Current GeneticsPub Date : 2023-12-01Epub Date: 2023-06-03DOI: 10.1007/s00294-023-01272-4
Dionysios Patriarcheas, Taizina Momtareen, Jennifer E G Gallagher
{"title":"Yeast of Eden: microbial resistance to glyphosate from a yeast perspective.","authors":"Dionysios Patriarcheas, Taizina Momtareen, Jennifer E G Gallagher","doi":"10.1007/s00294-023-01272-4","DOIUrl":"10.1007/s00294-023-01272-4","url":null,"abstract":"<p><p>First marketed as RoundUp, glyphosate is history's most popular herbicide because of its low acute toxicity to metazoans and broad-spectrum effectiveness across plant species. The development of glyphosate-resistant crops has led to increased glyphosate use and consequences from the use of glyphosate-based herbicides (GBH). Glyphosate has entered the food supply, spurred glyphosate-resistant weeds, and exposed non-target organisms to glyphosate. Glyphosate targets EPSPS/AroA/Aro1 (orthologs across plants, bacteria, and fungi), the rate-limiting step in the production of aromatic amino acids from the shikimate pathway. Metazoans lacking this pathway are spared from acute toxicity and acquire their aromatic amino acids from their diet. However, glyphosate resistance is increasing in non-target organisms. Mutations and natural genetic variation discovered in Saccharomyces cerevisiae illustrate similar types of glyphosate resistance mechanisms in fungi, plants, and bacteria, in addition to known resistance mechanisms such as mutations in Aro1 that block glyphosate binding (target-site resistance (TSR)) and mutations in efflux drug transporters non-target-site resistance (NTSR). Recently, genetic variation and mutations in an amino transporter affecting glyphosate resistance have uncovered potential off-target effects of glyphosate in fungi and bacteria. While glyphosate is a glycine analog, it is transported into cells using an aspartic/glutamic acid (D/E) transporter. The size, shape, and charge distribution of glyphosate closely resembles D/E, and, therefore, glyphosate is a D/E amino acid mimic. The mitochondria use D/E in several pathways and mRNA-encoding mitochondrial proteins are differentially expressed during glyphosate exposure. Mutants downstream of Aro1 are not only sensitive to glyphosate but also a broad range of other chemicals that cannot be rescued by exogenous supplementation of aromatic amino acids. Glyphosate also decreases the pH when unbuffered and many studies do not consider the differences in pH that affect toxicity and resistance mechanisms.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":" ","pages":"203-212"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10716058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10100464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current GeneticsPub Date : 2023-12-01Epub Date: 2023-09-19DOI: 10.1007/s00294-023-01274-2
Liqin Fan, Xinxin Li, Hongli Li, Bingjie Li, Jiahui Wang, Le He, Zhongkang Wang, Yunlong Lin
{"title":"Comparative transcriptome analysis to unveil genes affecting the host cuticle destruction in Metarhizium rileyi.","authors":"Liqin Fan, Xinxin Li, Hongli Li, Bingjie Li, Jiahui Wang, Le He, Zhongkang Wang, Yunlong Lin","doi":"10.1007/s00294-023-01274-2","DOIUrl":"10.1007/s00294-023-01274-2","url":null,"abstract":"<p><p>Insect pathogenic fungi, also known as entomopathogenic fungi, are one of the largest insect pathogenic microorganism communities, represented by Beauveria spp. and Metarhizium spp. Entomopathogenic fungi have been proved to be a great substitute for chemical pesticide in agriculture. In fact, a lot of functional genes were also already characterized in entomopathogenic fungi, but more depth of exploration is still needed to reveal their complicated pathogenic mechanism to insects. Metarhizium rileyi (Nomuraea rileyi) is a great potential biocontrol fungus that can parasitize more than 40 distinct species (mainly Lepidoptera: Noctuidae) to cause large-scale infectious diseases within insect population. In this study, a comparative analysis of transcriptome profile was performed with topical inoculation and hemolymph injection to character the infectious pattern of M. rileyi. Appressorium and multiple hydrolases are indispensable constituents to break the insect host primary cuticle defense in entomopathogenic fungi. Within our transcriptome data, numerous transcripts related to destruction of insect cuticle rather growth regulations were obtained. Most importantly, some unreported ribosomal protein genes and novel unannotated protein (hypothetical protein) genes were proved to participate in the course of pathogenic regulation. Our current data provide a higher efficiency gene library for virulence factors screen in M. rileyi, and this library may be also useful for furnishing valuable information on entomopathogenic fungal pathogenic mechanisms to host.