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Communications Biology Jan 2024The nasal cavity harbors diverse microbiota that contributes to human health and respiratory diseases. However, whether and to what extent the host genome shapes the...
The nasal cavity harbors diverse microbiota that contributes to human health and respiratory diseases. However, whether and to what extent the host genome shapes the nasal microbiome remains largely unknown. Here, by dissecting the human genome and nasal metagenome data from 1401 healthy individuals, we demonstrated that the top three host genetic principal components strongly correlated with the nasal microbiota diversity and composition. The genetic association analyses identified 63 genome-wide significant loci affecting the nasal microbial taxa and functions, of which 2 loci reached study-wide significance (p < 1.7 × 10): rs73268759 within CAMK2A associated with genus Actinomyces and family Actinomycetaceae; and rs35211877 near POM121L12 with Gemella asaccharolytica. In addition to respiratory-related diseases, the associated loci are mainly implicated in cardiometabolic or neuropsychiatric diseases. Functional analysis showed the associated genes were most significantly expressed in the nasal airway epithelium tissue and enriched in the calcium signaling and hippo signaling pathway. Further observational correlation and Mendelian randomization analyses consistently suggested the causal effects of Serratia grimesii and Yokenella regensburgei on cardiometabolic biomarkers (cystine, glutamic acid, and creatine). This study suggested that the host genome plays an important role in shaping the nasal microbiome.
Topics: Humans; Genome-Wide Association Study; Nose; Microbiota; Genetic Variation; Cardiovascular Diseases
PubMed: 38291185
DOI: 10.1038/s42003-024-05822-5 -
Mikrobiyoloji Bulteni Jan 2024Actinotignum schaalii (formerly known as Actinobaculum schaalii) is an anaerobic or facultative anaerobic gram-positive bacillus that can be found commensally in the...
Actinotignum schaalii (formerly known as Actinobaculum schaalii) is an anaerobic or facultative anaerobic gram-positive bacillus that can be found commensally in the urogenital region. It can be overlooked because it grows slowly and is difficult to identify with classical microbiology laboratory techniques. Colonies become visible after 48-72 hours of incubation on blood agar in anaerobic or CO₂-rich media. While it typically causes urinary tract infection in older individuals, cases of bacteremia, vertebral osteomyelitis, endocarditis and cellulitis have been reported. Fournier's gangrene caused by A.schaalii has been reported very rarely so far. Fournier's gangrene has been defined as necrotizing fasciitis of the external genitalia, perineal and perianal region. Diabetes, immunosuppression, peripheral vascular disease, urethral anomalies, chronic alcoholism and smoking are important predisposing factors. In addition, approximately 25% of the cases have no known or identifiable etiology. The bacteria causing the infection may originate from skin, urogenital or intestinal microbiota. In this case report, a new case of Fournier's gangrene caused by A.schaalii was presented. A 65-year-old male patient admitted to the emergency department with the complaints of pain, swelling, redness in the left testis and also nausea, vomiting and chills that started three days ago. Physical examination revealed increased diameter of the scrotum, intense hyperemia of the skin and foci of necrosis. It was learned that the patient had no known chronic disease other than benign prostatic hyperplasia. The patient reported smoking of 25 packs of cigarettes per year. Routine laboratory tests revealed leukocyte= 32.41 x 109/L, neutrophil= 89.9%, procalcitonin= 1.62 ug/L, CRP= 265.07 mg/L and the patient was operated with the diagnosis of Fournier's gangrene. Gram staining of the abscess specimen obtained during the operation showed gram-positive bacilli both inside and outside the leukocytes. After 24 hours, grampositive bacilli were detected in the Gram staining of thin, transparent/gray colonies grown on 5% sheep blood and chocolate agar. The isolate was identified as A.schaalii by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) VITEK® MS (bioMérieux, France) microbial identification system. VITEK®2 ID ANC (bioMérieux, France) bacterial identification card was also used for comparison but the bacteria could be identified. As a result of the sequence analysis performed for confirmation, it was shown to be 100% homologous with Actinobaculum schaalii (GenBank accession no: FJ711193.1). For susceptibility tests, 5% sheep blood Schaedler agar was used and incubated in anaerobic environment. According to the minimal inhibitory concentration (MIC) results evaluated after 48 hours, penicillin was found to be 0.032 mg/L, clindamycin 0.125 mg/L, ciprofloxacin 0.19 mg/L, ceftazidime 4 mg/L, and amoxicillin 0.19 mg/L. The primary cause that initiated the infection in the case could not be identified, but it was thought that the presence of prostatic hyperplasia and smoking history may have contributed to the occurence or the progress of the disease. It is noteworthy that the ciprofloxacin MIC result was quite low compared to other studies. In addition, this study revealed the value of MALDI-TOF MS based methods in identification. In conclusion, it is thought that a significant proportion of A.schaalii infections may be overlooked due to the difficulty in growth and identification. Increasing the diagnostic power of clinical microbiology laboratories for poorly identified bacteria and renewing the databases of commercial identification systems are important for the early and accurate diagnosis and treatment of serious infections that may occur with such agents.
