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Transcriptional regulator-based biosensors for biomanufacturing in Corynebacterium glutamicum
IF 6.1 1区 生物学
Microbiological research Pub Date : 2025-04-05 DOI: 10.1016/j.micres.2025.128169
Jie Liu , Wei-Guo Zhang , Zhi-Ming Rao
{"title":"Transcriptional regulator-based biosensors for biomanufacturing in Corynebacterium glutamicum","authors":"Jie Liu ,&nbsp;Wei-Guo Zhang ,&nbsp;Zhi-Ming Rao","doi":"10.1016/j.micres.2025.128169","DOIUrl":"10.1016/j.micres.2025.128169","url":null,"abstract":"<div><div>Intracellular biosensors based on transcriptional regulators have become essential instruments in biomanufacturing, extensively employed for the semi-quantitative assessment of intracellular metabolites, high-throughput screening of production strains, and the directed evolution of enzymes. <em>Corynebacterium glutamicum</em> serves as an industrial chassis for the production of amino acids and a variety of high-value-added chemicals. This paper discusses the varieties and modes of action of transcriptional regulators employed in the construction of intracellular biosensors in <em>C. glutamicum</em>. It also reviews the design principles and progress in the application of transcriptional regulator-based biosensors. Furthermore, measures designed to improve the efficacy of these biosensors are delineated. The challenges and future prospects of biosensors based on transcriptional regulators in practical applications are analyzed. This review seeks to offer theoretical direction for the systematic design and development of transcriptional regulator-based biosensors and to aid researchers in enhancing the growth and productivity of microbial production strains.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128169"},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Trojan horse strategy and TfR/ LDLR-Mediated transcytosis determine the dissemination of mycobacteria in tuberculous meningoencephalitis
IF 6.1 1区 生物学
Microbiological research Pub Date : 2025-04-04 DOI: 10.1016/j.micres.2025.128172
Ziyi Liu, Yuanzhi Wang, Yuhui Dong, Haoran Wang, Zhengmin Liang, Ruichao Yue, Xiangmei Zhou
{"title":"Trojan horse strategy and TfR/ LDLR-Mediated transcytosis determine the dissemination of mycobacteria in tuberculous meningoencephalitis","authors":"Ziyi Liu,&nbsp;Yuanzhi Wang,&nbsp;Yuhui Dong,&nbsp;Haoran Wang,&nbsp;Zhengmin Liang,&nbsp;Ruichao Yue,&nbsp;Xiangmei Zhou","doi":"10.1016/j.micres.2025.128172","DOIUrl":"10.1016/j.micres.2025.128172","url":null,"abstract":"<div><div>Tuberculous meningoencephalitis (TBM), caused by the Mycobacterium tuberculosis complex, stands as one of the most lethal infections affecting the central nervous system (CNS). The understanding of the mechanisms underlying the neuroinvasion of Mycobacterium bovis (<em>M. bovis</em>) remains limited. Our findings reveal that <em>M. bovis</em> could exploit host transferrin receptor (TfR)- and low-density lipoprotein receptor (LDLR)-mediated transcytosis, while simultaneously utilizing infected macrophages as vectors to traverse the blood-brain barrier (BBB). Infected macrophages accelerate the <em>M. bovis’</em> neuroinvasion and promote its proliferation and dissemination to various organs. Persistent infection disrupts BBB integrity by degrading tight junction proteins and upregulating intercellular cell adhesion molecule-1 (iCAM-1), facilitating macrophage adhesion and migration, which contribute to the pathogen’s entry into the brain. This study established a murine TBM model by administering <em>M. bovis</em> through carotid artery injection, accurately mimicking the interactions between the pathogen and the BBB. These findings offer insights into the mechanisms of TBM and serve as a foundation for developing targeted therapeutic strategies.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128172"},"PeriodicalIF":6.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plant growth-promoting microorganisms: New insights and the way forward 植物生长促进微生物:新的认识和前进方向