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":" ","pages":"253-265"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135122","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}
Current GeneticsPub Date : 2023-12-01Epub Date: 2023-11-08DOI: 10.1007/s00294-023-01276-0
Diana Khananisho, Alister J Cumming, Daria Kulakova, Patrick J Shilling, Daniel O Daley
{"title":"Tips for efficiently maintaining pET expression plasmids.","authors":"Diana Khananisho, Alister J Cumming, Daria Kulakova, Patrick J Shilling, Daniel O Daley","doi":"10.1007/s00294-023-01276-0","DOIUrl":"10.1007/s00294-023-01276-0","url":null,"abstract":"<p><p>pET expression plasmids are widely used for producing recombinant proteins in Escherichia coli. Selection and maintenance of cells harboring a pET plasmid are possible using either a Tn3.1-type genetic fragment (which encodes a ß-lactamase and confers resistance to ß-lactam antibiotics) or a Tn903.1-type genetic fragment (which encodes an aminoglycoside-3'-phosphotransferase and confers resistance aminoglycoside antibiotics). Herein we have investigated how efficiently pET plasmids are maintained using these two fragments. The study reveals that pET plasmids are efficiently maintained with both Tn3.1 and Tn903.1 genetic fragments prior to the induction of recombinant protein production, and over short induction times (i.e., 2 h). However, over longer induction times (i.e., 20 h), the efficiency of plasmid maintenance depends on the host strain used, and the type of antibiotic selection cassette used. Based on our collective observations, we have 2 general tips for efficiently maintaining pET plasmids during recombinant production experiments. Tip #1: Use a strain with lowered levels of the T7 RNA polymerase, such as C41(DE3). pET plasmids will be efficiently maintained over long induction times with both the Tn3.1 and Tn903.1 genetic fragments, regardless of whether antibiotics are present during cultivation. Tip #2: If a strain with higher levels of T7 RNA polymerase strain is necessary, such as BL21(DE3)), keep induction times short or use a plasmid containing a Tn903.1-type fragment and select with kanamycin.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":" ","pages":"277-287"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10716060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current GeneticsPub Date : 2023-12-01Epub Date: 2023-05-26DOI: 10.1007/s00294-023-01271-5
Ghazal Aziz, Arsalan Zaidi, Daniel J O ' Sullivan
{"title":"Insights from metagenome-assembled genomes on the genetic stability and safety of over-the-counter probiotic products.","authors":"Ghazal Aziz, Arsalan Zaidi, Daniel J O ' Sullivan","doi":"10.1007/s00294-023-01271-5","DOIUrl":"10.1007/s00294-023-01271-5","url":null,"abstract":"<p><p>The demand for and acceptance of probiotics is determined by their quality and safety. Illumina NGS sequencing and analytics were used to examine eight marketed probiotics. Up to the species level, sequenced DNA was taxonomically identified, and relative abundances were determined using Kaiju. The genomes were constructed using GTDB and validated through PATRICK and TYGS. A FastTree 2 phylogenetic tree was constructed using several type strain sequences from relevant species. Bacteriocin and ribosomally synthesized polypeptide (RiPP) genes were discovered, and a safety check was performed to test for toxins, antibiotic resistance, and genetic drift genes. Except for two products with unclaimed species, the labeling was taxonomically correct. In three product formulations, Lactobacillus acidophilus, Limosilactobacillus reuteri, Lacticaseibacillus paracasei, and Bifidobacterium animalis exhibited two to three genomic alterations, while Streptococcus equinus was found in one. TYGS and GDTB discovered E. faecium and L. paracasei in distinctly