Topics: Male; Humans; Animals; Sheep; Aged; Fournier Gangrene; Agar; Actinomycetaceae; Bacteria, Anaerobic; Ciprofloxacin
PubMed: 38263943
DOI: 10.5578/mb.20249908 -
Frontiers in Microbiology 2023Enteric dysbacteriosis is strongly associated with nonalcoholic fatty liver disease (NAFLD). However, the underlying causal relationship remains unknown. Thus, the...
INTRODUCTION
Enteric dysbacteriosis is strongly associated with nonalcoholic fatty liver disease (NAFLD). However, the underlying causal relationship remains unknown. Thus, the present study aimed to investigate the relationship between gut microbiota and NAFLD using Mendelian randomization (MR) and analyze the target genes potentially regulated by specific microbiota.
METHODS
Bidirectional two-sample MR analysis was performed using inverse variance weighted (IVW) supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Data were pooled from gut microbiota and NAFLD association studies. The least absolute shrinkage, selection operator regression, and the Support Vector Machine algorithm were used to identify genes regulated by these intestinal flora in NAFLD. The liver expression of these genes was verified in methionine choline-deficient (MCD) diet-fed mice.
RESULTS
IVW results confirmed a causal relationship between eight specific gut microbes and NAFLD. Notably, the order Actinomycetales, NB1n, the family Actinomycetaceae, Oxalobacteraceae and the genus were positively correlated, whereas Lactobacillaceae, the , and were negatively correlated with NAFLD onset. In NAFLD, these eight bacteria regulated four genes: colony-stimulating factor 2 receptor β, fucosyltransferase 2, 17-beta-hydroxysteroid dehydrogenase 14, and microtubule affinity regulatory kinase 3 (). All genes, except , were differentially expressed in the liver tissues of MCD diet-fed mice.
DISCUSSION
The abundance of eight gut microbiota species and NAFLD progression displayed a causal relationship based on the expression of the four target genes. Our findings contributed to the advancement of intestinal microecology-based diagnostic technologies and targeted therapies for NAFLD.
PubMed: 38260910
DOI: 10.3389/fmicb.2023.1320279 -
BMC Infectious Diseases Jan 2024Actinomyces turicensis is rarely responsible of clinically relevant infections in human. Infection is often misdiagnosed as malignancy, tuberculosis, or nocardiosis,...
BACKGROUND
Actinomyces turicensis is rarely responsible of clinically relevant infections in human. Infection is often misdiagnosed as malignancy, tuberculosis, or nocardiosis, therefore delaying the correct identification and treatment. Here we report a case of a 55-year-old immunocompetent adult with brain abscess caused by A. turicensis. A systematic review of A. turicensis infections was performed.
METHODS
A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases MEDLINE, Embase, Web of Science, CINAHL, Clinicaltrials.gov and Canadian Agency for Drugs and Technology in Health (CADTH) were searched for all relevant literature.
RESULTS
Search identified 47 eligible records, for a total of 67 patients. A. turicensis infection was most frequently reported in the anogenital area (n = 21), causing acute bacterial skin and skin structure infections (ABSSSI) including Fournier's gangrene (n = 12), pulmonary infections (n = 8), gynecological infections (n = 6), cervicofacial district infections (n = 5), intrabdominal or breast infections (n = 8), urinary tract infections (n = 3), vertebral column infections (n = 2) central nervous system infections (n = 2), endocarditis (n = 1). Infections were mostly presenting as abscesses (n = 36), with or without concomitant bacteremia (n = 7). Fever and local signs of inflammation were present in over 60% of the cases. Treatment usually involved surgical drainage followed by antibiotic therapy (n = 51). Antimicrobial treatments most frequently included amoxicillin (+clavulanate), ampicillin/sulbactam, metronidazole or cephalosporins. Eighty-nine percent of the patients underwent a full recovery. Two fatal cases were reported.
CONCLUSIONS
To the best of our knowledge, we hereby present the first case of a brain abscess caused by A. turicensis and P. mirabilis. Brain involvement by A. turicensis is rare and may result from hematogenous spread or by dissemination of a contiguous infection. The infection might be difficult to diagnose and therefore treatment may be delayed. Nevertheless, the pathogen is often readily treatable. Diagnosis of actinomycosis is challenging and requires prompt microbiological identification. Surgical excision and drainage and antibiotic treatment usually allow for full recovery.
