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Microorganisms May 2019Polyketides are a large group of secondary metabolites that have notable variety in their structure and function. Polyketides exhibit a wide range of bioactivities such... (Review)
Review
Polyketides are a large group of secondary metabolites that have notable variety in their structure and function. Polyketides exhibit a wide range of bioactivities such as antibacterial, antifungal, anticancer, antiviral, immune-suppressing, anti-cholesterol, and anti-inflammatory activity. Naturally, they are found in bacteria, fungi, plants, protists, insects, mollusks, and sponges. is a genus of Gram-positive bacteria that has a filamentous form like fungi. This genus is best known as one of the polyketides producers. Some examples of polyketides produced by are rapamycin, oleandomycin, actinorhodin, daunorubicin, and caprazamycin. Biosynthesis of polyketides involves a group of enzyme activities called polyketide synthases (PKSs). There are three types of PKSs (type I, type II, and type III) in responsible for producing polyketides. This paper focuses on the biosynthesis of polyketides in with three structurally-different types of PKSs.
PubMed: 31064143
DOI: 10.3390/microorganisms7050124 -
Frontiers in Microbiology 2022Antimicrobial resistance (AMR) is a serious threat to public health globally; it is estimated that AMR bacteria caused 1.27 million deaths in 2019, and this is set to...
Antimicrobial resistance (AMR) is a serious threat to public health globally; it is estimated that AMR bacteria caused 1.27 million deaths in 2019, and this is set to rise to 10 million deaths annually. Agricultural and soil environments act as antimicrobial resistance gene (ARG) reservoirs, operating as a link between different ecosystems and enabling the mixing and dissemination of resistance genes. Due to the close interactions between humans and agricultural environments, these AMR gene reservoirs are a major risk to both human and animal health. In this study, we aimed to identify the resistance gene reservoirs present in four microbiomes: poultry, ruminant, swine gastrointestinal (GI) tracts coupled with those from soil. This large study brings together every poultry, swine, ruminant, and soil shotgun metagenomic sequence available on the NCBI sequence read archive for the first time. We use the ResFinder database to identify acquired antimicrobial resistance genes in over 5,800 metagenomes. ARGs were diverse and widespread within the metagenomes, with 235, 101, 167, and 182 different resistance genes identified in the poultry, ruminant, swine, and soil microbiomes, respectively. The tetracycline resistance genes were the most widespread in the livestock GI microbiomes, including (W)_1, (Q)_1, (O)_1, and (44)_1. The (W)_1 resistance gene was found in 99% of livestock GI tract microbiomes, while (Q)_1 was identified in 93%, (O)_1 in 82%, and finally (44)_1 in 69%. Metatranscriptomic analysis confirmed these genes were "real" and expressed in one or more of the livestock GI tract microbiomes, with (40)_1 and (O)_1 expressed in all three livestock microbiomes. In soil, the most abundant ARG was the oleandomycin resistance gene, (B)_1. A total of 55 resistance genes were shared by the four microbiomes, with 11 ARGs actively expressed in two or more microbiomes. By using all available metagenomes we were able to mine a large number of samples and describe resistomes in 37 countries. This study provides a global insight into the diverse and abundant antimicrobial resistance gene reservoirs present in both livestock and soil microbiomes.
PubMed: 35875563
DOI: 10.3389/fmicb.2022.897905 -
Frontiers in Microbiology 2023The study aims to describe phageome of soil rhizosphere of in terms of the genes encoding CAZymes and other KEGG enzymes.
INTRODUCTION
The study aims to describe phageome of soil rhizosphere of in terms of the genes encoding CAZymes and other KEGG enzymes.
METHODS
Genes of the rhizospheric virome of the wild plant species were investigated for their ability to encode useful CAZymes and other KEGG (Kyoto Encyclopedia of Genes and Genomes) enzymes and to resist antibiotic resistance genes (ARGs) in the soil.
RESULTS
Abundance of these genes was higher in the rhizospheric microbiome than in the bulk soil. Detected viral families include the plant viral family Potyviridae as well as the tailed bacteriophages of class Caudoviricetes that are mainly associated with bacterial genera and . Viral CAZymes in this soil mainly belong to glycoside hydrolase (GH) families GH43 and GH23. Some of these CAZymes participate in a KEGG pathway with actions included debranching and degradation of hemicellulose. Other actions include biosynthesizing biopolymer of the bacterial cell wall and the layered cell wall structure of peptidoglycan. Other CAZymes promote plant physiological activities such as cell-cell recognition, embryogenesis and programmed cell death (PCD). Enzymes of other pathways help reduce the level of soil HO and participate in the biosynthesis of glycine, malate, isoprenoids, as well as isoprene that protects plant from heat stress. Other enzymes act in promoting both the permeability of bacterial peroxisome membrane and carbon fixation in plants. Some enzymes participate in a balanced supply of dNTPs, successful DNA replication and mismatch repair during bacterial cell division. They also catalyze the release of signal peptides from bacterial membrane prolipoproteins. Phages with the most highly abundant antibiotic resistance genes (ARGs) transduce species of bacterial genera , and . Abundant mechanisms of antibiotic resistance in the rhizosphere include "antibiotic efflux pump" for ARGs , and , "antibiotic target alteration" for , and "antibiotic inactivation" for .
