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MSphere Mar 2021, one of the largest bacterial phyla, are ubiquitous in many of Earth's ecosystems and often act as defensive symbionts with animal hosts. Members of the phylum have...
, one of the largest bacterial phyla, are ubiquitous in many of Earth's ecosystems and often act as defensive symbionts with animal hosts. Members of the phylum have repeatedly been isolated from basidiomycete-cultivating fungus-farming termites that maintain a monoculture fungus crop on macerated dead plant substrate. The proclivity for antimicrobial and enzyme production of make them likely contributors to plant decomposition and defense in the symbiosis. To test this, we analyzed the prophylactic (biosynthetic gene cluster [BGC]) and metabolic (carbohydrate-active enzyme [CAZy]) potential in 16 (10 existing and six new genomes) termite-associated and compared these to the soil-dwelling close relatives. Using antiSMASH, we identified 435 BGCs, of which 329 (65 unique) were similar to known compound gene clusters, while 106 were putatively novel, suggesting ample prospects for novel compound discovery. BGCs were identified among all major compound categories, including 26 encoding the production of known antimicrobial compounds, which ranged in activity (antibacterial being most prevalent) and modes of action that might suggest broad defensive potential. Peptide pattern recognition analysis revealed 823 (43 unique) CAZymes coding for enzymes that target key plant and fungal cell wall components (predominantly chitin, cellulose, and hemicellulose), confirming a substantial degradative potential of these bacteria. Comparison of termite-associated and soil-dwelling bacteria indicated no significant difference in either BGC or CAZy potential, suggesting that the farming termite hosts may have coopted these soil-dwelling bacteria due to their metabolic potential but that they have not been subject to genome change associated with symbiosis. have repeatedly been isolated in fungus-farming termites, and our genome analyses provide insights into the potential roles they may serve in defense and for plant biomass breakdown. These insights, combined with their relatively higher abundances in fungus combs than in termite gut, suggest that they are more likely to play roles in fungus combs than in termite guts. Up to 25% of the BGCs we identify have no similarity to known clusters, indicating a large potential for novel chemistry to be discovered. Similarities in metabolic potential of soil-dwelling and termite-associated bacteria suggest that they have environmental origins, but their consistent presence with the termite system suggests their importance for the symbiosis.
Topics: Actinobacteria; Animals; Fungi; Genome, Bacterial; Genomics; Isoptera; Multigene Family; Phylogeny; Symbiosis
PubMed: 33658277
DOI: 10.1128/mSphere.01233-20 -
Infection and Drug Resistance 2023was first isolated in 2012 in Gelibolu, Canakkale, Turkey, and has not been reported to be isolated from humans until now. We have isolated it from the bronchoalveolar...
BACKGROUND
was first isolated in 2012 in Gelibolu, Canakkale, Turkey, and has not been reported to be isolated from humans until now. We have isolated it from the bronchoalveolar lavage fluid (BLF) of a patient with pneumonia and found its drug resistance. It is the first time that has been isolated from humans since its discovery and naming. This case may provide new ideas and methods for the clinical diagnosis and treatment of pulmonary actinomycosis.
CASE DESCRIPTION
The patient was a 75-year-old male who was hospitalized in a township hospital and failed to improve after penicillin treatment. After admission to our hospital, the patient was treated with piperacillin/tazobactam according to clinical guidelines for 14 days. was isolated from the patient's BLF and was identified by 16S rRNA sequencing. This report shows the biological characteristics and in vitro drug susceptibility testing, as well as the genomics analysis based on next-generation sequencing (NGS). The results demonstrated that was easy to be mistakenly identified as dental caries by using the Merieux ANC identification card. Based on the MIC test, was susceptible to tetracyclines, quinolones and sulfonamides, but resistant to carbapenems, penicillins and cephalosporins. The K-B test results showed was highly sensitive to piperacillin/tazobactam. Genomic analysis based on NGS showed that the belongs to EF-Tu mutants conferring resistance to inhibitor , and .
CONCLUSION
is generally sensitive to Penicillin but is not. In vitro drug susceptibility test is needed to support individualized drug use to avoid delay in the disease.
PubMed: 37228659
DOI: 10.2147/IDR.S409701 -
Journal of Natural Products Jul 2015Actinomadura melliaura ATCC 39691, a strain isolated from a soil sample collected in Bristol Cove, California, is a known producer of the disaccharide-substituted AT2433...
