actinobacteria; Actinomyces; Anti-Bacterial Agents; Biological Products; Computational Biology
PubMed: 38184720
DOI: 10.1038/s42003-023-05648-7 -
Acta Crystallographica. Section D,... Nov 2023Cell-surface proteins known as adhesins enable bacteria to colonize particular environments, and in Gram-positive bacteria often contain autocatalytically formed...
Cell-surface proteins known as adhesins enable bacteria to colonize particular environments, and in Gram-positive bacteria often contain autocatalytically formed covalent intramolecular cross-links. While investigating the prevalence of such cross-links, a remarkable example was discovered in Mobiluncus mulieris, a pathogen associated with bacterial vaginosis. This organism encodes a putative adhesin of 7651 residues. Crystallography and mass spectrometry of two selected domains, and AlphaFold structure prediction of the remainder of the protein, were used to show that this adhesin belongs to the family of thioester, isopeptide and ester-bond-containing proteins (TIE proteins). It has an N-terminal domain homologous to thioester adhesion domains, followed by 51 immunoglobulin (Ig)-like domains containing ester- or isopeptide-bond cross-links. The energetic cost to the M. mulieris bacterium in retaining such a large adhesin as a single gene or protein construct suggests a critical role in pathogenicity and/or persistence.
Topics: Female; Humans; Mobiluncus; Adhesins, Bacterial; Esters
PubMed: 37860959
DOI: 10.1107/S2059798323007507 -
Medicina Clinica May 2024This study aims to assess the clinical, radiological, and histological characteristics of Actinomyces infection identified in appendectomy specimens.
OBJECTIVE
This study aims to assess the clinical, radiological, and histological characteristics of Actinomyces infection identified in appendectomy specimens.
MATERIAL AND METHODS
Between January 2013 and November 2023, 5834 patients underwent appendectomy in our clinic, and their pathology reports were retrospectively reviewed.
RESULTS
Actinomyces appendicites were reported in 14 specimens (0.23%). It was determined that appendectomy was performed in only 10 patients (71.4%), ileocecal resection was performed in two patients (14.2%) and right hemicolectomy in two patients (14.2%). The operations on five patients were performed by laparoscopy, and the operations on the other nine patients were performed by open surgery. Laparoscopy was started in three patients and converted to open surgery due to suspicion of an ileocecal mass and cecal perforation. It was found that the white blood cell count of three patients was within the normal range of reference (8-9.77mg/dL); leukocytosis was detected in other patients (10.2-18.7mg/dL). C-reactive protein was normal in one patient and high in the rest of the patients. While the first-hour erythrocyte sedimentation rate was normal in five patients, it was found to be high in the other patients. Findings on radiological imaging were reported as acute appendicitis, appendicular plastron, and ileocecal mass. As a result of the pathology findings, the patients were given oral penicillin or semi-synthetic penicillin derivatives during one month.
CONCLUSION
Ileocecal and appendecular actinomycosis are rare, and preoperative diagnosis is difficult. A definitive diagnosis is usually made after a histopathological examination. After surgery, long-term antimicrobial treatment of the patient is possible with penicillin.
Topics: Humans; Actinomycosis; Male; Female; Retrospective Studies; Middle Aged; Adult; Appendectomy; Aged; Appendicitis; Young Adult; Cecal Diseases; Laparoscopy; Actinomyces; Adolescent
PubMed: 38570296
DOI: 10.1016/j.medcli.2024.02.005 -
American Journal of Reproductive... Aug 2023Preterm birth (PTB) remains a leading cause of childhood mortality. Recent studies demonstrate that the risk of spontaneous PTB (sPTB) is increased in individuals with...
PROBLEM
Preterm birth (PTB) remains a leading cause of childhood mortality. Recent studies demonstrate that the risk of spontaneous PTB (sPTB) is increased in individuals with Lactobacillus-deficient vaginal microbial communities. One proposed mechanism is that vaginal microbes ascend through the cervix, colonize the uterus, and activate inflammatory pathways leading to sPTB. This study assessed whether intrauterine colonization with either Gardnerella vaginalis and Mobiluncus mulieris alone is sufficient to induce maternal-fetal inflammation and induce sPTB.
METHOD OF STUDY
C56/B6J mice, on embryonic day 15, received intrauterine inoculation of saline or 10 colony-forming units of G. vaginalis (n = 30), M. mulieris (n = 17), or Lactobacillus crispatus (n = 16). Dams were either monitored for maternal morbidity and sPTB or sacrificed 6 h post-infusion for analysis of bacterial growth and cytokine/chemokine expression in maternal and fetal tissues.