DISCUSSION
These ARGs can act synergistically to inhibit several antibiotics including tetracycline, penam, cephalosporin, rifamycins, aminocoumarin, and oleandomycin. The study highlighted the issue of horizontal transfer of ARGs to clinical isolates and human gut microbiome.
PubMed: 37260683
DOI: 10.3389/fmicb.2023.1166148 -
Cellular and Molecular Biology... Feb 2022Despite the accelerated emerging of vaccines, development against the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) drugs discovery is still in demand....
Despite the accelerated emerging of vaccines, development against the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) drugs discovery is still in demand. Repurposing the existing drugs is an ideal time/cost-effective strategy to tackle the clinical impact of SARS CoV-2. Thereby, the present study is a promising strategy that proposes the repurposing of approved drugs against pivotal proteins that are responsible for the viral propagation of SARS-CoV-2 virus Angiotensin-converting enzyme-2 (ACE2; 2AJF), 3CL-protease: main protease (6LU7), Papain-like protease (6W9C), Receptor Binding Domain of Spike protein (6VW1), Transmembrane protease serine 2 (TMPRSS-2; 5AFW) and Furin (5MIM) by in silico methods. Molecular docking results were analyzed based on the binding energy and active site interactions accomplished with pharmacokinetic analysis. It was observed that both anisomycin and oleandomycin bind to all selected target proteins with good binding energy, achieving the most favorable interactions. Considering the results of binding affinity, pharmacokinetics and toxicity of anisomycin and oleandomycin, it is proposed that they can act as potential drugs against the SARS CoV-2 infection. Further clinical testing of the reported drugs is essential for their use in the treatment of SARS CoV-2 infection.
Topics: Anisomycin; Antiviral Agents; Drug Repositioning; Humans; Molecular Docking Simulation; Oleandomycin; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35818229
DOI: 10.14715/cmb/2021.67.5.51 -
New Zealand Veterinary Journal Nov 2016To test the non-inferiority of a novel combination intramammary product containing penicillin and cloxacillin to a reference intramammary product containing...
AIM
To test the non-inferiority of a novel combination intramammary product containing penicillin and cloxacillin to a reference intramammary product containing oxytetracycline, oleandomycin, neomycin and prednisolone with regard to bacteriological cure and clinical cure.
METHODS
Clinical cases of mastitis were sourced from 30 spring-calving dairy farms in the Southland region of New Zealand. Affected quarters were infused three times at 24 hourly intervals with either the novel combination product containing 1 g penicillin and 200 mg cloxacillin, or a reference product containing 200 mg oxytetracycline, 100 mg oleandomycin, 100 mg neomycin and 5 mg prednisolone. Cows were enrolled when a farmer detected a case of clinical mastitis. Milk samples were collected for microbiological culture immediately before treatment (Day 0) and on Days 9, 16 and 23. Bacteriological cure was compared for 187 and 178 quarters treated with the reference and novel product, respectively, and clinical cure was compared for 235 and 223 quarters, respectively. Non-inferiority was assessed by calculating the difference in cure rates between the two products and constructing a 95% CI around the difference, using the variance inflation factor to account for herd level clustering. The non-inferiority margin was 20% for both bacteriological and clinical cure. Generalising estimating equation models were used to determine predictor variables.
RESULTS
The bacteriological cure percentage, adjusted to account for herd-level clustering, was 8.5 (95% CI=-1.7-21.8)% higher for quarters treated with the novel than the reference product. The adjusted clinical cure percentage was 0.3 (95% CI=-11.2-12.0)% higher for clinical quarters treated with the novel than the reference product. Bacterial species was the only covariate for bacteriological cure (p=0.003), and quarter score at enrolment (indicating udder inflammation) was the only covariate for clinical cure (p=0.032) in the multivariable models.
CONCLUSION
The novel combination product was demonstrated to be non-inferior to the reference product with regards to both bacteriological cure and clinical cure.
