Pub Date : 2025-11-03DOI: 10.1007/s12223-025-01369-y
Fatma El-Saeed El-Demerdash, Osama A Mohammed, Hend H Mohamed, Ahmed S Doghish
Pregnancy induces significant alterations in the maternal microbiome, which are critical for fetal development and maternal health. Gynecological diseases, along with infertility, have increased due to excessive personal care product usage, which contains endocrine-disrupting chemicals (EDCs). Mammalian immune systems develop during pregnancy and after birth owing to crucial inputs from the environment. The growing incidence of autoimmune diseases (AIMDs) emphasizes the need to understand the environmental elements that play a role in their development, with the microbiome emerging as a key player. Exposure to EDCs with oxidative stress (OS) induces microbiome disruptions to promote AIMDs and negatively impacts female reproductive health and fetuses. Because the body changes in a number of ways to provide ideal conditions for fetal growth, pregnancy is a special moment in a woman's life. All microorganisms undergo changes, and their quantity and composition vary over the three trimesters of pregnancy. Recent research suggests a connection between pregnancy issues and the microorganisms present during pregnancy. This review explores the pivotal role of the human microbiome in pregnancy health, emphasizing how microbiome dynamics influence immune development and long-term immunity in offspring. It examines the impact of environmental factors, particularly EDCs, on maternal microbiota and their association with pregnancy complications such as hypertensive disorders and autoimmune diseases. The manuscript highlights current research findings and discusses potential microbiome-targeted interventions to promote maternal and fetal well-being.
{"title":"Microbiome alterations in healthy pregnancy and pregnancy disorders in association with autoimmune diseases.","authors":"Fatma El-Saeed El-Demerdash, Osama A Mohammed, Hend H Mohamed, Ahmed S Doghish","doi":"10.1007/s12223-025-01369-y","DOIUrl":"https://doi.org/10.1007/s12223-025-01369-y","url":null,"abstract":"<p><p>Pregnancy induces significant alterations in the maternal microbiome, which are critical for fetal development and maternal health. Gynecological diseases, along with infertility, have increased due to excessive personal care product usage, which contains endocrine-disrupting chemicals (EDCs). Mammalian immune systems develop during pregnancy and after birth owing to crucial inputs from the environment. The growing incidence of autoimmune diseases (AIMDs) emphasizes the need to understand the environmental elements that play a role in their development, with the microbiome emerging as a key player. Exposure to EDCs with oxidative stress (OS) induces microbiome disruptions to promote AIMDs and negatively impacts female reproductive health and fetuses. Because the body changes in a number of ways to provide ideal conditions for fetal growth, pregnancy is a special moment in a woman's life. All microorganisms undergo changes, and their quantity and composition vary over the three trimesters of pregnancy. Recent research suggests a connection between pregnancy issues and the microorganisms present during pregnancy. This review explores the pivotal role of the human microbiome in pregnancy health, emphasizing how microbiome dynamics influence immune development and long-term immunity in offspring. It examines the impact of environmental factors, particularly EDCs, on maternal microbiota and their association with pregnancy complications such as hypertensive disorders and autoimmune diseases. The manuscript highlights current research findings and discusses potential microbiome-targeted interventions to promote maternal and fetal well-being.</p>","PeriodicalId":12346,"journal":{"name":"Folia microbiologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hepatocellular carcinoma (HCC) remains a major clinical challenge due to its late diagnosis and poor prognosis. To address these limitations, we developed a novel gefitinib derivative (DCQ-Me) and integrated it into a multifunctional fluorescent nanosystem, AL-STEROID-CHO@DCQ-ME, designed for both targeted drug delivery and real-time tumor detection. The system exhibits ratiometric fluorescence behavior, enabling sensitive detection of the HCC biomarker GP73 through a new emission signal at 500 nm and a quantifiable intensity ratio (F500/F410), with a detection limit of 0.189 mmol L⁻¹. In vitro assays further demonstrated that AL-STEROID-CHO@DCQ-ME significantly inhibits proliferation and induces apoptosis in HCC cells. These results underline the dual functionality of the platform, offering precise diagnostic readouts alongside therapeutic efficacy. Overall, this study introduces an innovative theranostic strategy with potential to improve early detection and personalized treatment of liver cancer.
