Pub Date : 2024-09-23DOI: 10.1080/17460913.2024.2398904
Francisco Es Lopes, Pedro Fn Souza, Daiane Ms Brito, Felipe P Mesquita, Raquel C Montenegro, Jackson L Amaral, José Ha Filho, Valder N Freire, Rossana A Cordeiro
Aim: Synthetic antimicrobial peptides (SAMPs) present the potential to fight systemic fungal infections. Here, the PHO36 receptor from Candida albicans was analyzed by in silico tools as a possible target for three anticandidal SAMPs: RcAlb-PepIII, PepGAT and PepKAA.Materials & methods: Molecular docking, dynamics and quantum biochemistry were employed to understand the individual contribution of amino acid residues in the interaction region.Results: The results revealed that SAMPs strongly interact with the PHO36 by multiple high-energy interactions. This is the first study to employ quantum biochemistry to describe the interactions between SAMPs and the PHO36 receptor.Conclusion: This work contributes to understanding and identifying new molecular targets with medical importance that could be used to discover new drugs against systemic fungal infections.
{"title":"<i>In silico</i> approach revealed the membrane receptor PHO36 as a new target for synthetic anticandidal peptides.","authors":"Francisco Es Lopes, Pedro Fn Souza, Daiane Ms Brito, Felipe P Mesquita, Raquel C Montenegro, Jackson L Amaral, José Ha Filho, Valder N Freire, Rossana A Cordeiro","doi":"10.1080/17460913.2024.2398904","DOIUrl":"https://doi.org/10.1080/17460913.2024.2398904","url":null,"abstract":"<p><p><b>Aim:</b> Synthetic antimicrobial peptides (SAMPs) present the potential to fight systemic fungal infections. Here, the PHO36 receptor from <i>Candida albicans</i> was analyzed by <i>in silico</i> tools as a possible target for three anticandidal SAMPs: <i>Rc</i>Alb-PepIII, PepGAT and PepKAA.<b>Materials & methods:</b> Molecular docking, dynamics and quantum biochemistry were employed to understand the individual contribution of amino acid residues in the interaction region.<b>Results:</b> The results revealed that SAMPs strongly interact with the PHO36 by multiple high-energy interactions. This is the first study to employ quantum biochemistry to describe the interactions between SAMPs and the PHO36 receptor.<b>Conclusion:</b> This work contributes to understanding and identifying new molecular targets with medical importance that could be used to discover new drugs against systemic fungal infections.</p>","PeriodicalId":12773,"journal":{"name":"Future microbiology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284399","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 : 2024-09-13DOI: 10.1080/17460913.2024.2398332
Jovana Chiapetti Tartari, Asif Khan, João Gabriel da Silva Andrade, Francielli Abigail Vilugron Rodrigues, Paulo Sérgio Alves Bueno, Diego de Souza Lima, Fernanda Canduri, Gisele de Freitas Gauze, Érika Seki Kioshima, Flavio Augusto Vicente Seixas
Aim: To search for potential inhibitors to homoserine dehydrogenase (HSD) in Paracoccidioides brasiliensis the causative agent of paracoccidioidomycosis, an infection with a high mortality rate in Brazil.Materials & methods: The enzyme was modeled and used in the virtual screening of the compounds. The library was first screened by the Autodock, in which 66 molecules were better ranked than substrate, and then, also evaluated by the Molegro and Gold programs.Results: The HS23 and HS87 molecules were selected in common by the three programs, and ADME/Tox evaluation indicates they are not toxic. The molecular dynamics of PbHSD bonded to ligands showed stable complexes until 50 ns. To validate the results, compounds were purchased for assays of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), synergic profile with Amphotericin B (AmB) and cytotoxicity. The two molecules presented MIC of 32 μg/ml and MFC of 64 μg/ml against the P. brasiliensis (strain Pb18). They also showed synergistic activity with AmB and a lack of toxicity against Hela and Vero cell lines.Conclusion: These results suggest that the HS23 and HS87 are promising candidates as PbHSD inhibitors and may be used as hits for the development of new drugs against paracoccidioidomycosis.
