Journal of Microbiology

Review

Metabolite-mediated mechanisms linking the urinary microbiome to bladder cancer: Thu Anh Trần, Ho Young Lee, Hae Woong Choi; J. Microbiol. 2025;63(11):e2509001. Published online November 30, 2025; DOI: https://doi.org/10.71150/jm.2509001

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Abstract PDF: Bladder cancer is the most common malignancy of the urinary tract and is a major health burden globally. Recent advances in microbiome research have revealed that the urinary tract harbors a resident microbial community, overturning the long-held belief in its sterility. Increasing evidence suggests that microbial dysbiosis and microbially derived metabolites contribute to bladder cancer carcinogenesis, progression, and therapeutic responses. Distinct microbial signatures have been observed in bladder cancer patients, with notable differences across disease stages and between primary and recurrent cases. Mechanistic studies have demonstrated that microbe-associated metabolites and toxins can drive DNA damage, chronic inflammation, extracellular matrix remodeling, and epithelial–mesenchymal transition. In addition, biofilm formation allows bacteria to evade immune responses and promotes persistent inflammation, creating a tumor-permissive niche. Beyond pathogenesis, microbial activity also influences therapeutic outcomes; for instance, some microbial pathways can inactivate frontline chemotherapy, while others generate metabolites with anti-tumor properties. Collectively, these patterns define a microbiota–metabolite–immunity axis, presenting opportunities for precision oncology. Targeting microbial pathways, profiling urinary microbiota, and harnessing beneficial metabolites offer promising advancements in biomarker discovery, prognostic refinement, and the development of novel therapeutic strategies for bladder cancer.

Protocol

A guide to genome mining and genetic manipulation of biosynthetic gene clusters in Streptomyces: Heonjun Jeong, YeonU Choe, Jiyoon Nam, Yeon Hee Ban; J. Microbiol. 2025;63(4):e2409026. Published online April 29, 2025; DOI: https://doi.org/10.71150/jm.2409026

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Streptomyces are a crucial source of bioactive secondary metabolites with significant clinical applications. Recent studies of bacterial and metagenome-assembled genomes have revealed that Streptomyces harbors a substantial number of uncharacterized silent secondary metabolite biosynthetic gene clusters (BGCs). These BGCs represent a vast diversity of biosynthetic pathways for natural product synthesis, indicating significant untapped potential for discovering new metabolites. To exploit this potential, genome mining using comprehensive strategies that leverage extensive genomic databases can be conducted. By linking BGCs to their encoded products and integrating genetic manipulation techniques, researchers can greatly enhance the identification of new secondary metabolites with therapeutic relevance. In this context, we present a step-by-step guide for using the antiSMASH pipeline to identify secondary metabolite-coding BGCs within the complete genome of a novel Streptomyces strain. This protocol also outlines gene manipulation methods that can be applied to Streptomyces to activate cryptic clusters of interest and validate the functions of biosynthetic genes. By following these guidelines, researchers can pave the way for discovering and characterizing valuable natural products.

Citations

Citations to this article as recorded by

A review of geomicrobial bioprospecting strategies for novel therapeutic discovery from Earth’s extreme environments
Trideep Saikia, Sandipan Das
Discover Geoscience.2025;[Epub] CrossRef
Biodiversity-Driven Natural Products and Bioactive Metabolites
Giancarlo Angeles Flores, Gaia Cusumano, Roberto Venanzoni, Paola Angelini
Plants.2025; 15(1): 104. CrossRef

Journal Articles

Non-mitochondrial aconitase regulates the expression of iron-uptake genes by controlling the RNA turnover process in fission yeast: Soo-Yeon Cho , Soo-Jin Jung , Kyoung-Dong Kim , Jung-Hye Roe; J. Microbiol. 2021;59(12):1075-1082. Published online October 26, 2021; DOI: https://doi.org/10.1007/s12275-021-1438-4

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Abstract PDF

Aconitase, a highly conserved protein across all domains of life, functions in converting citrate to isocitrate in the tricarboxylic acid cycle. Cytosolic aconitase is also known to act as an iron regulatory protein in mammals, binding to the RNA hairpin structures known as iron-responsive elements within the untranslated regions of specific RNAs. Aconitase-2 (Aco2) in fission yeast is a fusion protein consisting of an aconitase and a mitochondrial ribosomal protein, bL21, residing not only in mitochondria but also in cytosol and the nucleus. To investigate the role of Aco2 in the nucleus and cytoplasm of fission yeast, we analyzed the transcriptome of aco2ΔN mutant that is deleted of nuclear localization signal (NLS). RNA sequencing revealed that the aco2ΔN mutation caused increase in mRNAs encoding iron uptake transporters, such as Str1, Str3, and Shu1. The half-lives of mRNAs for these genes were found to be significantly longer in the aco2ΔN mutant than the wild-type strain, suggesting the role of Aco2 in mRNA turnover. The three conserved cysteines required for the catalytic activity of aconitase were not necessary for this role. The UV cross-linking RNA immunoprecipitation analysis revealed that Aco2 directly bound to the mRNAs of iron uptake transporters. Aco2-mediated degradation of iron-uptake mRNAs appears to utilize exoribonuclease pathway that involves Rrp6 as evidenced by genetic interactions. These results reveal a novel role of non-mitochondrial aconitase protein in the mRNA turnover in fission yeast to fine-tune iron homeostasis, independent of regulation by transcriptional repressor Fep1.