Topics: Adult; Humans; Middle Aged; Actinomyces; Actinomycosis; Anti-Bacterial Agents; Brain Abscess; Canada
PubMed: 38245682
DOI: 10.1186/s12879-024-08995-w -
Chemistry & Biodiversity Mar 2024In the current study, the actinomycetes associated with the red sea-derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical...
In the current study, the actinomycetes associated with the red sea-derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical diversity. Four different media, M1, ISP2, Marine Agar (MA), and Actinomycete isolation agar (AIA) were used for the isolation of three strains of actinomycetes that were identified as Streptomyces sp. UR 25, Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. LC-HRMS analysis was used to investigate the chemical diversity of the isolated actinobacteria. The LC-HRMS data were statistically processed using MetaboAnalyst 5.0 viz to differentiate the extract groups and determine the optimal growth culturing conditions. Multivariate data statistical analysis revealed that the Micromonospora sp. extract cultured on (MA) medium is the most distinctive extract in terms of chemical composition. While, the Streptomyces sp. UR 25 extracts are differ significantly from Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. Biological investigation using in vitro cytotoxic assay for actinobacteria extracts revealed the prominent potentiality of the Streptomyces sp. UR 25 cultured on oligotrophic medium against human hepatoma (HepG2), human breast adenocarcinoma (MCF-7) and human colon adenocarcinoma (CACO2) cell lines (IC =3.3, 4.2 and 6.8 μg/mL, respectively). SwissTarget Prediction speculated that among the identified compounds, 16-deethyl, indanomycin (8) could have reasonable affinity on HDM2 active site. In this respect, molecular docking study was performed for compound (8) to reveal a substantial affinity on HDM2 active site. In addition, molecular dynamics simulations were carried out at 200 ns for the most active compound (8) compared to the co-crystallized inhibitor DIZ giving deeper information regarding their thermodynamic and dynamic properties as well.
Topics: Animals; Humans; Actinobacteria; Indian Ocean; Actinomyces; Agar; Adenocarcinoma; Caco-2 Cells; Molecular Docking Simulation; Colonic Neoplasms; Anthozoa; Antineoplastic Agents; Streptomyces
PubMed: 38193652
DOI: 10.1002/cbdv.202301617 -
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 -
Yakugaku Zasshi : Journal of the... 2024The genus Nocardia comprises gram-positive bacteria, most of which are pathogenic and cause opportunistic infections of the lungs, skin, and brain in humans. Based on a...
The genus Nocardia comprises gram-positive bacteria, most of which are pathogenic and cause opportunistic infections of the lungs, skin, and brain in humans. Based on a collaboration study with the Medical Mycology Research Center, Chiba University, we focused on Nocardia actinomycetes as a new natural-product resource. First, by culturing (monoculture) Nocardia in various media, we isolated a new aminocyclitol nabscessin A from Nocardia abscessus IFM10029 and a new γ-lactone inohanalactone from Nocardia inohanaensis IFM0092. On the other hand, by imitating the state in which the genus Nocardia actinomycete infects animal cells and culturing the genus in the presence of animal cells (coculture), this genus was expected to produce new compounds through interactions with the animal cells. Using mouse macrophage-like cells (J774.1) as animal cells, a new pantothenic acid amide derivative and a cyclic peptide, nocarjamide, with Wnt signal activation activity were isolated from Nocardia tenerifensis IFM10554 strain.
Topics: Animals; Mice; Actinobacteria; Actinomyces; Biological Products; Nocardia; Phylogeny
PubMed: 38171791
DOI: 10.1248/yakushi.23-00161-3 -
Antonie Van Leeuwenhoek Jan 2024During the course of development plants form tight interactions with microorganisms inhabiting their root zone. In turn, rhizosphere bacteria, in particular members of...
During the course of development plants form tight interactions with microorganisms inhabiting their root zone. In turn, rhizosphere bacteria, in particular members of the phylum Actinomycetota, positively influence the host plant by increasing access to essential nutrients and controlling the pathogenic microorganism's population. Herein, we report the characterisation of the rhizosphere associated actinobacteria community of Phyllostachys viridiglaucescens growing in the Nikitsky Botanical Garden (Crimean Peninsula, Ukraine). The overall composition of the bacterial community was elucidated by 16S rRNA gene amplicon sequencing followed by isolation of culturable microorganisms with the focus on actinomycetes. The metagenomic approach revealed that the representatives of phylum Actinomycetota (57.1%), Pseudomonadota (20.0%), and Acidobacteriota (12.2%) were dominating in the studied microbiome with Ilumatobacter (phylum Actinomycetota) (13.1%) being the dominant genus. Furthermore, a total of 159 actinomycete isolates, belonging to eight genera of Streptomyces, Micromonospora, Nonomuraea, Arthrobacter, Actinomadura, Kribbella, Cellulosimicrobium, and Mumia, were recovered from P. viridiglaucescens rhizosphere. The isolated species were tested for antimicrobial activity. 64% of isolates were active against at least one bacterial test-culture and 7.5% against fungal test culture. In overall, the rhizosphere bacterial communities act as a great source of actinobacterial diversity with the high potential for production of new bioactive compounds.