目的:寻找巴西副球孢子菌病(Paracoccidioidomycosis)的潜在同丝氨酸脱氢酶(HSD)抑制剂:对酶进行建模,并将其用于化合物的虚拟筛选。首先用 Autodock 对化合物库进行筛选,其中 66 个分子的排名优于底物,然后用 Molegro 和 Gold 程序进行评估:结果:HS23 和 HS87 分子被三个程序共同选中,并且 ADME/Tox 评估表明它们没有毒性。与配体结合的 PbHSD 的分子动力学显示,在 50 毫微秒之前,复合物是稳定的。为了验证结果,购买了化合物进行最低抑菌浓度(MIC)、最低杀菌浓度(MFC)、与两性霉素 B(AmB)的协同作用以及细胞毒性的检测。这两种分子对巴西痢疾杆菌(Pb18 株)的 MIC 为 32 μg/ml,MFC 为 64 μg/ml。它们还显示出与 AmB 的协同活性,且对 Hela 和 Vero 细胞系无毒性:这些结果表明,HS23 和 HS87 是很有希望的 PbHSD 抑制剂候选物,可作为开发抗副球孢子菌病新药的靶点。
{"title":"Predicting of novel homoserine dehydrogenase inhibitors against <i>Paracoccidioides brasiliensis</i>: integrating <i>in silico</i> and <i>in vitro</i> approaches.","authors":"Jovana Chiapetti Tartari, Asif Khan, João Gabriel da Silva Andrade, Francielli Abigail Vilugron Rodrigues, Paulo Sérgio Alves Bueno, Diego de Souza Lima, Fernanda Canduri, Gisele de Freitas Gauze, Érika Seki Kioshima, Flavio Augusto Vicente Seixas","doi":"10.1080/17460913.2024.2398332","DOIUrl":"https://doi.org/10.1080/17460913.2024.2398332","url":null,"abstract":"<p><p><b>Aim:</b> To search for potential inhibitors to homoserine dehydrogenase (HSD) in <i>Paracoccidioides brasiliensis</i> the causative agent of paracoccidioidomycosis, an infection with a high mortality rate in Brazil.<b>Materials & methods:</b> The enzyme was modeled and used in the virtual screening of the compounds. The library was first screened by the Autodock, in which 66 molecules were better ranked than substrate, and then, also evaluated by the Molegro and Gold programs.<b>Results:</b> The HS23 and HS87 molecules were selected in common by the three programs, and ADME/Tox evaluation indicates they are not toxic. The molecular dynamics of <i>Pb</i>HSD bonded to ligands showed stable complexes until 50 ns. To validate the results, compounds were purchased for assays of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), synergic profile with Amphotericin B (AmB) and cytotoxicity. The two molecules presented MIC of 32 μg/ml and MFC of 64 μg/ml against the <i>P. brasiliensis</i> (strain Pb18). They also showed synergistic activity with AmB and a lack of toxicity against Hela and Vero cell lines.<b>Conclusion:</b> These results suggest that the HS23 and HS87 are promising candidates as <i>Pb</i>HSD inhibitors and may be used as hits for the development of new drugs against paracoccidioidomycosis.</p>","PeriodicalId":12773,"journal":{"name":"Future microbiology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284404","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}
Microbes are a major source of enzymes due to their ability to be mass-cultivated and genetically modified. Compared with plant and animal enzymes, microbial enzymes are more stable and active. Enzymes are generally classified into six classes based on their reaction, substrate specificity and mechanism of action. In addition to their application in medicine for treating diseases, these compounds are used as anti-inflammatory, thrombolytic and digestive agents. However, challenges such as immunogenicity, tissue specificity and short in vivo half-life make clinical trials complex. Enzymes are metabolic catalysts in industry and their production and extraction must be optimized to preserve profitability due to rising demand. The present review highlights the increasing importance of bacterial enzymes in industry and medicine and explores methods for their production, extraction and purification.