IF 6.1 1区 生物学
Microbiological research Pub Date : 2025-04-03 DOI: 10.1016/j.micres.2025.128168
Parissa Taheri , Gerardo Puopolo , Gustavo Santoyo
{"title":"Plant growth-promoting microorganisms: New insights and the way forward","authors":"Parissa Taheri ,&nbsp;Gerardo Puopolo ,&nbsp;Gustavo Santoyo","doi":"10.1016/j.micres.2025.128168","DOIUrl":"10.1016/j.micres.2025.128168","url":null,"abstract":"<div><div>In the context of global challenges such as climate change, soil degradation, and food security, understanding the modes of action of Plant Growth-Promoting Microorganisms (PGPMs), their formulation, and their application is crucial and can be more focused in future research projects. This editorial paper aims to elucidate diverse modes of action employed by different types of PGPMs, including nitrogen fixation, phosphorus solubilization, production or regulation of phytohormones, and plant protection against environmental and biotic stresses as demonstrated and discussed in the Special Issue entitled “Plant Growth-Promoting Microorganisms: new insights and the way forward”.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128168"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clostridium butyricum ameliorates post-gastrectomy insulin resistance by regulating the mTORC1 signaling pathway through the gut-liver axis
IF 6.1 1区 生物学
Microbiological research Pub Date : 2025-04-03 DOI: 10.1016/j.micres.2025.128154
Zhipeng He , Huan Xiong , Yujie Cai , Wenjing Chen , Meng Shi , Lulin Liu , Kai Wu , Xi Deng , Xiaorong Deng , Tingtao Chen
{"title":"Clostridium butyricum ameliorates post-gastrectomy insulin resistance by regulating the mTORC1 signaling pathway through the gut-liver axis","authors":"Zhipeng He ,&nbsp;Huan Xiong ,&nbsp;Yujie Cai ,&nbsp;Wenjing Chen ,&nbsp;Meng Shi ,&nbsp;Lulin Liu ,&nbsp;Kai Wu ,&nbsp;Xi Deng ,&nbsp;Xiaorong Deng ,&nbsp;Tingtao Chen","doi":"10.1016/j.micres.2025.128154","DOIUrl":"10.1016/j.micres.2025.128154","url":null,"abstract":"<div><div>Postoperative insulin resistance (IR) is a metabolic disorder characterized by decreased insulin sensitivity and elevated blood glucose levels following major surgery. Our previous clinical study identified a notable correlation between postoperative IR and gut microbiota, particularly butyrate-producing bacteria, yet the mechanisms remain unclear. In this study, we established gastric resection SD rat models to evaluate the impact of <em>Clostridium butyricum</em> NCU-27 (butyrate-producing bacteria) on postoperative IR. The results demonstrated significant reductions in fasting blood glucose (FBG), fasting insulin (FIns) levels, and HOMA-IR (6.64 ± 0.76 vs. 11.47 ± 1.32; 4.27 ± 0.59 vs. 7.40 ± 0.54) in the postoperative period compared to the control group (<em>P</em> &lt; 0.05). Additionally, glucose tolerance and hepatic glycogen content were markedly improved (<em>P</em> &lt; 0.001). Further exploration of butyrate demonstrated effects similar to <em>C. butyricum</em> NCU-27, potentially mediated through the gut-liver axis by inhibiting mTORC1 expression in liver cells, activating the IRS1/AKT pathway, enhancing glucose uptake and glycogen synthesis, suppressing gluconeogenesis, increasing insulin sensitivity, and improving IR. Finally, the use of mTORC1 agonists and inhibitors further confirmed the critical role of the mTORC1 pathway in mediating the beneficial effects of <em>C. butyricum</em> NCU-27 and butyrate on postoperative IR. In conclusion, this study elucidated that <em>C. butyricum</em> NCU-27 improves postoperative IR by regulating butyrate metabolism and inhibiting the mTORC1 pathway, offering new insights for preventing and treating post-gastrectomy IR.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128154"},"PeriodicalIF":6.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Rhizobium etli response regulator CenR is essential for both: Free-life and the rhizobial nitrogen-fixing symbiosis