CLINICAL RELEVANCE
Clinicians treating mastitis now have access to this novel combination intramammary product, and demonstration of its non-inferiority compared to the existing reference product will provide options for treatment approaches. The novel product contains fewer antimicrobials; which are of a narrower spectrum of activity.
Topics: Animals; Anti-Infective Agents; Cattle; Cloxacillin; Drug Therapy, Combination; Female; Injections; Mammary Glands, Animal; Mastitis, Bovine; Neomycin; Oleandomycin; Oxytetracycline; Penicillins; Prednisolone; Treatment Outcome
PubMed: 27430313
DOI: 10.1080/00480169.2016.1210044 -
FASEB Journal : Official Publication of... Feb 2019The regulation of cytochrome P450 activity is often achieved by structural transitions induced by substrate binding. We describe the conformational transition...
The regulation of cytochrome P450 activity is often achieved by structural transitions induced by substrate binding. We describe the conformational transition experienced upon binding by the P450 OleP, an epoxygenase involved in oleandomycin biosynthesis. OleP bound to the substrate analog 6DEB crystallized in 2 forms: one with an ensemble of open and closed conformations in the asymmetric unit and another with only the closed conformation. Characterization of OleP-6DEB binding kinetics, also using the P450 inhibitor clotrimazole, unveiled a complex binding mechanism that involves slow conformational rearrangement with the accumulation of a spectroscopically detectable intermediate where 6DEB is bound to open OleP. Data reported herein provide structural snapshots of key precatalytic steps in the OleP reaction and explain how structural rearrangements induced by substrate binding regulate activity.-Parisi, G., Montemiglio, L. C., Giuffrè, A., Macone, A., Scaglione, A., Cerutti, G., Exertier, C., Savino, C., Vallone, B. Substrate-induced conformational change in cytochrome P450 OleP.
Topics: 14-alpha Demethylase Inhibitors; Clotrimazole; Crystallography, X-Ray; Cytochrome P-450 Enzyme System; Gas Chromatography-Mass Spectrometry; Kinetics; Protein Conformation; Substrate Specificity
PubMed: 30207799
DOI: 10.1096/fj.201800450RR -
The FEBS Journal Jan 2022The translocon SecYEG and the associated ATPase SecA form the primary protein secretion system in the cytoplasmic membrane of bacteria. The secretion is essentially...
The translocon SecYEG and the associated ATPase SecA form the primary protein secretion system in the cytoplasmic membrane of bacteria. The secretion is essentially dependent on the surrounding lipids, but the mechanistic understanding of their role in SecA : SecYEG activity is sparse. Here, we reveal that the unsaturated fatty acids (UFAs) of the membrane phospholipids, including tetraoleoyl-cardiolipin, stimulate SecA : SecYEG-mediated protein translocation up to ten-fold. Biophysical analysis and molecular dynamics simulations show that UFAs increase the area per lipid and cause loose packing of lipid head groups, where the N-terminal amphipathic helix of SecA docks. While UFAs do not affect the translocon folding, they promote SecA binding to the membrane, and the effect is enhanced up to fivefold at elevated ionic strength. Tight SecA : lipid interactions convert into the augmented translocation. Our results identify the fatty acid structure as a notable factor in SecA : SecYEG activity, which may be crucial for protein secretion in bacteria, which actively change their membrane composition in response to their habitat.
Topics: Adenosine Triphosphatases; Cardiolipins; Escherichia coli; Escherichia coli Proteins; Fatty Acids, Unsaturated; Lipid Bilayers; Membrane Proteins; Oleandomycin; Phospholipids; Protein Transport; SEC Translocation Channels; SecA Proteins; Tetracycline
PubMed: 34312977
DOI: 10.1111/febs.16140 -
Saudi Journal of Biological Sciences Oct 2023The study aimed to reveal the structure and function of phageome existing in soil rhizobiome of in order to detect accidentally-packaged bacterial genes that encode...