{"title":"Application of microbial enzymes in medicine and industry: current status and future perspectives.","authors":"Atieh Darbandi, Zahra Elahi, Leila Dadgar-Zankbar, Fatemeh Ghasemi, Naser Kakavandi, Sajjad Jafari, Talieh Darbandi, Roya Ghanavati","doi":"10.1080/17460913.2024.2398337","DOIUrl":"https://doi.org/10.1080/17460913.2024.2398337","url":null,"abstract":"<p><p>Microbes are a major source of enzymes due to their ability to be mass-cultivated and genetically modified. Compared with plant and animal enzymes, microbial enzymes are more stable and active. Enzymes are generally classified into six classes based on their reaction, substrate specificity and mechanism of action. In addition to their application in medicine for treating diseases, these compounds are used as anti-inflammatory, thrombolytic and digestive agents. However, challenges such as immunogenicity, tissue specificity and short <i>in vivo</i> half-life make clinical trials complex. Enzymes are metabolic catalysts in industry and their production and extraction must be optimized to preserve profitability due to rising demand. The present review highlights the increasing importance of bacterial enzymes in industry and medicine and explores methods for their production, extraction and purification.</p>","PeriodicalId":12773,"journal":{"name":"Future microbiology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284401","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 : 2024-09-13DOI: 10.1080/17460913.2024.2398410
Sarah Fakher, David Westenberg
Aim: Healthcare-acquired infections (HAIs) pose significant challenges in medical settings due to their resistance to conventional treatment methods. The role of bacterial biofilms in exacerbating these infections is well-documented, making HAIs particularly difficult to eradicate. Despite numerous research efforts, an effective solution to combat these infections remains elusive. This study aims to explore the potential of metal-ion (copper and zinc) doped borate bioactive glasses (BBGs) as a novel treatment modality to inhibit bacterial species commonly implicated in HAIs: Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa.Methods: The study analyzed the efficacy of both direct and indirect applications of BBGs on severe biofilms pre-formed under static and dynamic growth conditions; a comprehensive predictive modeling was developed, simulating diverse clinically relevant conditions.Results: Results demonstrate more than 4 log reduction in bacterial growth within 2 days for direct application and 3 days for indirect application of copper and zinc-doped BBGs. These findings were consistent across the three bacterial species, in both static and dynamic conditions.Conclusion: Copper and zinc-doped BBGs can be an effective approach in combating HAIs complicated by biofilms.
{"title":"The anti-biofilm efficacy of copper and zinc doped borate bioactive glasses.","authors":"Sarah Fakher, David Westenberg","doi":"10.1080/17460913.2024.2398410","DOIUrl":"https://doi.org/10.1080/17460913.2024.2398410","url":null,"abstract":"<p><p><b>Aim:</b> Healthcare-acquired infections (HAIs) pose significant challenges in medical settings due to their resistance to conventional treatment methods. The role of bacterial biofilms in exacerbating these infections is well-documented, making HAIs particularly difficult to eradicate. Despite numerous research efforts, an effective solution to combat these infections remains elusive. This study aims to explore the potential of metal-ion (copper and zinc) doped borate bioactive glasses (BBGs) as a novel treatment modality to inhibit bacterial species commonly implicated in HAIs: <i>Staphylococcus epidermidis</i>, <i>Escherichia coli</i>, and <i>Pseudomonas aeruginosa</i>.<b>Methods:</b> The study analyzed the efficacy of both direct and indirect applications of BBGs on severe biofilms pre-formed under static and dynamic growth conditions; a comprehensive predictive modeling was developed, simulating diverse clinically relevant conditions.<b>Results:</b> Results demonstrate more than 4 log reduction in bacterial growth within 2 days for direct application and 3 days for indirect application of copper and zinc-doped BBGs. These findings were consistent across the three bacterial species, in both static and dynamic conditions.<b>Conclusion:</b> Copper and zinc-doped BBGs can be an effective approach in combating HAIs complicated by biofilms.</p>","PeriodicalId":12773,"journal":{"name":"Future microbiology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284405","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}
Aim:Mycoplasma pneumoniae (MP) is a common cause of respiratory infections, and its incidence has increased post-COVID-19 due to "immune debt." Real-time quantitative polymerase chain reaction (qPCR) is the standard for detecting MP, but it has a lengthy detection time. This study aimed to establish a highly sensitive rapid detection method for MP.Materials & methods: We developed an integrated assay combining multienzyme isothermal rapid amplification (MIRA) with qPCR, referred to as MIRA-qPCR, for the rapid detection of MP, delivering results within approximately 40 min.Results: The analytic sensitivity of the MIRA-qPCR assay was 10 copies per reaction, and it exhibited no cross-reactivity with other respiratory pathogens, ensuring high specificity. Clinical sample analysis demonstrated higher sensitivity for MIRA-qPCR compared to qPCR reported in the literature, and 100% concordance with commercial qPCR kit.Conclusion: The MIRA-qPCR method established in this study is a promising tool for the clinical detection of MP, offering significant advantages for the rapid diagnosis of MP infections.