{"title":"Microbe-based fluorescent sensor composite for drug delivery and hepatocellular carcinoma suppression.","authors":"Li Li, Xianzhe Lu, Liudan Liang, Fengfei Qin, Fenglian Deng, Jize Huang, Chunyi Long, Xiaoan Ma, Qian Li, Meijin Huang, Jiannan Lv","doi":"10.1007/s12223-025-01377-y","DOIUrl":"https://doi.org/10.1007/s12223-025-01377-y","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a major clinical challenge due to its late diagnosis and poor prognosis. To address these limitations, we developed a novel gefitinib derivative (DCQ-Me) and integrated it into a multifunctional fluorescent nanosystem, AL-STEROID-CHO@DCQ-ME, designed for both targeted drug delivery and real-time tumor detection. The system exhibits ratiometric fluorescence behavior, enabling sensitive detection of the HCC biomarker GP73 through a new emission signal at 500 nm and a quantifiable intensity ratio (F500/F410), with a detection limit of 0.189 mmol L⁻¹. In vitro assays further demonstrated that AL-STEROID-CHO@DCQ-ME significantly inhibits proliferation and induces apoptosis in HCC cells. These results underline the dual functionality of the platform, offering precise diagnostic readouts alongside therapeutic efficacy. Overall, this study introduces an innovative theranostic strategy with potential to improve early detection and personalized treatment of liver cancer.</p>","PeriodicalId":12346,"journal":{"name":"Folia microbiologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31DOI: 10.1007/s12223-025-01375-0
Catherine Jose, Subramaniyan S, Sandhia G S
Salinity stress is a major constraint on global crop productivity, necessitating sustainable strategies to enhance plant resilience. Plant growth-promoting rhizobacteria (PGPR) with 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity have emerged as promising candidates for mitigating salt stress in crops. The present study evaluated the potential of PGPR isolates in improving salinity tolerance of okra (Abelmoschus esculentus L.). Growth performance, chlorophyll content, and antioxidant enzyme activities-superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT)-were assessed under salinity stress conditions. PGPR inoculation significantly enhanced growth attributes, increased chlorophyll content, and improved antioxidant enzyme activity in stressed okra plants compared to uninoculated controls. Among the tested isolates, Caballeronia sp. AS11 showed the most pronounced improvement in plant growth and oxidative stress mitigation. These findings highlight the potential of ACC deaminase-producing PGPR, particularly Caballeronia sp. AS11, as bioinoculants for enhancing salinity tolerance in okra. The application of such beneficial microbes offers a sustainable approach to improve crop productivity in saline-prone environments.
{"title":"Enhancing okra tolerance to salinity stress: role of PGPR and antioxidant enzymes.","authors":"Catherine Jose, Subramaniyan S, Sandhia G S","doi":"10.1007/s12223-025-01375-0","DOIUrl":"https://doi.org/10.1007/s12223-025-01375-0","url":null,"abstract":"<p><p>Salinity stress is a major constraint on global crop productivity, necessitating sustainable strategies to enhance plant resilience. Plant growth-promoting rhizobacteria (PGPR) with 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity have emerged as promising candidates for mitigating salt stress in crops. The present study evaluated the potential of PGPR isolates in improving salinity tolerance of okra (Abelmoschus esculentus L.). Growth performance, chlorophyll content, and antioxidant enzyme activities-superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT)-were assessed under salinity stress conditions. PGPR inoculation significantly enhanced growth attributes, increased chlorophyll content, and improved antioxidant enzyme activity in stressed okra plants compared to uninoculated controls. Among the tested isolates, Caballeronia sp. AS11 showed the most pronounced improvement in plant growth and oxidative stress mitigation. These findings highlight the potential of ACC deaminase-producing PGPR, particularly Caballeronia sp. AS11, as bioinoculants for enhancing salinity tolerance in okra. The application of such beneficial microbes offers a sustainable approach to improve crop productivity in saline-prone environments.</p>","PeriodicalId":12346,"journal":{"name":"Folia microbiologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-31DOI: 10.1007/s12223-025-01331-y