Citations

Citations to this article as recorded by

Iron-mediated post-transcriptional regulation in Toxoplasma gondii
Megan A. Sloan, Adam Scott, Dana Aghabi, Lucia Mrvova, Clare R. Harding, Dominique Soldati-Favre
PLOS Pathogens.2025; 21(2): e1012857. CrossRef
The Key Enzymes of Carbon Metabolism and the Glutathione Antioxidant System Protect Yarrowia lipolytica Yeast Against pH-Induced Stress
Tatyana I. Rakhmanova, Natalia N. Gessler, Elena P. Isakova, Olga I. Klein, Yulia I. Deryabina, Tatyana N. Popova
Journal of Fungi.2024; 10(11): 747. CrossRef
The intricate link between iron, mitochondria and azoles in Candida species
Wouter Van Genechten, Rudy Vergauwen, Patrick Van Dijck
The FEBS Journal.2024; 291(16): 3568. CrossRef
Non-Mitochondrial Aconitase-2 Mediates the Transcription of Nuclear-Encoded Electron Transport Chain Genes in Fission Yeast
Ho-Jung Kim, Soo-Yeon Cho, Soo-Jin Jung, Yong-Jun Cho, Jung-Hye Roe, Kyoung-Dong Kim
Journal of Microbiology.2024; 62(8): 639. CrossRef
Kinetic and Regulatory Properties of Yarrowia lipolytica Aconitate Hydratase as a Model-Indicator of Cell Redox State under pH Stress
Tatyana I. Rakhmanova, Varvara Yu. Sekova, Natalya N. Gessler, Elena P. Isakova, Yulia I. Deryabina, Tatyana N. Popova, Yevgeniya I. Shurubor, Boris F. Krasnikov
International Journal of Molecular Sciences.2023; 24(8): 7670. CrossRef

Proteome analysis reveals global response to deletion of mrflbA in Monascus ruber: Qingqing Yan , Zhouwei Zhang , Yishan Yang , Fusheng Chen , Yanchun Shao; J. Microbiol. 2018;56(4):255-263. Published online February 28, 2018; DOI: https://doi.org/10.1007/s12275-018-7425-8

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Abstract PDF

Monascus spp. are commonly used for a wide variety of applications in the food and pharmaceutical industries. In previous studies, the knock-out of mrflbA (a putative regulator of the G protein α subunit) in M. ruber led to autolysis of the mycelia, decreased pigmentation and lowered mycotoxin production. Therefore, we aimed to obtain a comprehensive overview of the underlying mechanism of mrflbA deletion at the proteome level. A two-dimensional gel electrophoresis analysis of mycelial proteins indicated that the abundance of 178 proteins was altered in the ΔmrflbA strain, 33 of which were identified with high confidence. The identified proteins are involved in a range of activities, including carbohydrate and amino acid metabolism, hyphal development and the oxidative stress response, protein modification, and the regulation of cell signaling. Consistent with these findings, the activity of antioxidative enzymes and chitinase was elevated in the supernatant of the ΔmrflbA strain. Furthermore, deletion of mrflbA resulted in the transcriptional reduction of secondary metabolites (pigment and mycotoxin). In short, the mutant phenotypes induced by the deletion of mrflbA were consistent with changes in the expression levels of associated proteins, providing direct evidence of the regulatory functions mediated by mrflbA in M. ruber.

Citations

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Histone deacetylase MrHos3 negatively regulates the production of citrinin and pigments in Monascus ruber
Qianrui Liu, Yunfan Zheng, Baixue Liu, Fufang Tang, Yanchun Shao
Journal of Basic Microbiology.2023; 63(10): 1128. CrossRef
Histone deacetylase MrRpd3 plays a major regulational role in the mycotoxin production of Monascus ruber
Yunfan Zheng, Yueyan Huang, Zejing Mao, Yanchun Shao
Food Control.2022; 132: 108457. CrossRef
Characterization of key upstream asexual developmental regulators in Monascus ruber M7
Lili Jia, Yuyun Huang, Jae-Hyuk Yu, Marc Stadler, Yanchun Shao, Wanping Chen, Fusheng Chen
Food Bioscience.2022; 50: 102153. CrossRef
Quantitative Proteomics Analysis by Sequential Window Acquisition of All Theoretical Mass Spectra–Mass Spectrometry Reveals Inhibition Mechanism of Pigments and Citrinin Production of Monascus Response to High Ammonium Chloride Concentration
Bo Zhou, Yifan Ma, Yuan Tian, Jingbo Li, Haiyan Zhong
Journal of Agricultural and Food Chemistry.2020; 68(3): 808. CrossRef