IF 6.1 1区 生物学
Microbiological research Pub Date : 2025-03-29 DOI: 10.1016/j.micres.2025.128159
María M. Banda , M.P. Elizabeth Salas-Ocampo , Marisa Rodríguez , Sofía Martínez-Absalón , Alfonso Leija-Salas , Rocío Reyero-Saavedra , Mishael Sánchez-Pérez , Georgina Hernández , Dimitris Georgellis , Ayari Fuentes-Hernández , Lourdes Girard
{"title":"The Rhizobium etli response regulator CenR is essential for both: Free-life and the rhizobial nitrogen-fixing symbiosis","authors":"María M. Banda ,&nbsp;M.P. Elizabeth Salas-Ocampo ,&nbsp;Marisa Rodríguez ,&nbsp;Sofía Martínez-Absalón ,&nbsp;Alfonso Leija-Salas ,&nbsp;Rocío Reyero-Saavedra ,&nbsp;Mishael Sánchez-Pérez ,&nbsp;Georgina Hernández ,&nbsp;Dimitris Georgellis ,&nbsp;Ayari Fuentes-Hernández ,&nbsp;Lourdes Girard","doi":"10.1016/j.micres.2025.128159","DOIUrl":"10.1016/j.micres.2025.128159","url":null,"abstract":"<div><div>The canonical two-component systems (TCS) consist of a histidine kinase and a response regulator that work together to control various pathways in bacteria. Rhizobia are rod-shaped, Gram-negative alpha-proteobacteria capable of establishing a nitrogen-fixing symbiosis with compatible legume hosts. These bacteria can live freely in the soil or as intracellular symbionts within root nodules. Here, we characterized an orphan OmpR-type response regulator in <em>Rhizobium etli</em> CE3, which we renamed CenR due to its similarity to CenR proteins known as essential regulators of cell envelope-related functions in alpha-proteobacteria. We identified the cognate histidine kinase encoded by <em>cenK</em>, located in a separate genomic region from <em>cenR</em>. CenR and CenK form a TCS that has not been previously reported in <em>Rhizobium</em>. Our results indicate that the overexpression of <em>cenR</em> as well as the absence of <em>cenK,</em> negatively impacts <em>R. etli</em> growth and cell morphology, while bacteria overexpressing <em>cenR</em> also exhibit uncoordinated cell division. Furthermore, we demonstrated that the CenKR TCS directly or indirectly regulates the expression of essential genes involved in pathways that control cell growth and morphology. Electrophoretic mobility shift assays confirmed that CenR binds directly to the promoter regions of two uncharacterized genes in <em>R. etli</em>. Furthermore, analysis of the <em>R. etli</em> - common bean (<em>Phaseolus vulgaris</em>) symbiosis revealed increased infection threads, reduced leghemoglobin content, and lower nitrogen fixation efficiency in nodules infected by the <em>cenR</em>-overexpressing strain. In conclusion, our findings revealed that the CenKR TCS coordinates important cell cycle events in <em>Rhizobium</em> that are vital for both free-living and symbiotic conditions.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128159"},"PeriodicalIF":6.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pathogen-derived peptidoglycan skeleton enhances innate immune defense against Staphylococcus aureus via mTOR-HIF-1α-HK2-mediated trained immunity
IF 6.1 1区 生物学
Microbiological research Pub Date : 2025-03-29 DOI: 10.1016/j.micres.2025.128160
Zheng Jia , Lingdi Niu , Junjie Guo , Jiaqing Wang , Hai Li , Runhang Liu , Ning Liu , Shuhe Zhang , Fang Wang , Junwei Ge
{"title":"Pathogen-derived peptidoglycan skeleton enhances innate immune defense against Staphylococcus aureus via mTOR-HIF-1α-HK2-mediated trained immunity","authors":"Zheng Jia ,&nbsp;Lingdi Niu ,&nbsp;Junjie Guo ,&nbsp;Jiaqing Wang ,&nbsp;Hai Li ,&nbsp;Runhang Liu ,&nbsp;Ning Liu ,&nbsp;Shuhe Zhang ,&nbsp;Fang Wang ,&nbsp;Junwei Ge","doi":"10.1016/j.micres.2025.128160","DOIUrl":"10.1016/j.micres.2025.128160","url":null,"abstract":"<div><div>Regulation of the innate immune response may be an effective strategy to enhance <em>Staphylococcus aureus</em> vaccines. Based on our previous findings that the <em>Listeria</em> peptidoglycan