different ways. All the bacteria tested had the genetic repertoire to tolerate GIT transit, although some exhibited antibiotic resistance, and one strain had two virulence genes. Except for Bifidobacterium strains, the others revealed a variety of bacteriocins and ribosomally synthesized polypeptides (RiPP), 92% of which were unique and non-homologous to known ones. Plasmids and mobile genetic elements are present in strains of L. reuteri (NPLps01.et_L.r and NPLps02.uf_L.r), Lactobacillus delbrueckii (NPLps01.et_L.d), Streptococcus thermophilus (NPLps06.ab_S.t), and E. faecium (NPLps07.nf_E.f). Our findings support the use of metagenomics to build better and efficient production and post-production practices for probiotic quality and safety assessment.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":" ","pages":"213-234"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9529294","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}
Current GeneticsPub Date : 2023-12-01Epub Date: 2023-06-22DOI: 10.1007/s00294-023-01273-3
Kholoud Shaban, Andrew Dolson, Ashley Fisher, Emma Lessard, Safia Mahabub Sauty, Krassimir Yankulov
{"title":"TOF1 and RRM3 reveal a link between gene silencing and the pausing of replication forks.","authors":"Kholoud Shaban, Andrew Dolson, Ashley Fisher, Emma Lessard, Safia Mahabub Sauty, Krassimir Yankulov","doi":"10.1007/s00294-023-01273-3","DOIUrl":"10.1007/s00294-023-01273-3","url":null,"abstract":"<p><p>Eukaryotic DNA replication is accompanied by the disassembly and reassembly of nucleosomes and the transmission of epigenetic marks to the newly assembled chromatids. Several histone chaperones, including CAF-1 and Asf1p, are central to these processes. On the other hand, replication forks pause at numerous positions throughout the genome, but it is not known if and how this pausing affects the reassembly and maintenance of chromatin structures. Here, we applied drug-free gene silencing assays to analyze the genetic interactions between CAC1, ASF1, and two genes that regulate the stability of the paused replisome (TOF1) and the resumption of elongation (RRM3). Our results show that TOF1 and RRM3 differentially interact with CAF-1 and ASF1 and that the deletions of TOF1 and RRM3 lead to reduced silencing and increased frequency of epigenetic conversions at three loci in the genome of S. cerevisiae. Our study adds details to the known activities of CAF-1 and Asf1p and suggests that the pausing of the replication fork can lead to epigenetic instability.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":" ","pages":"235-249"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677261","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}
Current GeneticsPub Date : 2023-12-01Epub Date: 2023-11-10DOI: 10.1007/s00294-023-01277-z
Maike Engelhardt, Stefan Hintze, Eva-Carina Wendegatz, Julia Lettow, Hans-Joachim Schüller
{"title":"Ino2, activator of yeast phospholipid biosynthetic genes, interacts with basal transcription factors TFIIA and Bdf1.","authors":"Maike Engelhardt, Stefan Hintze, Eva-Carina Wendegatz, Julia Lettow, Hans-Joachim Schüller","doi":"10.1007/s00294-023-01277-z","DOIUrl":"10.1007/s00294-023-01277-z","url":null,"abstract":"<p><p>Binding of general transcription factors TFIID and TFIIA to basal promoters is rate-limiting for transcriptional initiation of eukaryotic protein-coding genes. Consequently, activator proteins interacting with subunits of TFIID and/or TFIIA can drastically increase the rate of initiation events. Yeast transcriptional activator Ino2 interacts with several Taf subunits of TFIID, among them the multifunctional Taf1 protein. In contrast to mammalian Taf1, yeast Taf1 lacks bromodomains which are instead encoded by separate proteins Bdf1 and Bdf2. In this work, we show that Bdf1 not only binds to acetylated histone H4 but can also be recruited by Ino2 and unrelated activators such as Gal4, Rap1, Leu3 and Flo8. An activator-binding domain was mapped in the N-terminus of Bdf1. Subunits Toa1 and Toa2 of yeast TFIIA directly contact sequences of basal promoters and TFIID subunit TBP but may also mediate the influence of activators. Indeed, Ino2 efficiently binds to two separate structural domains of Toa1, specifically with its N-terminal four-helix bundle structure required for dimerization with Toa2 and its C-terminal β-barrel domain contacting TBP and sequences of the TATA element. These findings complete the functional analysis of yeast general transcription factors Bdf1 and Toa1 and identify them as targets of activator proteins.