Actinomadura melliaura ATCC 39691, a strain isolated from a soil sample collected in Bristol Cove, California, is a known producer of the disaccharide-substituted AT2433 indolocarbazoles (6-9). Reinvestigation of this strain using new media conditions led to >40-fold improvement in the production of previously reported AT2433 metabolites and the isolation and structure elucidation of the four new analogues, AT2433-A3, A4, A5, and B3 (1-4). The availability of this broader set of compounds enabled a subsequent small antibacterial/fungal/cancer SAR study that revealed disaccharyl substitution, N-6 methylation, and C-11 chlorination as key modulators of bioactivity. The slightly improved anticancer potency of the newly reported N-6-desmethyl 1 (compared to 6) contrasts extensive SAR of monoglycosylated rebeccamycin-type topoisomerase I inhibitors where N-6 alkylation has contributed to improved potency and ADME. Complete 2D NMR assignments for the known metabolite BMY-41219 (5) and (13)C NMR spectroscopic data for the known analogue AT2433-B1 (7) are also provided for the first time.
Topics: Actinomycetales; Antibiotics, Antineoplastic; California; Carbazoles; Humans; Indole Alkaloids; Microbial Sensitivity Tests; Micrococcus luteus; Molecular Structure; Mycobacterium smegmatis; Nuclear Magnetic Resonance, Biomolecular; Saccharomyces cerevisiae; Soil Microbiology; Staphylococcus aureus; Topoisomerase I Inhibitors
PubMed: 26091285
DOI: 10.1021/acs.jnatprod.5b00429 -
Protein Science : a Publication of the... Dec 2016Kijanimicin is an antitumor antibiotic isolated from Actinomadura kijaniata. It is composed of three distinct moieties: a pentacyclic core, a monosaccharide referred to...
Kijanimicin is an antitumor antibiotic isolated from Actinomadura kijaniata. It is composed of three distinct moieties: a pentacyclic core, a monosaccharide referred to as d-kijanose, and a tetrasaccharide chain composed of l-digitoxose units. d-Kijanose is a highly unusual nitro-containing tetradeoxysugar, which requires at least ten enzymes for its production. Here we describe a structural analysis of one of these enzymes, namely KijD1, which functions as a C-3'-methyltransferase using S-adenosylmethionine as its cofactor. For this investigation, two ternary complexes of KijD1, determined in the presence of S-adenosylhomocysteine (SAH) and dTDP or SAH and dTDP-3-amino-2,3,6-trideoxy-4-keto-3-methyl-d-glucose, were solved to 1.7 or 1.6 Å resolution, respectively. Unexpectedly, these structures, as well as additional biochemical analyses, demonstrated that the quaternary structure of KijD1 is a dimer. Indeed, this is in sharp contrast to that previously observed for the sugar C-3'-methyltransferase isolated from Micromonospora chalcea. By the judicious use of site-directed mutagenesis, it was possible to convert the dimeric form of KijD1 into a monomeric version. The quaternary structure of KijD1 could not have been deduced based solely on bioinformatics approaches, and thus this investigation highlights the continuing need for experimental validation.
Topics: Actinobacteria; Aminoglycosides; Bacterial Proteins; Methyltransferases; Protein Domains; Protein Structure, Quaternary
PubMed: 27595766
DOI: 10.1002/pro.3034 -
PloS One 2020Mycetoma is a chronic, granulomatous infection of subcutaneous tissue, that may involve deep structures and bone. It can be caused by bacteria (actinomycetoma) or fungi...
BACKGROUND
Mycetoma is a chronic, granulomatous infection of subcutaneous tissue, that may involve deep structures and bone. It can be caused by bacteria (actinomycetoma) or fungi (eumycetoma). There is an epidemiological association between mycetoma and the environment, including rainfall, temperature and humidity but there are still many knowledge gaps in the identification of the natural habitat of actinomycetes, their primary reservoir, and their precise geographical distribution. Knowing the potential distribution of this infection and its ecological niche in endemic areas is relevant to determine disease management strategies and etiological agent habitat or reservoirs.
METHODOLOGY/PRINCIPAL FINDINGS
This was an ambispective descriptive study of 31 patients with actinomycetoma. We determined the biophysical characteristics including temperature, precipitation, soil type, vegetation, etiological agents, and mapped actinomycetoma cases in Northeast Mexico. We identified two disease cluster areas. One in Nuevo Leon, with a predominantly kastanozems soil type, with a mean annual temperature of 22°, and a mean annual precipitation of 585.2 mm. Herein, mycetoma cases were produced by Actinomadura pelletieri, Actinomadura madurae, Nocardia brasiliensis, and Nocardia spp. The second cluster was in San Luis Potosí, where lithosols soil type predominates, with a mean annual temperature of 23.5° and a mean annual precipitation of 635.4 mm. In this area, all the cases were caused by N. brasiliensis. A. madurae cases were identified in rendzinas, kastanozems, vertisols, and lithosols soils, and A. pelletieri cases in xerosols, kastanozems, and rendzinas soils. Previous thorn trauma with Acacia or Prosopis plants was referred by 35.4% of subjects. In these states, the presence of thorny plants, such as Acacia spp., Prosopis spp., Senegalia greggi, Vachellia farnesiana and Vachellia rigidula, are common.