A computationally simplistic poly-phasic approach to explore microbial communities from the Yucatan aquifer as a potential sources of novel natural products: Marfil-Santana Miguel David , O’Connor-Sánchez Aileen , Ramírez-Prado Jorge Humberto , De los Santos-Briones Cesar , López- Aguiar , Lluvia Korynthia , Rojas-Herrera Rafael , Lago-Lestón Asunción , Prieto-Davó Alejandra; J. Microbiol. 2016;54(11):774-781. Published online October 29, 2016; DOI: https://doi.org/10.1007/s12275-016-6092-x

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Abstract PDF

The need for new antibiotics has sparked a search for the microbes that might potentially produce them. Current sequencing technologies allow us to explore the biotechnological potential of microbial communities in diverse environments without the need for cultivation, benefitting natural product discovery in diverse ways. A relatively recent method to search for the possible production of novel compounds includes studying the diverse genes belonging to polyketide synthase pathways (PKS), as these complex enzymes are an important source of novel therapeutics. In order to explore the biotechnological potential of the microbial community from the largest underground aquifer in the world located in the Yucatan, we used a polyphasic approach in which a simple, non-computationally intensive method was coupled with direct amplification of environmental DNA to assess the diversity and novelty of PKS type I ketosynthase (KS) domains. Our results suggest that the bioinformatic method proposed can indeed be used to assess the novelty of KS enzymes; nevertheless, this in silico study did not identify some of the KS diversity due to primer bias and stringency criteria outlined by the metagenomics pipeline. Therefore, additionally implementing a method involving the direct cloning of KS domains enhanced our results. Compared to other freshwater environments, the aquifer was characterized by considerably less diversity in relation to known ketosynthase domains; however, the metagenome included a family of KS type I domains phylogenetically related, but not identical, to those found in the curamycin pathway, as well as an outstanding number of thiolases. Over all, this first look into the microbial community found in this large Yucatan aquifer and other fresh water free living microbial communities highlights the potential of these previously overlooked environments as a source of novel natural products.

Citations

Citations to this article as recorded by

Biosynthetic potential of the sediment microbial subcommunities of an unexplored karst ecosystem and its ecological implications
Pablo Suárez‐Moo, Alejandra Prieto‐Davó
MicrobiologyOpen.2024;[Epub] CrossRef
Changes in the sediment microbial community structure of coastal and inland sinkholes of a karst ecosystem from the Yucatan peninsula
Pablo Suárez-Moo, Claudia A. Remes-Rodríguez, Norma A. Márquez-Velázquez, Luisa I. Falcón, José Q. García-Maldonado, Alejandra Prieto-Davó
Scientific Reports.2022;[Epub] CrossRef
Insights into the Chemical Diversity of Selected Fungi from the Tza Itzá Cenote of the Yucatan Peninsula
Carlos A. Fajardo-Hernández, Firoz Shah Tuglak Khan, Laura Flores-Bocanegra, Alejandra Prieto-Davó, Baojie Wan, Rui Ma, Mallique Qader, Rodrigo Villanueva-Silva, Anahí Martínez-Cárdenas, Marian A. López-Lobato, Shabnam Hematian, Scott G. Franzblau, Huzefa
ACS Omega.2022; 7(14): 12171. CrossRef

Phylogenic Analysis of Alternaria brassicicola Producing Bioactive Metabolites: Dong-Sun Jung , Yeo-Jung Na , Ki Hyun Ryu; J. Microbiol. 2002;40(4):289-294.

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Abstract PDF: The fungal strain SW-3 having antimicrobial activity was isolated from soil of crucified plants in Pocheon, Kyungki-Do, Korea. Strain SW-3 was identified as Alternaria brassicicola by its morphological characteristics, and confirmed by the analysis of the 18S gene and ITS regions of rDNA. The fungus showed a similarity of 99% with Alternaria brassicicola in the 18S rDNA sequence analysis. A. brassicicola has been reported to produce an antitumor compound, called depudecin. We found that strain SW-3 produced antimicrobial metabolites, in addition to depudecin, during sporulation under different growth conditions. The metabolite of the isolated fungus was found to have strong antifungal activity against Microsporium canis and Trichophyton rubrum, and antibacterial activity against Staphylococcus aureus and Pseudomonas aerogenes. The amount and kind of metabolites produced by the isolate were affected by growth conditions such as nutrients and growth periods.

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