Samira Zakeer, Mariam E Amin, Gharieb S El-Sayyad, Rasha Mohammad Fathy, Ahmed I El-Batal, Shymaa Enany
Multidrug-resistant Klebsiella pneumoniae (MDR-KP) poses a significant clinical challenge due to limited therapeutic options and high mortality. This study investigated the antimicrobial efficacy of gamma-irradiation-synthesized gentamicin-conjugated silver nanoparticles (Gent-Ag NPs), copper oxide nanoparticles (CuO NPs), and bimetallic Ag-CuO NPs against three MDR-KP isolates in comparison with the gamma-irradiated gentamicin alone. Gent-Ag, Gent-CuO, and bimetallic Gent-Ag-CuO NPs were synthesized via gamma-radiation-induced reduction and characterized by different analytical methods to confirm their shape, size, surface morphology, particle size distribution, and crystallinity using HRTEM, SEM, DLS, and XRD, respectively. Comparative analysis demonstrated that Gent-Ag NPs exhibited superior antimicrobial activity, while Gent-CuO NPs showed diminished efficacy. SEM imaging analysis showed that Gent-Ag-CuO NPs effectively damaged and weakened the bacterial surfaces. It should be noted that the complete lys of K. pneumoniae cells is depicted by the white holes seen inside the bacteria. These findings suggest potential therapeutic applications of Ag-based NPs against MDR-KP, warranting further validation with larger sample sizes.
耐多药肺炎克雷伯菌(MDR-KP)由于治疗选择有限和死亡率高,构成了重大的临床挑战。本研究考察了γ辐照合成的庆大霉素共轭银纳米粒子(gen - ag NPs)、氧化铜纳米粒子(CuO NPs)和双金属Ag-CuO NPs对三种MDR-KP分离株的抗菌效果,并与γ辐照庆大霉素单独使用进行了比较。采用γ -辐射还原法制备了Gent-Ag、Gent-CuO和双金属Gent-Ag- cuo纳米粒子,并采用HRTEM、SEM、DLS和XRD等不同的分析方法对其形状、尺寸、表面形貌、粒径分布和结晶度进行了表征。对比分析表明,gen - ag NPs具有较好的抗菌活性,而gen - cuo NPs的抗菌活性较低。SEM成像分析表明,gen - ag - cuo NPs有效地破坏和削弱了细菌表面。应该注意的是,肺炎克雷伯菌细胞的完整酵母菌是由细菌内部的白洞所描绘的。这些发现提示了ag基NPs对耐多药kp的潜在治疗应用,需要用更大的样本量进一步验证。
{"title":"Antimicrobial activity of gentamicin-conjugated monometallic and bimetallic nanoparticles against multidrug-resistant Klebsiella pneumoniae strains.","authors":"Samira Zakeer, Mariam E Amin, Gharieb S El-Sayyad, Rasha Mohammad Fathy, Ahmed I El-Batal, Shymaa Enany","doi":"10.1007/s12223-025-01331-y","DOIUrl":"https://doi.org/10.1007/s12223-025-01331-y","url":null,"abstract":"<p><p>Multidrug-resistant Klebsiella pneumoniae (MDR-KP) poses a significant clinical challenge due to limited therapeutic options and high mortality. This study investigated the antimicrobial efficacy of gamma-irradiation-synthesized gentamicin-conjugated silver nanoparticles (Gent-Ag NPs), copper oxide nanoparticles (CuO NPs), and bimetallic Ag-CuO NPs against three MDR-KP isolates in comparison with the gamma-irradiated gentamicin alone. Gent-Ag, Gent-CuO, and bimetallic Gent-Ag-CuO NPs were synthesized via gamma-radiation-induced reduction and characterized by different analytical methods to confirm their shape, size, surface morphology, particle size distribution, and crystallinity using HRTEM, SEM, DLS, and XRD, respectively. Comparative analysis demonstrated that Gent-Ag NPs exhibited superior antimicrobial activity, while Gent-CuO NPs showed diminished efficacy. SEM imaging analysis showed that Gent-Ag-CuO NPs effectively damaged and weakened the bacterial surfaces. It should be noted that the complete lys of K. pneumoniae cells is depicted by the white holes seen inside the bacteria. These findings suggest potential therapeutic applications of Ag-based NPs against MDR-KP, warranting further validation with larger sample sizes.</p>","PeriodicalId":12346,"journal":{"name":"Folia microbiologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-24DOI: 10.1007/s12223-025-01346-5
Manal Mused Almatrafi, Alaa H Nada, Ahmed S Doghish, Dalia Elebeedy, Aml Ghanem, Eman Fayad, Haitham Ibrahim El-Mekkawy, Osama A Mohammed, Samy Y Elkhawaga, Dalal Sulaiman Alshaya, Fatimah Hadadi, Ahmad F Alhomodi, Muhammad Alaa Eldeen, Ahmed I Abd El Maksoud