{"title":"Establishment and evaluation of MIRA-qPCR assay for the rapid and sensitively detection of <i>Mycoplasma pneumoniae</i>.","authors":"Qiao Qiao, Yi-Yue Ge, Xiao-Juan Zhu, Kang-Chen Zhao, Yin Chen, Lun-Biao Cui, Tao Wu","doi":"10.1080/17460913.2024.2398886","DOIUrl":"https://doi.org/10.1080/17460913.2024.2398886","url":null,"abstract":"<p><p><b>Aim:</b> <i>Mycoplasma pneumoniae</i> (MP) is a common cause of respiratory infections, and its incidence has increased post-COVID-19 due to \"immune debt.\" Real-time quantitative polymerase chain reaction (qPCR) is the standard for detecting MP, but it has a lengthy detection time. This study aimed to establish a highly sensitive rapid detection method for MP.<b>Materials & methods:</b> We developed an integrated assay combining multienzyme isothermal rapid amplification (MIRA) with qPCR, referred to as MIRA-qPCR, for the rapid detection of MP, delivering results within approximately 40 min.<b>Results:</b> The analytic sensitivity of the MIRA-qPCR assay was 10 copies per reaction, and it exhibited no cross-reactivity with other respiratory pathogens, ensuring high specificity. Clinical sample analysis demonstrated higher sensitivity for MIRA-qPCR compared to qPCR reported in the literature, and 100% concordance with commercial qPCR kit.<b>Conclusion:</b> The MIRA-qPCR method established in this study is a promising tool for the clinical detection of MP, offering significant advantages for the rapid diagnosis of MP infections.</p>","PeriodicalId":12773,"journal":{"name":"Future microbiology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284402","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 : 2024-09-11DOI: 10.1080/17460913.2024.2392454
Abozar Nasiri-Jahrodi, Mehdi Barati, Fatemeh-Maryam Sheikholeslami, Mona Fani, Azin Nikoozadeh
This study reports the first case of lung and fungus ball lesions caused by Cladosporium subcinereum A48. A rural diabetic woman infected by C. subcinereum A48, presented with fever and hemoptysis. CT scans, bronchoalveolar lavage, culture and molecular methods were used to evaluate and confirm the disease. Our patient had not taken insulin during the last few months of her life which probably caused acidosis and a decrease in the patient's immunity level, resulting in penetration and formation of a fungal in the lung.
