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Current Opinion in Microbiology Dec 2023Throughout the golden age of antibiotic discovery, Streptomyces have been unsurpassed for their ability to produce bioactive metabolites. Yet, this success has been... (Review)
Review
Throughout the golden age of antibiotic discovery, Streptomyces have been unsurpassed for their ability to produce bioactive metabolites. Yet, this success has been hampered by rediscovery. As we enter a new stage of biodiscovery, omics data and existing scientific repositories can enable informed choices on the biodiversity that may yield novel antibiotics. Here, we focus on the chemical potential of rare actinomycetes, defined as bacteria within the order Actinomycetales, but not belonging to the genus Streptomyces. They are named as such due to their less-frequent isolation under standard laboratory practices, yet there is increasing evidence to suggest these biologically diverse genera harbour considerable biosynthetic and chemical diversity. In this review, we focus on examples of successful isolation and genera that have been the focus of more concentrated biodiscovery efforts, we survey the representation of rare actinomycete taxa, compared with Streptomyces, across natural product data repositories in addition to its biosynthetic potential. This is followed by an overview of clinically useful drugs produced by rare actinomycetes and considerations for future biodiscovery efforts. There is much to learn about these underexplored taxa, and mounting evidence suggests that they are a fruitful avenue for the discovery of novel antimicrobials.
Topics: Actinobacteria; Actinomyces; Anti-Bacterial Agents; Streptomyces; Biodiversity
PubMed: 37804816
DOI: 10.1016/j.mib.2023.102385 -
Frontiers in Microbiology 2024Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide, with its etiology attributed to a complex interplay of genetic, dietary, environmental...
BACKGROUND
Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide, with its etiology attributed to a complex interplay of genetic, dietary, environmental factors, and infections such as . Despite the known risk factors, the role of gut microbiota in the development of gastric cancer remains insufficiently explored. This study aims to elucidate the causal relationship between gut microbiota and gastric cancer using a two-sample Mendelian Randomization (MR) approach.
METHODS
Utilizing genome-wide association study (GWAS) summary data from the MiBioGen consortium and gastric cancer datasets, we selected instrumental variables for MR analysis based on their association with specific microbiota. We employed several MR methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and others, to estimate the causal effects of gut microbiota diversity on the risk of developing gastric cancer.
RESULTS
Our analysis identified significant associations between certain gut microbiota and gastric cancer risk. Specifically, taxa such as (OR = 0.540, 95%CI: 0.354-0.823, = 0.004), (OR = 0.756, 95%CI: 0.613-0.932, = 0.009), (OR = 0.816, 95%CI: 0.666-1.000, < 0.05), (OR = 0.816, 95%CI: 0.666-1.000, < 0.05), (OR = 0.863, 95%CI: 0.746-0.999, = 0.048) were found to have a protective effect against gastric cancer. Conversely, an increased risk of gastric cancer was associated with the abundance of (OR = 1.342, 95%CI: 1.071-1.681, = 0.011), (OR = 1.132, 95%CI: 1.012-1.267, = 0.030), and (OR = 1.207, 95%CI: 1.074-1.355, = 0.002). The findings were robust across various MR methods and were not driven by any single SNP, indicating a genuine causal relationship.
CONCLUSION
Our studies have shown that there is a causal relationship between intestinal flora and gastric cancer at the genetic level. , , , , , and as having a protective role against GC, while , , and were associated with an increased risk.
PubMed: 38628871
DOI: 10.3389/fmicb.2024.1383530 -
Molecules (Basel, Switzerland) Apr 2023α-Glucosidase (AGS) inhibitors have been regarded as an ideal target for the management of type 2 diabetes mellitus (T2DM) since they can maintain an acceptable blood...