Hyperlipidemia is a major modifiable risk factor for atherosclerosis and coronary heart disease. Although effective, current pharmacological interventions such as statins are often limited by adverse effects, including muscular pain, gastrointestinal disturbances, and increased risk of insulin resistance. Consequently, there is a growing interest in exploring safer, natural alternatives that can modulate lipid metabolism with minimal side effects. This study aimed to investigate the synergistic hypolipidemic and antioxidant effects of a combined intervention using bacterial lysates derived from Lactobacillus casei and Lactobacillus acidophilus alongside an extract of Physalis peruviana in a rat model of diet-induced hyperlipidemia. Thirty male Sprague-Dawley rats were randomly assigned to six experimental groups and treated for 7 weeks: (1) standard diet (normal control), (2) high-fat diet (HFD, hyperlipidemic control), (3) HFD + Physalis peruviana extract, (4) HFD + bacterial lysate mixture, (5) HFD + Physalis peruviana extract and bacterial lysate mixture, and (6) HFD + atorvastatin (reference drug). Lipid profiles, liver and kidney function markers, and hepatic antioxidant levels were assessed. Histopathological analyses of cardiac and hepatic tissues were also conducted. The combination of bacterial lysates and Physalis peruviana extract significantly reduced (p < 0.05) body weight, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) while significantly increasing (p < 0.05) high-density lipoprotein (HDL). This treatment also led to notable improvements in hepatic and renal function markers and enhanced hepatic antioxidant activity. Histological examination revealed reduced inflammation in cardiac and hepatic tissues of the combination-treated group, comparable to the effects observed with atorvastatin. The co-administration of Lactobacillus bacterial lysates and Physalis peruviana extract exhibited pronounced hypolipidemic and antioxidant effects, effectively mitigating diet-induced hyperlipidemia and associated organ dysfunction. These findings highlight the potential of this natural therapeutic approach as a functional alternative to conventional lipid-lowering agents in managing hyperlipidemia.
{"title":"Physalis peruviana and Lactobacillus lysates as modulators of lipid metabolism and oxidative stress: a natural alternative to statin therapy.","authors":"Manal Mused Almatrafi, Alaa H Nada, Ahmed S Doghish, Dalia Elebeedy, Aml Ghanem, Eman Fayad, Haitham Ibrahim El-Mekkawy, Osama A Mohammed, Samy Y Elkhawaga, Dalal Sulaiman Alshaya, Fatimah Hadadi, Ahmad F Alhomodi, Muhammad Alaa Eldeen, Ahmed I Abd El Maksoud","doi":"10.1007/s12223-025-01346-5","DOIUrl":"https://doi.org/10.1007/s12223-025-01346-5","url":null,"abstract":"<p><p>Hyperlipidemia is a major modifiable risk factor for atherosclerosis and coronary heart disease. Although effective, current pharmacological interventions such as statins are often limited by adverse effects, including muscular pain, gastrointestinal disturbances, and increased risk of insulin resistance. Consequently, there is a growing interest in exploring safer, natural alternatives that can modulate lipid metabolism with minimal side effects. This study aimed to investigate the synergistic hypolipidemic and antioxidant effects of a combined intervention using bacterial lysates derived from Lactobacillus casei and Lactobacillus acidophilus alongside an extract of Physalis peruviana in a rat model of diet-induced hyperlipidemia. Thirty male Sprague-Dawley rats were randomly assigned to six experimental groups and treated for 7 weeks: (1) standard diet (normal control), (2) high-fat diet (HFD, hyperlipidemic control), (3) HFD + Physalis peruviana extract, (4) HFD + bacterial lysate mixture, (5) HFD + Physalis peruviana extract and bacterial lysate mixture, and (6) HFD + atorvastatin (reference drug). Lipid profiles, liver and kidney function markers, and hepatic antioxidant levels were assessed. Histopathological analyses of cardiac and hepatic tissues were also conducted. The combination of bacterial lysates and Physalis peruviana extract significantly reduced (p < 0.05) body weight, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) while significantly increasing (p < 0.05) high-density lipoprotein (HDL). This treatment also led to notable improvements in hepatic and renal function markers and enhanced hepatic antioxidant activity. Histological examination revealed reduced inflammation in cardiac and hepatic tissues of the combination-treated group, comparable to the effects observed with atorvastatin. The co-administration of Lactobacillus bacterial lysates and Physalis peruviana extract exhibited pronounced hypolipidemic and antioxidant effects, effectively mitigating diet-induced hyperlipidemia and associated organ dysfunction. These findings highlight the potential of this natural therapeutic approach as a functional alternative to conventional lipid-lowering agents in managing hyperlipidemia.</p>","PeriodicalId":12346,"journal":{"name":"Folia microbiologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1007/s12223-025-01338-5