skeleton (pBLP) enhances the immune response through an unknown mechanism, we hypothesized that pBLP provides protection by modulating the innate immune response via trained immunity. In vitro, pBLP increased phagocytosis and inflammatory cytokine levels and elevated the anti-inflammatory cytokine TGF-β following secondary stimulation. In an in vivo model, our findings indicate that pBLP, when administered with a vaccine, protects mice from methicillin-resistant <em>S. aureus</em> challenge and also provides protection against <em>S. aureus</em> CMCC26003 in the absence of antigens. Using an ex vivo model, we demonstrated that pBLP increases markers of trained immunity in peritoneal macrophages. Transcriptome analysis of differentially expressed genes and inhibitor experiments revealed that the trained immunity process induced by pBLP depends on mTOR-HIF-1α and hexokinase 2. This study is the first to demonstrate that pBLP can induce trained immunity. Furthermore, we show that the peptidoglycan skeleton induces a distinct trained immunity phenotype compared to β-glucan, enhancing vaccine protection. Our study provides valuable insights for the design of novel vaccines that integrate both specific and innate immune responses.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"296 ","pages":"Article 128160"},"PeriodicalIF":6.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Salt-alkali-tolerant growth-promoting Streptomyces sp. Jrh8-9 enhances alfalfa growth and resilience under saline-alkali stress through integrated modulation of photosynthesis, antioxidant defense, and hormone signaling 耐盐碱促生长链霉菌 Jrh8-9 通过综合调节光合作用、抗氧化防御和激素信号,提高苜蓿在盐碱胁迫下的生长和抗逆能力
IF 6.1 1区 生物学
Microbiological research Pub Date : 2025-03-28 DOI: 10.1016/j.micres.2025.128158
Lifeng Guo , Xuchen Zhang , Yaning Liu , Aiqin Zhang , Wenshuai Song , Lixin Li , Junwei Zhao , Qiuying Pang
{"title":"Salt-alkali-tolerant growth-promoting Streptomyces sp. Jrh8-9 enhances alfalfa growth and resilience under saline-alkali stress through integrated modulation of photosynthesis, antioxidant defense, and hormone signaling","authors":"Lifeng Guo ,&nbsp;Xuchen Zhang ,&nbsp;Yaning Liu ,&nbsp;Aiqin Zhang ,&nbsp;Wenshuai Song ,&nbsp;Lixin Li ,&nbsp;Junwei Zhao ,&nbsp;Qiuying Pang","doi":"10.1016/j.micres.2025.128158","DOIUrl":"10.1016/j.micres.2025.128158","url":null,"abstract":"<div><div><em>Streptomyces</em> is a group of plant growth-promoting microorganisms with considerable potential for enhancing plant tolerance to environmental stress. However, the mechanisms by which <em>Streptomyces</em> strains induce systemic tolerance to saline-alkaline stress remain unclear. Here, we evaluated the properties of <em>Streptomyces</em> sp. Jrh8–9, isolated from the halophyte rhizosphere soil, and its effects on alfalfa growth and response to saline-alkali stress. Jrh8–9 exhibited multiple plant-beneficial traits, including phosphate solubilization, nitrogen fixation, indole-3-acetic acid production, and high saline-alkali tolerance. Jrh8–9 inoculation considerably promoted growth in stressed alfalfa by increasing shoot fresh weight, root fresh weight, leaf area, plant height, root length, and root vigor by 46.7 %, 250.8 %, 36.0 %, 31.8 %, 47.4 %, and 103.0 %, respectively. It also improved the chlorophyll content, maximum photochemical efficiency of photosystem II, and the net photosynthetic rate. Physiological and biochemical analyses revealed that Jrh8–9 facilitated ion homeostasis by reducing Na<sup>+</sup> and increasing Mg<sup>2+</sup> levels, improving osmotic regulation by increasing soluble sugar and relative water contents, and enhancing antioxidant defenses by increasing superoxide dismutase, catalase, and ascorbate peroxidase activities. Transcriptomic profiling identified key differentially expressed genes associated with auxin and jasmonic acid signaling in response to Jrh8–9 inoculation, with auxin- and jasmonic acid-related genes linked to antioxidant pathways. Further analysis showed that increased auxin and jasmonic acid levels induced by Jrh8–9 mitigated reactive oxygen species accumulation and supported photosynthetic function. These findings highlight the multifaceted mechanisms underlying <em>Streptomyces</em>-induced saline-alkali tolerance and provide a potential strategy for improving forage crop resilience in saline-alkali soils.