{"title":"A case of lung and fungus ball lesions associated with <i>Cladosporium Subcinereum A48</i> in a diabetic patient.","authors":"Abozar Nasiri-Jahrodi, Mehdi Barati, Fatemeh-Maryam Sheikholeslami, Mona Fani, Azin Nikoozadeh","doi":"10.1080/17460913.2024.2392454","DOIUrl":"https://doi.org/10.1080/17460913.2024.2392454","url":null,"abstract":"<p><p>This study reports the first case of lung and fungus ball lesions caused by <i>Cladosporium subcinereum A48</i>. A rural diabetic woman infected by <i>C. subcinereum A48</i>, presented with fever and hemoptysis. CT scans, bronchoalveolar lavage, culture and molecular methods were used to evaluate and confirm the disease. Our patient had not taken insulin during the last few months of her life which probably caused acidosis and a decrease in the patient's immunity level, resulting in penetration and formation of a fungal in the lung.</p>","PeriodicalId":12773,"journal":{"name":"Future microbiology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284400","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 : 2024-09-11DOI: 10.1080/17460913.2024.2398312
João Paulo Salvaterra Pasquini, Paula Assis Queiroz, Pedro Henrique Rodrigues do Amaral, Thalita Camilo da Silva, Patricia de Souza Bonfim Mendonça, Fábio Vandresen, João Pedro Carvalho Ceolis, Regiane Bertin de Lima Scodro, Katiany Rizzieri Caleffi-Ferracioli, Rosilene Fressatti Cardoso, Vera Lúcia Dias Siqueira
Aim: Polymyxin B (PMB) is one of the few therapeutic options for treating infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the emergence of PMB-resistant CR-GNB strains has prompted the exploration of antibiotic adjuvants as potential therapeutic avenues. Thus, this study evaluates the potential of 3,5-dinitrobenzoic acid derivatives (DNH01, DNH11, DNH13 and DNH20) and isoniazid-N-acylhydrazones (INZ1-7, INZ9 and INZ11) as adjuvants to enhance PMB efficacy against CR-GNB.Materials & methods: MIC, MBC and drug combination assays were conducted using multidrug-resistant clinical isolates of Enterobacterales and Acinetobacter baumannii. In addition, the effects of PMB and PMB + DNH derivatives were assessed through flow cytometry and scanning electron microscopy (SEM).Results: DNH01, DNH11 and DNH20, unlike the INH-acylhydrazones, significantly restored PMB activity (MIC ≤ 2 μg/ml) in 80% of the tested isolates. Flow cytometry and SEM assays confirmed that DNH derivatives rescued the activity of PMB, yielding results comparable to those expected for PMB alone but at 256-fold lower concentrations.Conclusion: These findings suggest DNH derivatives hold substantial promise as PMB adjuvants to combat PMB-resistant CR-GNB infections.
{"title":"Polymyxin B adjuvants against polymyxin B- and carbapenem-resistant Gram-negative bacteria.","authors":"João Paulo Salvaterra Pasquini, Paula Assis Queiroz, Pedro Henrique Rodrigues do Amaral, Thalita Camilo da Silva, Patricia de Souza Bonfim Mendonça, Fábio Vandresen, João Pedro Carvalho Ceolis, Regiane Bertin de Lima Scodro, Katiany Rizzieri Caleffi-Ferracioli, Rosilene Fressatti Cardoso, Vera Lúcia Dias Siqueira","doi":"10.1080/17460913.2024.2398312","DOIUrl":"https://doi.org/10.1080/17460913.2024.2398312","url":null,"abstract":"<p><p><b>Aim:</b> Polymyxin B (PMB) is one of the few therapeutic options for treating infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the emergence of PMB-resistant CR-GNB strains has prompted the exploration of antibiotic adjuvants as potential therapeutic avenues. Thus, this study evaluates the potential of 3,5-dinitrobenzoic acid derivatives (DNH01, DNH11, DNH13 and DNH20) and isoniazid-<i>N</i>-acylhydrazones (INZ1-7, INZ9 and INZ11) as adjuvants to enhance PMB efficacy against CR-GNB.<b>Materials & methods:</b> MIC, MBC and drug combination assays were conducted using multidrug-resistant clinical isolates of <i>Enterobacterales</i> and <i>Acinetobacter baumannii</i>. In addition, the effects of PMB and PMB + DNH derivatives were assessed through flow cytometry and scanning electron microscopy (SEM).<b>Results:</b> DNH01, DNH11 and DNH20, unlike the INH-acylhydrazones, significantly restored PMB activity (MIC ≤ 2 μg/ml) in 80% of the tested isolates. Flow cytometry and SEM assays confirmed that DNH derivatives rescued the activity of PMB, yielding results comparable to those expected for PMB alone but at 256-fold lower concentrations.<b>Conclusion:</b> These findings suggest DNH derivatives hold substantial promise as PMB adjuvants to combat PMB-resistant CR-GNB infections.</p>","PeriodicalId":12773,"journal":{"name":"Future microbiology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284403","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 : 2024-09-05DOI: 10.1080/17460913.2024.2389750