RESULTS
Six hours following intrauterine inoculation with G. vaginalis, M. mulieris, or L. crispatus, live bacteria were observed in both blood and amniotic fluid, and a potent immune response was identified in the uterus and maternal serum. In contrast, only a limited immune response was identified in the amniotic fluid and the fetus after intrauterine inoculation. High bacterial load (10 CFU/animal) of G. vaginalis was associated with maternal morbidity and mortality but not sPTB. Intrauterine infusion with L. crispatus or M. mulieris at 10 CFU/animal did not induce sPTB, alter pup viability, litter size, or maternal mortality.
CONCLUSIONS
Despite inducing an immune response, intrauterine infusion of live G. vaginalis or M. mulieris is not sufficient to induce sPTB in our mouse model. These results suggest that ascension of common vaginal microbes into the uterine cavity alone is not causative for sPTB.
Topics: Actinomycetales Infections; Disease Models, Animal; Gardnerella vaginalis; Mice, Inbred C57BL; Mobiluncus; Mothers; Pregnancy Complications, Infectious; Premature Birth; Vaginosis, Bacterial; Female; Animals; Mice
PubMed: 37491927
DOI: 10.1111/aji.13749 -
Journal of the American Chemical Society Aug 2023The unique bioactivities of arsenic-containing secondary metabolites have been revealed recently, but studies on arsenic secondary metabolism in microorganisms have been...
The unique bioactivities of arsenic-containing secondary metabolites have been revealed recently, but studies on arsenic secondary metabolism in microorganisms have been extremely limited. Here, we focused on the organoarsenic metabolite with an unknown chemical structure, named bisenarsan, produced by well-studied model actinomycetes and elucidated its structure by combining feeding of the putative biosynthetic precursor (2-hydroxyethyl)arsonic acid to 1326 and detailed NMR analyses. Bisenarsan is the first characterized actinomycete-derived arsenic secondary metabolite and may function as a prototoxin form of an antibacterial agent or be a detoxification product of inorganic arsenic species. We also verified the previously proposed genes responsible for bisenarsan biosynthesis, especially the (2-hydroxyethyl)arsonic acid moiety. Notably, we suggest that a C-As bond in bisenarsan is formed by the intramolecular rearrangement of a pentavalent arsenic species (arsenoenolpyruvate) by the cofactor-independent phosphoglycerate mutase homologue BsnN, that is entirely distinct from the conventional biological C-As bond formation through As-alkylation of trivalent arsenic species by -adenosylmethionine-dependent enzymes. Our findings will speed up the development of arsenic natural product biosynthesis.
Topics: Arsenic; Secondary Metabolism; Actinobacteria; Actinomyces; S-Adenosylmethionine
PubMed: 37534495
DOI: 10.1021/jacs.3c04978 -
The Lancet. Infectious Diseases Sep 2023
Topics: Humans; Actinomyces; Abdomen
PubMed: 37625860
DOI: 10.1016/S1473-3099(23)00182-2 -
Archives of Oral Biology Aug 2024The aim of this study was to investigate the difference in dental biofilm formation according to substratum direction, using an artificial biofilm model.
OBJECTIVES
The aim of this study was to investigate the difference in dental biofilm formation according to substratum direction, using an artificial biofilm model.
METHODS
A three-species biofilm, consisting of Streptococcus mutans, Streptococcus oralis, and Actinomyces naeslundii, was formed on saliva-coated hydroxyapatite (sHA) discs oriented in three directions: downward (the discs placed in the direction of gravity), vertical (the discs placed parallel to the direction of gravity), and upward (the discs placed in opposite direction of gravity). The biofilms at 22 h and 46 h of age were analyzed using microbiological and biochemical methods, fluorescence-based assays, and scanning electron microscopy to investigate difference in bacterial adhesion, early and mature biofilm formation.
RESULTS
The biofilms formed in the upward direction displayed the most complex structure, with the highest number and biovolume of bacteria, as well as the lowest pH conditions at both time points. The vertical and downward directions, however, had only scattered and small bacterial colonies. In the 22-h-old biofilms, the proportion of S. oralis was similar to, or slightly higher than, that of S. mutans in all directions of substratum surfaces. However, in the 46-h-old biofilms, S. mutans became the dominant bacteria in all directions, especially in the vertical and upward directions.
CONCLUSIONS
The direction of the substratum surface could impact the proportion of bacteria and cariogenic properties of the multi-species biofilm. Biofilms in an upward direction may exhibit a higher cariogenic potential, followed by those in the vertical and downward directions, which could be related to gravity.
Topics: Biofilms; Actinomyces; Streptococcus mutans; Microscopy, Electron, Scanning; Saliva; Streptococcus oralis; Bacterial Adhesion; Durapatite; Humans; Surface Properties; Hydrogen-Ion Concentration
PubMed: 38759390
DOI: 10.1016/j.archoralbio.2024.106002