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"296 ","pages":"Article 128158"},"PeriodicalIF":6.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling the potential of bioengineered microbiome-based strategies to enhance cancer immunotherapy
IF 6.1 1区 生物学
Microbiological research Pub Date : 2025-03-28 DOI: 10.1016/j.micres.2025.128156
Muhammad Hamza , Shuai Wang , Yike Liu , Kun Li , Motao Zhu , Lin Chen
{"title":"Unraveling the potential of bioengineered microbiome-based strategies to enhance cancer immunotherapy","authors":"Muhammad Hamza ,&nbsp;Shuai Wang ,&nbsp;Yike Liu ,&nbsp;Kun Li ,&nbsp;Motao Zhu ,&nbsp;Lin Chen","doi":"10.1016/j.micres.2025.128156","DOIUrl":"10.1016/j.micres.2025.128156","url":null,"abstract":"<div><div>The human microbiome plays a pivotal role in the field of cancer immunotherapy. The microbial communities that inhabit the gastrointestinal tract, as well as the bacterial populations within tumors, have been identified as key modulators of therapeutic outcomes, affecting immune responses and reprogramming the tumor microenvironment. Advances in synthetic biology have made it possible to reprogram and engineer these microorganisms to improve antitumor activity, enhance T-cell function, and enable targeted delivery of therapies to neoplasms. This review discusses the role of the microbiome in modulating both innate and adaptive immune mechanisms—ranging from the initiation of cytokine production and antigen presentation to the regulation of immune checkpoints—and discusses how these mechanisms improve the efficacy of immune checkpoint inhibitors. We highlight significant advances with bioengineered strains like <em>Escherichia coli</em> Nissle 1917<em>, Lactococcus lactis, Bifidobacterium,</em> and <em>Bacteroides</em>, which have shown promising antitumor efficacy in preclinical models. These engineered microorganisms not only efficiently colonize tumor tissues but also help overcome resistance to standard therapies by reprogramming the local immune environment. Nevertheless, several challenges remain, such as the requirement for genetic stability, effective tumor colonization, and the control of potential safety issues. In the future, the ongoing development of genetic engineering tools and the optimization of bacterial delivery systems are crucial for the translation of microbiome-based therapies into the clinic. This review highlights the potential of bioengineered microbiota as an innovative, personalized approach in cancer immunotherapy, bringing hope for more effective and personalized treatment options for patients with advanced malignancies.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"296 ","pages":"Article 128156"},"PeriodicalIF":6.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Streptococcus suis regulates central carbon fluxes in response to environment to balance drug resistance and virulence
IF 6.1 1区 生物学
Microbiological research Pub Date : 2025-03-28 DOI: 10.1016/j.micres.2025.128157
Shuo Yuan , Baobao Liu , Yingying Quan , Shuji Gao , Jing Zuo , Wenjie Jin , Yamin Shen , Yue Li , Yuxin Wang , Yang Wang