Preeti Maurya, Mohit Kumar, Ravi Jain, Haider Thaer Abdulhameed Almuqdadi, Harshita Singh, Aashima Gupta, Christoph Arenz, Naseem A Gaur, Shailja Singh
Aim: To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; 'PfMFSDT') as a drug transporter, using Candida glabrata for orthologous protein expression.Methods: Complementary Determining Sequence encoding PfMFSDT was integrated into the genome of genetically engineered C. glabrata strain MSY8 via homologous recombination, followed by assessing its functional relevance as a drug transporter.Results & conclusion: The modified C. glabrata strain exhibited plasma membrane localization of PfMFSDT and characteristics of an Major Facilitator Superfamily transporter, conferring resistance to antifungals, ketoconazole and itraconazole. The nanomolar inhibitory effects of the drugs on the intra-erythrocytic growth of Plasmodium falciparum highlight their antimalarial properties. This study proposes PfMFSDT as a drug transporter, expanding the repertoire of the currently known antimalarial 'resistome'.
{"title":"Expression of <i>Plasmodium</i> major facilitator superfamily protein in transporters - Δ <i>Candida</i> identifies a drug transporter.","authors":"Preeti Maurya, Mohit Kumar, Ravi Jain, Haider Thaer Abdulhameed Almuqdadi, Harshita Singh, Aashima Gupta, Christoph Arenz, Naseem A Gaur, Shailja Singh","doi":"10.1080/17460913.2024.2389750","DOIUrl":"https://doi.org/10.1080/17460913.2024.2389750","url":null,"abstract":"<p><p><b>Aim:</b> To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; '<i>Pf</i>MFSDT') as a drug transporter, using <i>Candida glabrata</i> for orthologous protein expression.<b>Methods:</b> Complementary Determining Sequence encoding <i>Pf</i>MFSDT was integrated into the genome of genetically engineered <i>C. glabrata</i> strain MSY8 via homologous recombination, followed by assessing its functional relevance as a drug transporter.<b>Results & conclusion:</b> The modified <i>C. glabrata</i> strain exhibited plasma membrane localization of <i>Pf</i>MFSDT and characteristics of an Major Facilitator Superfamily transporter, conferring resistance to antifungals, ketoconazole and itraconazole. The nanomolar inhibitory effects of the drugs on the intra-erythrocytic growth of <i>Plasmodium falciparum</i> highlight their antimalarial properties. This study proposes <i>Pf</i>MFSDT as a drug transporter, expanding the repertoire of the currently known antimalarial 'resistome'.</p>","PeriodicalId":12773,"journal":{"name":"Future microbiology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132538","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 : 2024-09-05DOI: 10.1080/17460913.2024.2390286
Helaine Almeida Queiroz, Lisandra Juvêncio da Silva, Fátima Daiana Dias Barroso, Lívia Gurgel do Amaral Valente Sá, João Batista de Andrade Neto, Érica Rayanne Motta da Costa, Leilson Carvalho de Oliveira, Amanda Dias Barbosa, Vitória Pessoa de Farias Cabral, Daniel Sampaio Rodrigues, Lara Elloyse Almeida Moreira, Bruno Coêlho Cavalcanti, Islay Lima Magalhães, Manoel Odorico de Moraes, Hélio Vitoriano Nobre Júnior, Cecília Rocha da Silva
Aim: To evaluate the antifungal activity of amlodipine against strains of Candida spp. and to its possible mechanism of action.Methods: Broth microdilution tests were used to determine the minimum inhibitory concentration, while the synergistic activity was evaluated by calculating the fractional inhibitory concentration index. The action of amlodipine against biofilms was determined using the MTT assay and its possible mechanism of action was investigated through flow cytometry tests.Results: Amlodipine showed MICs ranging from 62.5 to 250 μg/ml, in addition to action against pre-formed and forming biofilms, with reductions between 50 and 90%. Amlodipine increases the externalization of phosphatidylserine and reduces the cell viability of fungal cells, suggesting apoptosis.Conclusion: Amlodipine had good antifungal activity against planktonic cells and biofilms of Candida spp., by leading the cells to apoptosis.