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":" ","pages":"289-300"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10716077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72013875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of human BRCA2 in Saccharomyces cerevisiae complements the loss of RAD52 in double-strand break repair.","authors":"Sherrice Law, Hannah Park, Eyar Shany, Sumer Sandhu, Mayukha Vallabhaneni, Damon Meyer","doi":"10.1007/s00294-023-01278-y","DOIUrl":"10.1007/s00294-023-01278-y","url":null,"abstract":"<p><p>BRCA2 is a tumor-suppressor gene that is normally expressed in the breast and ovarian tissue of mammals. The BRCA2 protein mediates the repair of double-strand breaks (DSBs) using homologous recombination, which is a conserved pathway in eukaryotes. Women who express missense mutations in the BRCA2 gene are predisposed to an elevated lifetime risk for both breast cancer and ovarian cancer. In the present study, the efficiency of human BRCA2 (hBRCA2) in DSB repair was investigated in the budding yeast Saccharomyces cerevisiae. While budding yeast does not possess a true BRCA2 homolog, they have a potential functional homolog known as Rad52, which is an essential repair protein involved in mediating homologous recombination using the same mechanism as BRCA2 in humans. Therefore, to examine the functional overlap between Rad52 in yeast and hBRCA2, we expressed the wild-type hBRCA2 gene in budding yeast with or without Rad52 and monitored ionizing radiation resistance and DSB repair efficiency. We found that the expression of hBRCA2 in rad52 mutants increases both radiation resistance and DSB repair frequency compared to cells not expressing BRCA2. Specifically, BRCA2 improved the protection against ionizing radiation by at least 1.93-fold and the repair frequency by 6.1-fold. In addition, our results show that homology length influences repair efficiency in rad52 mutant cells, which impacts BRCA2 mediated repair of DSBs. This study provides evidence that S. cerevisiae could be used to monitor BRCA2 function, which can help in understanding the genetic consequences of BRCA2 variants and how they may contribute to cancer progression.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":" ","pages":"301-308"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479210","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}
Current GeneticsPub Date : 2023-12-01Epub Date: 2023-05-10DOI: 10.1007/s00294-023-01270-6
Alexey P Galkin, Evgeniy I Sysoev, Anna A Valina
{"title":"Amyloids and prions in the light of evolution.","authors":"Alexey P Galkin, Evgeniy I Sysoev, Anna A Valina","doi":"10.1007/s00294-023-01270-6","DOIUrl":"10.1007/s00294-023-01270-6","url":null,"abstract":"<p><p>Functional amyloids have been identified in a wide variety of organisms including bacteria, fungi, plants, and vertebrates. Intracellular and extracellular amyloid fibrils of different proteins perform storage, protective, structural, and regulatory functions. The structural organization of amyloid fibrils determines their unique physical and biochemical properties. The formation of these fibrillar structures can provide adaptive advantages that are picked up by natural selection. Despite the great interest in functional and pathological amyloids, questions about the conservatism of the amyloid properties of proteins and the regularities in the appearance of these fibrillar structures in evolution remain almost unexplored. Using bioinformatics approaches and summarizing the data published previously, we have shown that amyloid fibrils performing similar functions in different organisms have been arising repeatedly and independently in the course of evolution. On the other hand, we show that the amyloid properties of a number of bacterial and eukaryotic proteins are evolutionarily conserved. We also discuss the role of protein-based inheritance in the evolution of microorganisms. Considering that missense mutations and the emergence of prions cause the same consequences, we propose the concept that the formation of prions, similarly to mutations, generally causes a negative effect, although it can also lead to adaptations in rare cases. In general, our analysis revealed certain patterns in the emergence and spread of amyloid fibrillar structures in the course of evolution.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":" ","pages":"189-202"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9443067","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}