CONCLUSIONS/SIGNIFICANCE
Mapping this neglected tropical infection aids in the detection of disease cluster areas, the development of public health strategies for early diagnosis and disease prediction models; this paves the way for more ecological niche etiological agent research.
Topics: Adolescent; Adult; Aged; Climate; Cross-Sectional Studies; Female; Geography, Medical; Humans; Male; Mexico; Middle Aged; Mycetoma; Soft Tissue Infections; Soil; Young Adult
PubMed: 32384126
DOI: 10.1371/journal.pone.0232556 -
PloS One 2020The type I polyketide SF2487/A80577 (herein referred to as tetromadurin) is a polyether tetronate ionophore antibiotic produced by the terrestrial Gram-positive...
The type I polyketide SF2487/A80577 (herein referred to as tetromadurin) is a polyether tetronate ionophore antibiotic produced by the terrestrial Gram-positive bacterium Actinomadura verrucosospora. Tetromadurin is closely related to the polyether tetronates tetronasin (M139603) and tetronomycin, all of which are characterised by containing a tetronate, cyclohexane, tetrahydropyran, and at least one tetrahydrofuran ring. We have sequenced the genome of Actinomadura verrucosospora to identify the biosynthetic gene cluster responsible for tetromadurin biosynthesis (the mad gene cluster). Based on bioinformatic analysis of the 32 genes present within the cluster a plausible biosynthetic pathway for tetromadurin biosynthesis is proposed. Functional confirmation of the mad gene cluster is obtained by performing in-frame deletions in each of the genes mad10 and mad31, which encode putative cyclase enzymes responsible for cyclohexane and tetrahydropyran formation, respectively. Furthermore, the A. verrucosospora Δmad10 mutant produces a novel tetromadurin metabolite that according to mass spectrometry analysis is analogous to the recently characterised partially cyclised tetronasin intermediate lacking its cyclohexane and tetrahydropyran rings. Our results therefore elucidate the biosynthetic machinery of tetromadurin biosynthesis and lend support for a conserved mechanism of cyclohexane and tetrahydropyran biosynthesis across polyether tetronates.
Topics: Actinobacteria; Actinomadura; Amino Acid Sequence; Anti-Bacterial Agents; Base Sequence; Biosynthetic Pathways; Cloning, Molecular; Ethers; Furans; Macrolides; Multigene Family; Polyketide Synthases; Polyketides; Sequence Alignment
PubMed: 32925967
DOI: 10.1371/journal.pone.0239054 -
Molecules (Basel, Switzerland) Jun 2021Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and...
Redox-active drugs are the mainstay of parasite chemotherapy. To assess their repurposing potential for eumycetoma, we have tested a set of nitroheterocycles and peroxides in vitro against two isolates of , the main causative agent of eumycetoma in Sudan. All the tested compounds were inactive except for niclosamide, which had minimal inhibitory concentrations of around 1 µg/mL. Further tests with niclosamide and niclosamide ethanolamine demonstrated in vitro activity not only against but also against spp., causative agents of actinomycetoma, with minimal inhibitory concentrations below 1 µg/mL. The experimental compound MMV665807, a related salicylanilide without a nitro group, was as active as niclosamide, indicating that the antimycetomal action of niclosamide is independent of its redox chemistry (which is in agreement with the complete lack of activity in all other nitroheterocyclic drugs tested). Based on these results, we propose to further evaluate the salicylanilides, niclosamidein particular, as drug repurposing candidates for mycetoma.
Topics: Actinomadura; Animals; Humans; Madurella; Mycetoma; Niclosamide
PubMed: 34209118
DOI: 10.3390/molecules26134005 -
Applied Microbiology Jul 1969Thirteen red strains of Actinomadura (Nocardia) pelletieri and three of A. madurae were shown to produce prodigiosin-like pigments. Both of the two major pigments which...
Thirteen red strains of Actinomadura (Nocardia) pelletieri and three of A. madurae were shown to produce prodigiosin-like pigments. Both of the two major pigments which were observed on thin-layer chromatograms had R(F) values significantly greater than prodigiosin. The main pigment from A. madurae 953 was shown by mass and nuclear magnetic resonance spectroscopies to be nonylprodigiosin. The major pigment from A. pellitieri had a C(11)H(22) side chain in a ring form, but it was distinctly different from metacycloprodigiosin. "Prodiginine" was proposed as a name for the invariant aromatic portion of the prodigiosin structure.