{"title":"Evaluation of amlodipine against strains of <i>Candida</i> spp. in planktonic cells, developing biofilms and mature biofilms.","authors":"Helaine Almeida Queiroz, Lisandra Juvêncio da Silva, Fátima Daiana Dias Barroso, Lívia Gurgel do Amaral Valente Sá, João Batista de Andrade Neto, Érica Rayanne Motta da Costa, Leilson Carvalho de Oliveira, Amanda Dias Barbosa, Vitória Pessoa de Farias Cabral, Daniel Sampaio Rodrigues, Lara Elloyse Almeida Moreira, Bruno Coêlho Cavalcanti, Islay Lima Magalhães, Manoel Odorico de Moraes, Hélio Vitoriano Nobre Júnior, Cecília Rocha da Silva","doi":"10.1080/17460913.2024.2390286","DOIUrl":"https://doi.org/10.1080/17460913.2024.2390286","url":null,"abstract":"<p><p><b>Aim:</b> To evaluate the antifungal activity of amlodipine against strains of <i>Candida</i> spp. and to its possible mechanism of action.<b>Methods:</b> Broth microdilution tests were used to determine the minimum inhibitory concentration, while the synergistic activity was evaluated by calculating the fractional inhibitory concentration index. The action of amlodipine against biofilms was determined using the MTT assay and its possible mechanism of action was investigated through flow cytometry tests.<b>Results:</b> Amlodipine showed MICs ranging from 62.5 to 250 μg/ml, in addition to action against pre-formed and forming biofilms, with reductions between 50 and 90%. Amlodipine increases the externalization of phosphatidylserine and reduces the cell viability of fungal cells, suggesting apoptosis.<b>Conclusion:</b> Amlodipine had good antifungal activity against planktonic cells and biofilms of <i>Candida</i> spp., by leading the cells to apoptosis.</p>","PeriodicalId":12773,"journal":{"name":"Future microbiology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132537","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}
Enterococcus, particularly E. faecium and E. faecalis, are responsible for many hospital-acquired infections. With their intrinsic antibiotic resistance and ability to form biofilms, enterococcal infections are already challenging to manage. However, when heterogenous populations are present, such as those exhibiting heteroresistance and persistence, the complexity of these infections increases exponentially not only due to their treatment but also due to their difficult diagnosis. In this study, we provide a summary of the current understanding of both heteroresistance and persistence in terms of mechanisms, diagnosis and treatment and subsequently review recent literature pertaining to these susceptibility types specifically in enterococci.
{"title":"Antibiotic heteroresistance and persistence: an additional aid in hospital acquired infections by <i>Enterococcus</i> spp.?","authors":"Catarina Geraldes, Luís Tavares, Solange Gil, Manuela Oliveira","doi":"10.1080/17460913.2024.2393003","DOIUrl":"https://doi.org/10.1080/17460913.2024.2393003","url":null,"abstract":"<p><p><i>Enterococcus</i>, particularly <i>E. faecium</i> and <i>E. faecalis</i>, are responsible for many hospital-acquired infections. With their intrinsic antibiotic resistance and ability to form biofilms, enterococcal infections are already challenging to manage. However, when heterogenous populations are present, such as those exhibiting heteroresistance and persistence, the complexity of these infections increases exponentially not only due to their treatment but also due to their difficult diagnosis. In this study, we provide a summary of the current understanding of both heteroresistance and persistence in terms of mechanisms, diagnosis and treatment and subsequently review recent literature pertaining to these susceptibility types specifically in enterococci.</p>","PeriodicalId":12773,"journal":{"name":"Future microbiology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125497","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}