Current GeneticsPub Date : 2023-12-01Epub Date: 2023-06-02DOI: 10.1007/s12070-023-03902-2
Soheil Mansour Sohani, Mehdi Akbari, Morteza Hamidi Nahrani
{"title":"Romberg Neck Torsion :A New Specific Test for Cervicogenic Dizziness.","authors":"Soheil Mansour Sohani, Mehdi Akbari, Morteza Hamidi Nahrani","doi":"10.1007/s12070-023-03902-2","DOIUrl":"10.1007/s12070-023-03902-2","url":null,"abstract":"<p><strong>Aims: </strong>Previous studies have shown that Cervical myofascial pain syndrome with dizziness (CMPS-D ) is one of the most common causes of cervicogenic dizziness and is associated with challenge in diagnosis and treatment. this study aimed to investigate the Romberg neck torsion test in patients with CMPS-D and healthy controls.</p><p><strong>Materials and methods: </strong>Cross-sectional, observational study. twenty patients with CMPS-D were compared with twenty healthy controls. the Romberg (neutral position and neck torsion) and smooth pursuit neck torsion tests were performed in patients with CMPS-D and healthy controls.</p><p><strong>Results: </strong>The results confirmed that there are significant differences in the Romberg neck torsion test between subjects with CMPS-D and healthy controls (<i>p</i> < 0.05). in addition, There was a significant correlation between Romberg neck torsion and smooth pursuit neck torsion results (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>The results of Romberg neck torsion test in CMPS-D subjects were different from those in healthy controls, which was attributed to neck pain and changes in cervical proprioception input. Romberg neck torsion is a new method for assessing cervicogenic dizziness.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":"11 1","pages":"2960-2965"},"PeriodicalIF":1.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72764467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current GeneticsPub Date : 2023-06-01DOI: 10.1007/s00294-023-01269-z
Mª Luz Muñoz-Megías, Ruth Sánchez-Fresneda, Francisco Solano, Sergi Maicas, María Martínez-Esparza, Juan-Carlos Argüelles
{"title":"The antifungal effect induced by itraconazole in Candida parapsilosis largely depends on the oxidative stress generated at the mitochondria.","authors":"Mª Luz Muñoz-Megías, Ruth Sánchez-Fresneda, Francisco Solano, Sergi Maicas, María Martínez-Esparza, Juan-Carlos Argüelles","doi":"10.1007/s00294-023-01269-z","DOIUrl":"https://doi.org/10.1007/s00294-023-01269-z","url":null,"abstract":"<p><p>In Candida parapsilosis, homozygous disruption of the two genes encoding trehalase activity increased the susceptibility to Itraconazole compared with the isogenic parental strain. The fungicidal effect of this azole can largely be counteracted by preincubating growing cells with rotenone and the protonophore 2,4-Dinitrophenol. In turn, measurement of endogenous reactive oxygen species formation by flow cytometry confirmed that Itraconazole clearly induced an internal oxidative stress, which can be significantly abolished in rotenone-exposed cells. Analysis of the antioxidant enzymatic activities of catalase and superoxide dismutase pointed to a moderate decrease of catalase in trehalase-deficient mutant cells compared to the wild type, with an additional increase upon addition of rotenone. These enzymatic changes were imperceptible in the case of superoxide dismutase. Alternative assays with Voriconazole led to a similar profile in the results regarding cell growth and antioxidant activities. Collectively, our data suggest that the antifungal action of Itraconazole on C. parapsilosis is dependent on a functional mitochondrial activity. They also suggest that the central metabolic pathways in pathogenic fungi should be considered as preferential antifungal targets in new research.</p>","PeriodicalId":10918,"journal":{"name":"Current Genetics","volume":"69 2-3","pages":"165-173"},"PeriodicalIF":2.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}