{"title":"Streptococcus suis regulates central carbon fluxes in response to environment to balance drug resistance and virulence","authors":"Shuo Yuan ,&nbsp;Baobao Liu ,&nbsp;Yingying Quan ,&nbsp;Shuji Gao ,&nbsp;Jing Zuo ,&nbsp;Wenjie Jin ,&nbsp;Yamin Shen ,&nbsp;Yue Li ,&nbsp;Yuxin Wang ,&nbsp;Yang Wang","doi":"10.1016/j.micres.2025.128157","DOIUrl":"10.1016/j.micres.2025.128157","url":null,"abstract":"<div><div><em>Streptococcus suis</em>, a zoonotic pathogen, must adapt to the distinct nutritional environment of the host microhabitat during infection and the establishment of invasive disease, primarily by modulating its metabolic pathways. Metabolic plasticity endows <em>S. suis</em> with an enhanced capacity for environmental adaptation. Multidrug-resistant <em>S. suis</em> is increasingly prevalent due to the extensive use of antibiotics in swine production. In this study, an environment-dependent evolutionary model demonstrated that <em>S. suis</em> could modulate its metabolism in response to environmental changes, thereby altering its drug resistance and virulence. The central carbon flux regulated by pyruvate dehydrogenase (PDH) was identified as a pivotal node in balancing drug resistance and virulence in <em>S. suis</em>. Within the in vivo host environment, increased carbon flux through PDH enhances the production of capsular polysaccharide (CPS), thereby improving immune evasion. Conversely, in the antibiotic environment, reduced carbon flux through PDH downregulates the bacterial metabolic state, which diminishes the induction of toxic metabolites by antibiotics, thereby augmenting drug resistance. This concept provides a reasonable explanation for the puzzling phenomena observed with <em>S. suis</em> in clinical settings. For instance, antibiotic-resistant <em>S. suis</em> has a survival advantage in pig farms where antibiotics are frequently used but is less frequently associated with invasive infections. Furthermore, this study demonstrates that exogenous pyruvate can enhance the bactericidal effect of gentamicin against clinically multidrug-resistant <em>S. suis</em>, offering new insights and potential strategies for controlling clinical multidrug-resistant <em>S. suis</em> infections.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"296 ","pages":"Article 128157"},"PeriodicalIF":6.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ArcAB system promotes biofilm formation through direct repression of hapR transcription in Vibrio cholerae
IF 6.1 1区 生物学
Microbiological research Pub Date : 2025-03-28 DOI: 10.1016/j.micres.2025.128155
Jant Cres Caigoy , Hirofumi Nariya , Toshi Shimamoto , Zhiqun Yan , Tadashi Shimamoto
{"title":"ArcAB system promotes biofilm formation through direct repression of hapR transcription in Vibrio cholerae","authors":"Jant Cres Caigoy ,&nbsp;Hirofumi Nariya ,&nbsp;Toshi Shimamoto ,&nbsp;Zhiqun Yan ,&nbsp;Tadashi Shimamoto","doi":"10.1016/j.micres.2025.128155","DOIUrl":"10.1016/j.micres.2025.128155","url":null,"abstract":"<div><div><em>Vibrio cholerae,</em> the causative agent of cholera, can efficiently adapt its metabolic processes, including biofilm formation, in response to varying respiratory conditions— such as aerobic, microaerobic, and anaerobic— through the ArcAB system. In this study, we elucidate the activation mechanism of <em>V. cholerae</em> ArcB and ArcA and identify ArcB residues H292, D577, and H722, along with ArcA residue D54 as key phosphorylation sites. Furthermore, we demonstrate that the ArcAB system plays a crucial role in regulating biofilm formation under both aerobic and anaerobic conditions. Our findings reveal that the positive regulation of biofilm formation by the ArcAB systems involves the high cell density (HCD) quorum sensing (QS) regulator HapR. Specifically, phosphorylated ArcA represses <em>hapR</em> transcription, thereby promoting biofilm formation under anaerobic condition. This study also highlights an epistatic relationship between ArcA and HapR in biofilm regulation. Overall, our results underscore the critical role of the ArcAB system in the biofilm formation of pathogenic <em>V. cholerae</em> under oxygen-limiting conditions.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"297 ","pages":"Article 128155"},"PeriodicalIF":6.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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