α-Glucosidase (AGS) inhibitors have been regarded as an ideal target for the management of type 2 diabetes mellitus (T2DM) since they can maintain an acceptable blood glucose level by delaying the digestion of carbohydrates and diminishing the absorption of monosaccharides. In the process of our endeavor in mining AGS inhibitors from natural sources, the culture broth of two mangrove-derived actinomycetes sp. WHUA03267 and sp. WHUA03072 exhibited an apparent inhibitory activity against AGS. A subsequent chemical investigation into the two extracts furnished 28 secondary metabolites that were identified by spectroscopic methods as two previously undescribed linear polyketides -, four benzenoid ansamycins -, fourteen cyclodipeptides -, one prenylated indole derivative , two fusicoccane-type diterpenoids -, two hydroxamate siderophore -, and five others -. Among all of the isolates, and were obtained from actinomycetes for the first time, while - had never been reported to occur in a marine-derived microorganism previously. In the in vitro AGS inhibitory assay, compounds , , , , , , and exhibited potent to moderate activity with IC values ranging from 35.76 ± 0.40 to 164.5 ± 15.5 μM, as compared with acarbose (IC = 422.3 ± 8.4 μM). The AGS inhibitory activity of , , , , and was reported for the first time. In particular, autolytimycin () represented the first ansamycin derivative reported to possess the AGS inhibitory activity. Kinetics analysis and molecular docking were performed to determine the inhibition types and binding modes of these inhibitors, respectively. In the MTT assay, , , , , , , and exhibited no apparent cytotoxicity to the human normal hepatocyte (LO2) cells, suggesting satisfactory safety of these AGS inhibitors.
Topics: Humans; Glycoside Hydrolase Inhibitors; Actinobacteria; Diabetes Mellitus, Type 2; Actinomyces; Molecular Docking Simulation; Streptomyces; alpha-Glucosidases; Molecular Structure
PubMed: 37175232
DOI: 10.3390/molecules28093822 -
Medical Principles and Practice :... 2022Hepatic actinomycosis (HA) is a rare infection with an indolent course, atypical clinical manifestations, nonspecific laboratory and imaging findings, and challenging... (Review)
Review
Hepatic actinomycosis (HA) is a rare infection with an indolent course, atypical clinical manifestations, nonspecific laboratory and imaging findings, and challenging diagnosis. We describe a case of a 35-year-old female who developed HA 2 weeks after gastrectomy. In addition, we analyzed clinical characteristics and outcome of 157 additional cases of HA identified in a 60-year literature review. Patients with HA were predominantly male (57%) and more than one-half were between 40 and 70 years of age. The infection was cryptogenic in 80.8% of cases. Risk factors for HA were identified in 63.1% of the patients. Clinical presentation included fever (57.7%), abdominal pain (52.1%), weight loss (45.1%), anorexia (27.5%), fatigue and chills (12.7% each), and malaise (12%) over a 2.35 ± 3.5 months period. Leukocytosis, elevated alkaline phosphatase, erythrocyte sedimentation rate, and C-reactive protein were the most frequent laboratory findings. Radiologic imaging revealed that the right lobe was more frequently affected (62.5%) with a single lesion found in two-thirds of cases. Diagnosis was achieved by histopathologic examination in 70.6% of cases. Cultures yielded Actinomyces in 45 instances, with A. israelii being the most frequent species. Less than one-half of the patients were treated only with antibiotics, while the others received combined medical and surgical treatment. The median duration of antibiotic therapy was 135 days. The presence of multiple lesions or solid tumor-like lesions (without liquefaction) was significantly associated with medical therapy alone. The outcome was favorable in most cases (94%). Although rarely encountered, HA should be considered in patients with a chronic or subacute inflammatory process of the liver to promptly diagnose and treat.
Topics: Actinomyces; Actinomycosis; Adult; Anti-Bacterial Agents; Female; Humans; Liver Abscess; Male
PubMed: 35038716
DOI: 10.1159/000521990 -
Microbiology (Reading, England) Sep 2021Last year ActinoBase, a Wiki-style initiative supported by the UK Microbiology Society, published a review highlighting the research of particular interest to the... (Review)
Review
Last year ActinoBase, a Wiki-style initiative supported by the UK Microbiology Society, published a review highlighting the research of particular interest to the actinomycete community. Here, we present the second ActinoBase review showcasing selected reports published in 2020 and early 2021, integrating perspectives in the actinomycete field. Actinomycetes are well-known for their unsurpassed ability to produce specialised metabolites, of which many are used as therapeutic agents with antibacterial, antifungal, or immunosuppressive activities. Much research is carried out to understand the purpose of these metabolites in the environment, either within communities or in host interactions. Moreover, many efforts have been placed in developing computational tools to handle big data, simplify experimental design, and find new biosynthetic gene cluster prioritisation strategies. Alongside, synthetic biology has provided advances in tools to elucidate the biosynthesis of these metabolites. Additionally, there are still mysteries to be uncovered in understanding the fundamentals of filamentous actinomycetes' developmental cycle and regulation of their metabolism. This review focuses on research using integrative methodologies and approaches to understand the bigger picture of actinomycete biology, covering four research areas: ) technology and methodology; ) specialised metabolites; ) development and regulation; and ) ecology and host interactions.