Topics: Anti-Bacterial Agents; Chromatography; Chromatography, Thin Layer; Magnetic Resonance Spectroscopy; Nocardia; Pigments, Biological; Prodigiosin; Pyrroles; Spectrum Analysis
PubMed: 5803627
DOI: 10.1128/am.18.1.1-3.1969 -
Frontiers in Microbiology 2020Plant associated endophytic actinobacteria may contribute to plant growth and defense by direct or indirect methods. Our aim was to evaluate the plant growth promoting...
Plant associated endophytic actinobacteria may contribute to plant growth and defense by direct or indirect methods. Our aim was to evaluate the plant growth promoting and antifungal activities of endophytic actinobacteria associated with spp. and related genera, to find potent plant growth promoting strains that could be applied in future microbe based bioformulations. We isolated 46 endophytic actinobacteria based on morphological characteristics of the isolates. 16S rRNA gene sequence analysis showed that the strains represented nine actinobacterial genera, and . functional characterization of the isolates for plant growth promoting (PGP) traits revealed many potent PGP isolates such as, SA1 and S43 which showed all the tested PGP traits, i.e., phosphate solubilization, indole-3-acetic acid (IAA), ammonia, siderophore and chitinase production. Out of the 46 endophytic actinobacteria isolates, 21 showed inhibition against atleast one test fungal phytopathogen and, isolates SA25 and SA29 exhibited broad spectrum antifungal activity against all the tested phytopathogens. Most of the endophytic actinobacteria isolates having antifungal activity were positive for the presence of chitinase, NRPS (Non-ribosomal peptides synthetase) or PKS-1 (Polyketide Synthase) gene, suggesting the presence of distinctive mechanisms to inhibit the growth of pathogenic plant fungi. ARDRA (Amplified Ribosomal DNA Restriction analysis) and BOX-PCR fingerprinting analysis of the potent isolates with antagonistic activity grouped the isolates into 5 and 4 separate clusters, respectively. In addition, an assessment using bonitur scale revealed the top ranked isolates based on their PGP and biocontrol traits. Further detection of IAA production by the top ranked actinobacterial isolates namely, SA1, T1LA3 and S85 by using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) was done. Endophytic actinobacteria isolates, namely, SA1, T1LA3, and SA14 were further tested for their efficacy in promoting the growth of commercial tea clones, namely, TV1, TV9, TV18, and TV22 in nursery conditions. All the endophytic isolates tested showed significant differences ( ≤ 0.05) in terms of plant growth promoting parameters in the treated plants compared to untreated control and may, thus be, deemed as potential candidates for application in bioformulations for tea growth.
PubMed: 32180767
DOI: 10.3389/fmicb.2020.00318 -
Asian Pacific Journal of Tropical... Oct 2016To evaluate the ability of Actinomadura madurae (A. madurae) and Nocardia asteroides (N. asteroides), using Candida albicans (C. albicans) as prototypic control, to...
OBJECTIVE
To evaluate the ability of Actinomadura madurae (A. madurae) and Nocardia asteroides (N. asteroides), using Candida albicans (C. albicans) as prototypic control, to elicit the activation and IL-1β secretion of blood phagocytic cells from healthy donors.
METHODS
Microscopic evaluation of phagocytosis/activation, cell viability and spectrophotometric quantitation of endocytosis/activation, were assessed by using formazan blue test in human blood phagocytes infected with C. albicans, A. madurae or N. asteroides treated with either normal human serum (NHS) or with decomplemented NHS. Interlukin-1β from culture supernatants of infected polymorphonuclear was tested by ELISA kit assay.
RESULTS
Microscopic assay showed that phagocytosis and activation of adherent mononuclear phagocytes were greater with C. albicans followed by A. madurae and then by N. asteroides. Spectrophotometric assay in polymorphonuclear phagocytes infected with NHS-treated pathogens indicated that activation was similarly higher by C. albicans and A. madurae and lower by N. asteroides. Kinetic assays in infected polymorphonuclear cells showed that viability was decreased by C. albicans and N. asteroides or unaffected with A. madurae. Levels of IL-1β at 8 h of incubation were higher with C. albicans followed by A. madurae whereas lower levels were found with N. asteroides.
CONCLUSIONS
The extent of cell-viability and activation as well IL-1β secretion may be related with the virulence of C. albicans and N. asteroides and other parameters remain to be explored for assessing the virulence of A. madurae.
PubMed: 27794389
DOI: 10.1016/j.apjtm.2016.07.026