Jonathan Mandú de Araújo, Alícia Natalie Silva Dos Santos, Bruno José da Silva Bezerra, Vitória Camilo de Souza Silva, Wênio Sandoval Filho Lima da Silva, Amanda Vieira de Barros, Pablo Antonio Maia de Farias, Henrique Douglas Melo Coutinho, Maria Betânia de Melo Oliveira
Antimicrobial Resistance (AMR) is characterized by the reduced effectiveness of antibiotics due to the adaptation of microorganisms, which limits therapeutic options and increases the severity of infections. This paper aims to discuss therapeutic advances in combating AMR, highlighting innovative strategies, future challenges, and the importance of raising public awareness about the responsible use of antibiotics. This narrative review is based on studies from databases such as the National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus, and the Virtual Health Library, using targeted descriptors. The findings emphasize the historical shift from the pre-antibiotic era, marked by high mortality rates, to the antibiotic era, now confronted by the escalating challenge of resistance. Notable innovative strategies include the use of light-based therapies and photosensitizing agents to eradicate bacteria, the application of antimicrobial gases such as nitric oxide and ozone to reduce bacterial loads, and the development of bioactive molecules and cutting-edge technologies aimed at directly targeting resistant pathogens. Advancing these novel therapies, along with raising public awareness about the responsible use of antibiotics, is crucial to curbing the threat of AMR and safeguarding global health.
{"title":"Therapeutic advances in the fight against microbial resistance: innovative strategies and future challenges.","authors":"Jonathan Mandú de Araújo, Alícia Natalie Silva Dos Santos, Bruno José da Silva Bezerra, Vitória Camilo de Souza Silva, Wênio Sandoval Filho Lima da Silva, Amanda Vieira de Barros, Pablo Antonio Maia de Farias, Henrique Douglas Melo Coutinho, Maria Betânia de Melo Oliveira","doi":"10.1007/s12223-025-01338-5","DOIUrl":"https://doi.org/10.1007/s12223-025-01338-5","url":null,"abstract":"<p><p>Antimicrobial Resistance (AMR) is characterized by the reduced effectiveness of antibiotics due to the adaptation of microorganisms, which limits therapeutic options and increases the severity of infections. This paper aims to discuss therapeutic advances in combating AMR, highlighting innovative strategies, future challenges, and the importance of raising public awareness about the responsible use of antibiotics. This narrative review is based on studies from databases such as the National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus, and the Virtual Health Library, using targeted descriptors. The findings emphasize the historical shift from the pre-antibiotic era, marked by high mortality rates, to the antibiotic era, now confronted by the escalating challenge of resistance. Notable innovative strategies include the use of light-based therapies and photosensitizing agents to eradicate bacteria, the application of antimicrobial gases such as nitric oxide and ozone to reduce bacterial loads, and the development of bioactive molecules and cutting-edge technologies aimed at directly targeting resistant pathogens. Advancing these novel therapies, along with raising public awareness about the responsible use of antibiotics, is crucial to curbing the threat of AMR and safeguarding global health.</p>","PeriodicalId":12346,"journal":{"name":"Folia microbiologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-22DOI: 10.1007/s12223-025-01349-2
Gopal Prasad Agrawal, Md Shamsher Alam, Faisal Alotaibi, Mohammad H Alqarni, Ahmed I Foudah, Aftab Alam, Zafer Saad Al Shehri, Abdulaziz Saleh Alkhoshaiban, Faez Falah Alshehri