Topics: Actinobacteria; Actinomyces; Anti-Bacterial Agents; Multigene Family; Synthetic Biology
PubMed: 34515628
DOI: 10.1099/mic.0.001084 -
Molecules (Basel, Switzerland) Jun 2023Marine natural products have been recognized as the most promising source of bioactive substances for drug discovery research. This review illustrates the diversity of... (Review)
Review
Marine natural products have been recognized as the most promising source of bioactive substances for drug discovery research. This review illustrates the diversity of culturable actinobacteria associated with marine algae, their bioactivity and metabolites, and approaches to their isolation and determination of their biological properties. Furthermore, actinobacteria associated with marine algae are presented as a new subject for an extensive investigation to find novel and active natural products, which make them a potentially rich and innovative source for new drug development deserving more attention and exploration.
Topics: Actinobacteria; Actinomyces; Biological Products; Drug Discovery; Bacteria
PubMed: 37446800
DOI: 10.3390/molecules28135138 -
Diagnostics (Basel, Switzerland) Mar 2024A hypothesis-forming exploratory cross-sectional assessment was conducted to assess the occurrence and relevance of Gram-positive rod-shaped bacteria like spp. and...
Preanalytical, Analytical and Postanalytical Analyses on spp. and Actinomycetaceae in Urine Samples of Patients with Suspected Urinary Tract Infection-A Hypothesis-Forming Observational Study.
A hypothesis-forming exploratory cross-sectional assessment was conducted to assess the occurrence and relevance of Gram-positive rod-shaped bacteria like spp. and Actinomycetaceae in human urine samples. In total, 1170 urine samples from 1031 inpatients with suspected urinary tract infection were assessed for culture-based growth of Gram-positive rod-shaped bacteria applying API Coryne assays, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and in-house 16S rRNA gene sequencing. Overall, 502 different bacterial colonies from 346 urine samples taken from 324 inpatients were observed. The three quantitatively most abundant genera or genus clusters were (254 isolates, 62%), / (79 isolates, 19%), and / (29 isolates, 7%). Compared to sequencing, the diagnostic accuracy of all assessed competitor assays from the diagnostic routine was <80% for differentiation on the genus level and <30% for differentiation on the species level. Prolongated incubation for 4 days compared to 2 days resulted in additional detection of 15% of the totally recorded Gram-positive rod-shaped bacteria. An approximately 5-fold increased detection rate in mid-stream urine compared to urine acquired applying alternative sampling strategies was observed. In conclusion, in the rare event of the suspected clinical relevance of such findings, confirmatory testing with invasively sampled urine should be considered due to the high contamination rate observed in mid-stream urine. Confirmatory testing by DNA-sequencing methods should be considered if an exact identification of genus or species is regarded as relevant for the individual choice of the therapeutic strategy.
PubMed: 38611658
DOI: 10.3390/diagnostics14070746 -
Trends in Microbiology Dec 2020Adhesive pili in Gram-positive bacteria represent a variety of extracellular multiprotein polymers that mediate bacterial colonization of specific host tissues and... (Review)
Review
Adhesive pili in Gram-positive bacteria represent a variety of extracellular multiprotein polymers that mediate bacterial colonization of specific host tissues and associated pathogenesis. Pili are assembled in two distinct but coupled steps, an orderly crosslinking of pilin monomers and subsequent anchoring of the polymer to peptidoglycan, catalyzed by two transpeptidase enzymes - the pilus-specific sortase and the housekeeping sortase. Here, we review this biphasic assembly mechanism based on studies of two prototypical models, the heterotrimeric pili in Corynebacterium diphtheriae and the heterodimeric pili in Actinomyces oris, highlighting some newly emerged basic paradigms. The disparate mechanisms of protein ligation mediated by the pilus-specific sortase and the spatial positioning of adhesive pili on the cell surface modulated by the housekeeping sortase are among the notable highlights.