Topics: Actinobacteria; Actinomyces; Rhizosphere; RNA, Ribosomal, 16S; Actinomycetales; Streptomyces; Poaceae; Soil Microbiology
PubMed: 38170239
DOI: 10.1007/s10482-023-01906-0 -
Environmental Science & Technology Jan 2024The coculture theory that promotes denitrification relies on effectively utilizing the resources of low-efficiency denitrification microbes. Here, the strains sp. PYX97...
The coculture theory that promotes denitrification relies on effectively utilizing the resources of low-efficiency denitrification microbes. Here, the strains sp. PYX97 and sp. TSJ96 were isolated and showed lower denitrification capacity when cultured individually. However, the coculture of strains PYX97 and TSJ96 enhanced nitrogen removal (removed 96.40% of total nitrogen) and organic carbon reduction (removed 92.13% of dissolved organic carbon) under aerobic conditions. Nitrogen balance analysis indicated that coculturing enhanced the efficiency of nitrate converted into gaseous nitrogen reaching 70.42%. Meanwhile, the coculturing promoted the cell metabolism capacity and carbon source metabolic activity. The coculture strains PYX97 and TSJ96 thrived in conditions of C/N = 10, alkalescence, and 150 rpm shaking speed. The coculturing reduced total nitrogen and COD in the raw water treatment by 83.32 and 84.21%, respectively. During this treatment, the cell metabolic activity and cell density increased in the coculture strains PYX97 and TSJ96 reactor. Moreover, the coculture strains could utilize aromatic protein and soluble microbial products during aerobic denitrification processes in raw water treatment. This study suggests that coculturing inefficient actinomycete strains could be a promising approach for treating polluted water bodies.
Topics: Denitrification; Aerobiosis; Actinobacteria; Actinomyces; Carbon; Coculture Techniques; Nitrates; Nitrogen; Nitrification
PubMed: 38102081
DOI: 10.1021/acs.est.3c05062 -
BMC Microbiology Dec 2023Malaria is a persistent illness that is still a public health issue. On the other hand, marine organisms are considered a rich source of anti‑infective drugs and other...
Malaria is a persistent illness that is still a public health issue. On the other hand, marine organisms are considered a rich source of anti‑infective drugs and other medically significant compounds. Herein, we reported the isolation of the actinomycete associated with the Red Sea sponge Callyspongia siphonella. Using "one strain many compounds" (OSMAC) approach, a suitable strain was identified and then sub-cultured in three different media (M1, ISP2 and OLIGO). The extracts were evaluated for their in-vitro antimalarial activity against Plasmodium falciparum strain and subsequently analyzed by Liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS). In addition, MetaboAnalyst 5.0 was used to statistically analyze the LC-MS data. Finally, Molecular docking was carried out for the dereplicated metabolites against lysyl-tRNA synthetase (PfKRS1). The phylogenetic study of the 16S rRNA sequence of the actinomycete isolate revealed its affiliation to Streptomyces genus. Antimalarial screening revealed that ISP2 media is the most active against Plasmodium falciparum strain. Based on LC-HR-MS based metabolomics and multivariate analyses, the static cultures of the media, ISP2 (ISP2-S) and M1 (M1-S), are the optimal media for metabolites production. OPLS-DA suggested that quinone derivatives are abundant in the extracts with the highest antimalarial activity. Fifteen compounds were identified where eight of these metabolites were correlated to the observed antimalarial activity of the active extracts. According to molecular docking experiments, saframycin Y3 and juglomycin E showed the greatest binding energy scores (-6.2 and -5.13) to lysyl-tRNA synthetase (PfKRS1), respectively. Using metabolomics and molecular docking investigation, the quinones, saframycin Y3 (5) and juglomycin E (1) were identified as promising antimalarial therapeutic candidates. Our approach can be used as a first evaluation stage in natural product drug development, facilitating the separation of chosen metabolites, particularly biologically active ones.
Topics: Animals; Antimalarials; Actinobacteria; Callyspongia; Actinomyces; Indian Ocean; Phylogeny; RNA, Ribosomal, 16S; Molecular Docking Simulation; Lysine-tRNA Ligase; Plasmodium falciparum
PubMed: 38087203
DOI: 10.1186/s12866-023-03094-3