The emergence of multidrug-resistant (MDR) strains of Salmonella typhimurium (S. typhimurium) causes a significant global health challenge and underscores the need to develop potential antimicrobial agents. Here, we considered RamR, the major transcriptional repressor of the AcrAB-TolC efflux pump system, to identify promising inhibitors that can restore antibiotic susceptibility. We adopted an integrated computational-experimental research strategy that involved in silico screening of a structurally diverse compound database. The top four candidates (144095451, 17515455, 26648946, and 26648774) were selected for detailed analysis, which included re-docking, molecular dynamics (MD) simulations, binding free energy calculations, and free energy landscape analysis mapping. Density functional theory (DFT) was employed to explain the electronic properties and chemical reactivity of these molecules. To enhance the predictive accuracy of inhibitory potency (pIC₅₀), a machine learning (ML) regression model was developed, in which the ExtraTrees algorithm demonstrated high performance (R2 = 0.975). Among the top-ranked compounds, 144095451 emerged as the most promising RamR inhibitor, as indicated by both computational predictions and ML modelling. Experimental verification with isothermal titration calorimetry (ITC) confirmed strong binding affinity (Ka = 5.43 × 10⁶ M⁻1; ΔH = -53.18 kcal/mol; stoichiometry n = 1.74) of 144095451. Antimicrobial profiling also established its efficacy, with a minimum inhibitory concentration (MIC) of 121.65 ± 0.5 µg/mL and a zone of inhibition of 18.54 ± 0.76. These results highlight compound 144095451 as a promising RamR-targeted antimicrobial lead. This research highlights the potential of the combinatorial approach, which utilizes computational screening, structural dynamics, machine learning-based biological activity prediction, and experimental confirmation of candidate molecules against multidrug-resistant S. typhimurium.
{"title":"Structure-guided discovery and validation of a potent RamR inhibitor targeting efflux-mediated multidrug resistance in Salmonella typhimurium.","authors":"Gopal Prasad Agrawal, Md Shamsher Alam, Faisal Alotaibi, Mohammad H Alqarni, Ahmed I Foudah, Aftab Alam, Zafer Saad Al Shehri, Abdulaziz Saleh Alkhoshaiban, Faez Falah Alshehri","doi":"10.1007/s12223-025-01349-2","DOIUrl":"https://doi.org/10.1007/s12223-025-01349-2","url":null,"abstract":"<p><p>The emergence of multidrug-resistant (MDR) strains of Salmonella typhimurium (S. typhimurium) causes a significant global health challenge and underscores the need to develop potential antimicrobial agents. Here, we considered RamR, the major transcriptional repressor of the AcrAB-TolC efflux pump system, to identify promising inhibitors that can restore antibiotic susceptibility. We adopted an integrated computational-experimental research strategy that involved in silico screening of a structurally diverse compound database. The top four candidates (144095451, 17515455, 26648946, and 26648774) were selected for detailed analysis, which included re-docking, molecular dynamics (MD) simulations, binding free energy calculations, and free energy landscape analysis mapping. Density functional theory (DFT) was employed to explain the electronic properties and chemical reactivity of these molecules. To enhance the predictive accuracy of inhibitory potency (pIC₅₀), a machine learning (ML) regression model was developed, in which the ExtraTrees algorithm demonstrated high performance (R<sup>2</sup> = 0.975). Among the top-ranked compounds, 144095451 emerged as the most promising RamR inhibitor, as indicated by both computational predictions and ML modelling. Experimental verification with isothermal titration calorimetry (ITC) confirmed strong binding affinity (Ka = 5.43 × 10⁶ M⁻<sup>1</sup>; ΔH = -53.18 kcal/mol; stoichiometry n = 1.74) of 144095451. Antimicrobial profiling also established its efficacy, with a minimum inhibitory concentration (MIC) of 121.65 ± 0.5 µg/mL and a zone of inhibition of 18.54 ± 0.76. These results highlight compound 144095451 as a promising RamR-targeted antimicrobial lead. This research highlights the potential of the combinatorial approach, which utilizes computational screening, structural dynamics, machine learning-based biological activity prediction, and experimental confirmation of candidate molecules against multidrug-resistant S. typhimurium.