The study aimed to reveal the structure and function of phageome existing in soil rhizobiome of in order to detect accidentally-packaged bacterial genes that encode Carbohydrate-Active enZymes (or CAZymes) and those that confer antibiotic resistance (e.g., antibiotic resistance genes or ARGs). Highly abundant genes were shown to mainly exist in members of the genera , , and . Enriched CAZymes belong to glycoside hydrolase families GH4, GH6, GH12, GH15 and GH43 and mainly function in D-glucose biosynthesis via 10 biochemical passages. Another enriched CAZyme, e.g., alpha-galactosidase, of the GH4 family is responsible for the wealth of different carbohydrate forms in rhizospheric soil sink of . ARGs of this phageome include the and genes that participate in the "antibiotic efflux pump" resistance mechanism, the mutant gene that participates in the "antibiotic target alteration" mechanism and the , , and genes that participate in the "antibiotic inactivation" mechanism. It is claimed that the genera , which harbors phages with and mutant genes, and , which harbors phages with and genes, are approaching multidrug resistance via newly disseminating phages. These ARGs inhibit many antibiotics including oleandomycin, tetracycline, rifampin and aminoglycoside. The study highlights the possibility of accidental packaging of these ARGs in soil phageome and the risk of their horizontal transfer to human gut pathogens through the food chain as detrimental impacts of soil phageome of . The study also emphasizes the beneficial impacts of phageome on soil microbiome and plant interacting in storing carbohydrates in the soil sink for use by the two entities upon carbohydrate deprivation.
PubMed: 37680975
DOI: 10.1016/j.sjbs.2023.103789 -
Food Additives & Contaminants. Part A,... Oct 2021Macrolides are critically important antimicrobials for both human and animal health and should be prioritized in risk assessments, as inappropriate use may result in...
Macrolides are critically important antimicrobials for both human and animal health and should be prioritized in risk assessments, as inappropriate use may result in antimicrobial resistance. The antimicrobials erythromycin, oleandomycin, spiramycin, tilmicosin and tylosin were analysed in infant formula samples by HPLC-MS/MS using a validated analytical method based on a modified QuEChERS extraction. The results of the occurrence study were employed to perform a dietary exposure assessment of infants to residues. In a total of 30 analysed samples, 73% contained spiramycin residues and 27%, tilmicosin residues. Calculated daily intakes ranged from 1.47 × 10 to 2.71 × 10 mg kg body weight considering all analytes, representing 0.01-0.59% of acceptable daily intakes. The results of the dietary exposure assessment were all below acceptable daily intakes, indicating low potential health concerns. However, according to Brazilian regulations, infant formulas containing residues of one or more of the investigated analytes were deemed as non-compliant.
Topics: Anti-Bacterial Agents; Brazil; Dietary Exposure; Food Contamination; Humans; Infant; Infant Formula; Macrolides
PubMed: 34254896
DOI: 10.1080/19440049.2021.1933204 -
Journal of Invertebrate Pathology Nov 2021Global high demand for Pacific white shrimp Penaeus vannamei has led to intensified cultivation and a wide range of disease problems, including bacterial diseases due to...
Global high demand for Pacific white shrimp Penaeus vannamei has led to intensified cultivation and a wide range of disease problems, including bacterial diseases due to vibrios. Three presumptive luminescent Vibrio harveyi strains (Vh5, Vh8 and Vh10) were isolated from the hepatopancreas (Vh5) and haemolymph (Vh8 and Vh10) of diseased growout Pacific white shrimp from a farm in Setiu, Terengganu, Malaysia, using Vibrio harveyi agar (VHA) differential medium. All three strains were identified as V. harveyi by biochemical characteristics. 16S rRNA gene-based phylogenetic analyses by neighbour-joining, maximum likelihood and maximum parsimony methods showed all three strains in the V. harveyi cluster. All three strains were β-haemolytic and positive for motility, biofilm formation and extracellular products (caseinase, gelatinase, lipase, DNase, amylase and chitinase). Vh10 was subjected to pathogenicity test in Pacific white shrimp by immersion challenge and determined to have a LC of 6.0 × 10 CFU mL after 168 h of exposure. Antibiotic susceptibility tests showed that all strains were resistant to oxytetracycline (OXT30), oleandomycin (OL15), amoxicillin (AML25), ampicillin (AMP10) and colistin sulphate (CT25) but sensitive to doxycycline (DO30), flumequine (UB30), oxolinic acid (OA2), chloramphenicol (C30), florfenicol (FFC30), nitrofurantoin (F5) and fosfomycin (FOS50). Each strain was also resistant to a slightly different combination of eight other antibiotics, with an overall multiple antibiotic resistance (MAR) index of 0.40, suggesting prior history of heavy exposure to the antibiotics. Vh10 infection resulted in pale or discoloured hepatopancreas, empty guts, reddening, necrosis and luminescence of uropods, as well as melanised lesions in tail muscle. Histopathological examination showed necrosis of intertubular connective tissue and tubule, sloughing of epithelial cells in hepatopancreatic tubule, haemocytic infiltration, massive vacuolation and loss of hepatopancreatic tubule structure.
Topics: Animals; Drug Resistance, Multiple, Bacterial; Penaeidae; Vibrio; Virulence
PubMed: 33878330
DOI: 10.1016/j.jip.2021.107594