Topics: Actinobacteria; Actinomyces; Cell Wall; Corynebacterium diphtheriae; Fimbriae Proteins; Fimbriae, Bacterial; Gram-Positive Bacteria; Humans; Peptidoglycan; Virulence
PubMed: 32499101
DOI: 10.1016/j.tim.2020.05.008 -
Orphanet Journal of Rare Diseases Apr 2021Hepatic Actinomycosis (HA) is one of the infections that causes disorders in patients when diagnosed untimely and inappropriately. (Review)
Review
BACKGROUND
Hepatic Actinomycosis (HA) is one of the infections that causes disorders in patients when diagnosed untimely and inappropriately.
METHODS
Case reports on HA in patients published between 2000 and April 2020 were gathered by carrying out a structured search through PubMed/Medline.
RESULTS
Through a survey of the Medline database, 130 studies were identified and then, 64 cases with HA were included in the final analysis. Asia had the largest share of cases with 37.5% (24 reports), followed by Europe and the Americas. Affected patients were predominantly males (64%) and the overall mortality rate was 1% with only one male patient in his 50 s dying. Nearly all patients (92%) were immunocompetent. However, in four patients, the use of immunosuppressive medication led to depression of the immune system. Most of the patients (80%) experienced complications. In terms of the complications, the most frequent ones were previous history of abdominal surgery (32%) and foreign bodies in the abdominopelvic region (20%). Actinomyces israelii was the most common pathogen isolated from patients. Abdominal pain (66%), fever (62%), weight loss (48%), night sweat, malaise, and anorexia (14%) over about 3.1 months were the most frequently reported clinical symptoms. Extension to one or more surrounding organs was evident in 18 patients (28%). Histopathologic examination confirmed infection in 67% of the patients and samples obtained from liver puncture biopsy (32%) were most frequently used in diagnosis. Surgery or puncture drainage + anti-infection was the most common method to treat patients and penicillin, Amoxicillin, Doxycycline, and ampicillin were the most frequently used drugs to control infection.
CONCLUSION
HA should be considered in patients with a subacute or chronic inflammatory process of the liver. With accurate and timely diagnosis of infection, extensive surgery can be prevented.
Topics: Actinomyces; Actinomycosis; Asia; Europe; Humans; Male
PubMed: 33931097
DOI: 10.1186/s13023-021-01821-5 -
Scientific Reports May 2022Co-culture is an efficient strategy for natural product discovery. We have used mycolic acid-containing bacteria (MACB) Tsukamurella pumonis TP-B0596 to induce secondary...
Co-culture is an efficient strategy for natural product discovery. We have used mycolic acid-containing bacteria (MACB) Tsukamurella pumonis TP-B0596 to induce secondary metabolism by actinomycetes and have found several natural products. We also observed that MACB attached to the mycelium of Streptomyces lividans forming coaggregates during combined-culture. This stimulated interest in the interactions among actinomycetes and MACB, and we found that soil isolated cultures contained a mixture of actinomycetes and MACB. Our previously observed interactions were the result of selective screening and combination of bacteria in the lab, which warranted investigation of the existence of these interactions in the natural soil environment. Therefore, in this paper, we report the interaction between a co-isolated natural pair of actinomycetes and MACB in terms of morphology and metabolic changes. A natural pair of actinomycetes and MACB co-aggregated in liquid culture and showed metabolic changes. Interestingly, co-aggregated actinomycetes and MACB were re-isolated from soil with no obvious morphological colony differences from the colony of a single strain. The results demonstrate that there is a stochastic chance of picking colonies containing co-aggregated actinomycetes and MACB, which suggests that the pair can exist in co-aggregate form in the soil environment and interact with each other.
Topics: Actinobacteria; Actinomyces; Bacteria; Biological Products; Mycolic Acids; Soil
PubMed: 35508597
DOI: 10.1038/s41598-022-11406-2