</p>","PeriodicalId":12346,"journal":{"name":"Folia microbiologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bloodstream infections (BSIs) represent a significant clinical challenge due to their high morbidity and mortality rates, compounded by the increasing prevalence of antimicrobial resistance (AMR). Even though they are regarded as the gold standard, traditional diagnostic techniques like blood cultures frequently have low sensitivity and delayed findings. Rapid molecular diagnostics (RMDs) have completely changed how BSIs are identified and treated. By using cutting-edge methods like next-generation sequencing (NGS), loop-mediated isothermal amplification (LAMP), polymerase chain reaction (PCR), and microarray-based approaches, RMDs allow for the quick, precise, and thorough identification of pathogens and resistance markers straight from blood samples. By drastically cutting down on diagnostic delays, these technologies enable early targeted therapy start, better clinical results, and less need on broad-spectrum antibiotics, which are the primary cause of AMR. Additionally, advancements like NGS improve diagnostic accuracy by offering profound insights into pathogen genomes, virulence factors, and resistance mechanisms. Barriers including high prices, integration difficulties, and the requirement for specialized knowledge prevent them from being widely adopted, despite their transformational potential. Nevertheless, these issues are being addressed by continuous developments in automation and point-of-care (POC) systems, which should make RMDs more affordable and widely available. In order to improve therapeutic accuracy, reduce AMR, and advance infection control techniques, this research emphasizes the crucial role that RMDs play in the management of BSI. In order to improve customized medicine strategies, future initiatives include streamlining diagnostic processes and combining molecular diagnostics with clinical decision support technologies.
{"title":"The role of rapid molecular diagnostics in managing bloodstream infections: a microbiological insight.","authors":"Jitendra Gupta, Ibrahim Saeed Gataa, Narinderjit Singh Sawaran Singh, G PadmaPriya, Subhashree Ray, Amrita Pal, Vimal Arora, Aseel Smerat, Akmal Abilkasimov, Mutabar Latipova","doi":"10.1007/s12223-025-01367-0","DOIUrl":"https://doi.org/10.1007/s12223-025-01367-0","url":null,"abstract":"<p><p>Bloodstream infections (BSIs) represent a significant clinical challenge due to their high morbidity and mortality rates, compounded by the increasing prevalence of antimicrobial resistance (AMR). Even though they are regarded as the gold standard, traditional diagnostic techniques like blood cultures frequently have low sensitivity and delayed findings. Rapid molecular diagnostics (RMDs) have completely changed how BSIs are identified and treated. By using cutting-edge methods like next-generation sequencing (NGS), loop-mediated isothermal amplification (LAMP), polymerase chain reaction (PCR), and microarray-based approaches, RMDs allow for the quick, precise, and thorough identification of pathogens and resistance markers straight from blood samples. By drastically cutting down on diagnostic delays, these technologies enable early targeted therapy start, better clinical results, and less need on broad-spectrum antibiotics, which are the primary cause of AMR. Additionally, advancements like NGS improve diagnostic accuracy by offering profound insights into pathogen genomes, virulence factors, and resistance mechanisms. Barriers including high prices, integration difficulties, and the requirement for specialized knowledge prevent them from being widely adopted, despite their transformational potential. Nevertheless, these issues are being addressed by continuous developments in automation and point-of-care (POC) systems, which should make RMDs more affordable and widely available. In order to improve therapeutic accuracy, reduce AMR, and advance infection control techniques, this research emphasizes the crucial role that RMDs play in the management of BSI. In order to improve customized medicine strategies, future initiatives include streamlining diagnostic processes and combining molecular diagnostics with clinical decision support technologies.</p>","PeriodicalId":12346,"journal":{"name":"Folia microbiologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1007/s12223-025-01362-5
Runheng Zhao, Wenfang Liu, Ke Wang, Hongxia Li, Haiyuan Li
Prostate cancer remains a major global health challenge, driving the need for innovative therapies. Nisin, an antimicrobial peptide from Lactobacillus lactis, has shown anticancer effects in various malignancies, yet its impact on prostate cancer and the prostate cancer antigen 3 (PCA3) long non-coding RNA (lncRNA) remains unstudied. This research aimed to investigate nisin's anticancer properties in prostate cancer cells, focusing on PCA3 lncRNA, apoptosis, and cell cycle pathways. Human prostate adenocarcinoma (LNCaP) and normal human foreskin fibroblast (HFF2) cells were treated with nisin. Cell viability was measured using MTT assays, while apoptosis and cell cycle progression were assessed via flow cytometry. Quantitative PCR (qPCR) evaluated gene expression of PCA3 lncRNA, apoptosis-related genes, cell cycle regulators, and PCA3-associated microRNAs and mRNAs. In-silico analysis of TCGA-PRAD data explored PCA3's regulatory network. Nisin selectively reduced LNCaP cell viability (IC₅₀: 370.7 μM at 24 h, 177.2 μM at 48 h) compared to HFF2 cells (IC₅₀: 887.8 μM at 24 h, 406.5 μM at 48 h). It induced time-dependent apoptosis and G1 phase cell cycle arrest in LNCaP cells. Nisin downregulated PCA3 lncRNA expression, upregulated miR-132-3p and miR-1261, and altered SREBP1 and PRKD3 gene expression, modulating the PCA3 regulatory network. This study is the first to explore nisin's anticancer effects in prostate cancer, uniquely targeting PCA3 lncRNA and its downstream regulatory pathways. Nisin demonstrates potent anticancer effects in prostate cancer cells by inducing apoptosis, arresting cell cycle progression, and modulating the PCA3 lncRNA network, suggesting its potential as a novel therapeutic agent.
{"title":"Nisin: The powerhouse metabolite of lactobacillus strains to defeat prostate cancer by targeting PCA3 lncRNA, apoptosis, and cell cycle pathways.","authors":"Runheng Zhao, Wenfang Liu, Ke Wang, Hongxia Li, Haiyuan Li","doi":"10.1007/s12223-025-01362-5","DOIUrl":"https://doi.org/10.1007/s12223-025-01362-5","url":null,"abstract":"<p><p>Prostate cancer remains a major global health challenge, driving the need for innovative therapies. Nisin, an antimicrobial peptide from Lactobacillus lactis, has shown anticancer effects in various malignancies, yet its impact on prostate cancer and the prostate cancer antigen 3 (PCA3) long non-coding RNA (lncRNA) remains unstudied. This research aimed to investigate nisin's anticancer properties in prostate cancer cells, focusing on PCA3 lncRNA, apoptosis, and cell cycle pathways. Human prostate adenocarcinoma (LNCaP) and normal human foreskin fibroblast (HFF2) cells were treated with nisin. Cell viability was measured using MTT assays, while apoptosis and cell cycle progression were assessed via flow cytometry. Quantitative PCR (qPCR) evaluated gene expression of PCA3 lncRNA, apoptosis-related genes, cell cycle regulators, and PCA3-associated microRNAs and mRNAs. In-silico analysis of TCGA-PRAD data explored PCA3's regulatory network. Nisin selectively reduced LNCaP cell viability (IC₅₀: 370.7 μM at 24 h, 177.2 μM at 48 h) compared to HFF2 cells (IC₅₀: 887.8 μM at 24 h, 406.5 μM at 48 h). It induced time-dependent apoptosis and G1 phase cell cycle arrest in LNCaP cells. Nisin downregulated PCA3 lncRNA expression, upregulated miR-132-3p and miR-1261, and altered SREBP1 and PRKD3 gene expression, modulating the PCA3 regulatory network. This study is the first to explore nisin's anticancer effects in prostate cancer, uniquely targeting PCA3 lncRNA and its downstream regulatory pathways. Nisin demonstrates potent anticancer effects in prostate cancer cells by inducing apoptosis, arresting cell cycle progression, and modulating the PCA3 lncRNA network, suggesting its potential as a novel therapeutic agent.</p>","PeriodicalId":12346,"journal":{"name":"Folia microbiologica","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}