Biochimie最新文献

{"title":"Microscopic and metabolomics analysis of the anti-Listeria activity of natural and engineered cruzioseptins","authors":"Sebastián Bermúdez-Puga ,&nbsp;Meriellen Dias ,&nbsp;Iara Lima Reis ,&nbsp;Taciana Freire de Oliveira ,&nbsp;Sonia Regina Yokomizo de Almeida ,&nbsp;Maria Anita Mendes ,&nbsp;Simon J. Moore ,&nbsp;José R. Almeida ,&nbsp;Carolina Proaño-Bolaños ,&nbsp;Ricardo Pinheiro de Souza Oliveira","doi":"10.1016/j.biochi.2024.05.022","DOIUrl":"10.1016/j.biochi.2024.05.022","url":null,"abstract":"<div><p><em>Listeria monocytogenes</em> is a human opportunistic foodborne pathogen that produces life-threatening infections with a high mortality rate. The control of Listeria in the food production environment and effective clinical management of human listeriosis are challenging due to the emergence of antibiotic resistance. Hence we evaluate the <em>in vitro</em> anti-Listeria activity of two synthetic cruzioseptins reproducing their natural sequences CZS-9, and CZS-12, and one engineered sequence based on CZS-1, named [K4K15]CZS-1. The assessment of the <em>in vitro</em> potential of cruzioseptins, highlighted the promising antibacterial effect of [K4K15]CZS-1 in very low concentrations (0.91 μM) and its thermal stability at high-temperature conditions, is compatible with the food industry. Microscopic and metabolomic analyses suggest cruzioseptin induces anti-<em>Listeria</em> bioactivity through membrane disruption and changes in the intracellular metabolome. We also report that [K4K15]CZS-1 is not resistant to peptidases/proteases emphasizing a key advantage for their use as a food preservative. However, there is a need for further structural and functional optimisations for the potential clinical application as an antibiotic. In conclusion, [K4K15]CZS-1 stand out as membrane-active peptides with the ability to induce shifts in the bacteria metabolome and inspire the development of strategies for the prevention of <em>L. monocytogenes</em> emergence and dissemination.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heavy metal ions interactions with G-quadruplex-prone DNA sequences","authors":"Seyyed-Ali Mehrdad ,&nbsp;Anne Cucchiarini ,&nbsp;Jean-Louis Mergny ,&nbsp;Sakineh Kazemi Noureini","doi":"10.1016/j.biochi.2024.05.021","DOIUrl":"10.1016/j.biochi.2024.05.021","url":null,"abstract":"<div><p>The industrial world exposes living organisms to a variety of metal pollutants. Here we investigated whether such elements affect G-rich sequences susceptible to fold into G-quadruplex (GQ) structures. Thermal stability and conformation of these oligoncleotides was studied at various molar ratios of a variety of heavy metal salts using thermal FRET, transition-FRET (t-FRET) and circular dichroism. Metal ions affected the thermal stability of the GQs to different extents; some metals had no effect on T_m while other metals caused small to moderate changes in T_m at 1:1 or 1:10 molar ratio. While most of the metals had no major effect, Al³⁺, Cd²⁺, Pb²⁺, Hg²⁺ and Zn²⁺ altered the thermal stability and structural features of the GQs. Some metals such as Pb²⁺ and Hg²⁺ exhibit differential interactions with telomere, c-myc and c-kit GQs. Overall, toxic heavy metals affect G-quadruplex stability in a sequence and topology dependent manner. This study provides new insight into how heavy metal exposure may affect gene expression and cellular responses.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The antibacterial activity and mechanisms of Trp-containing peptides against multidrug-resistant Pseudomonas aeruginosa persisters","authors":"Mengmiao Li ,&nbsp;Xiaomi Sun ,&nbsp;Lei Zhao ,&nbsp;Wanying Du ,&nbsp;Dejing Shang","doi":"10.1016/j.biochi.2024.05.019","DOIUrl":"10.1016/j.biochi.2024.05.019","url":null,"abstract":"<div><p>Bacterial persisters avoid antibiotic-mediated death by entering a dormant state and are considered a major cause of antibiotic treatment failure. Antimicrobial peptides (AMPs) with membrane-disrupting activity are promising drugs to eradicate persister cells. In this study, carbonyl cyanide m-chlorophenylhydrazone (CCCP), ciprofloxacin (CIP), and rifampicin (RFP) were applied to induce the formation of multidrug-resistant <em>Pseudomonas aeruginosa</em> (MRPA0108) persisters, and the antibacterial activity and mechanisms of I1W and L12W (two Trp-containing peptides designed in our lab) against MRPA0108 persisters were investigated. The results showed that I1W and L12W displayed potent antibacterial activity against MRPA0108 persisters. Both Trp-containing peptides disturbed the inner and outer membrane of MRPA0108 persisters. In addition, I1W and L12W revealed novel antibacterial mechanisms by decreasing the enzymatic activities of superoxide dismutase (SOD) and catalase (CAT), increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, consequently leading to oxidative stress. The transcriptome profile of I1W-treated MRPA0108 persisters revealed that the genes involved in carbon metabolism, biosynthesis of amino acids, and the TCA cycle were downregulated, indicating that I1W interfered with metabolism and energy synthesis processes. Furthermore, both Trp-containing peptides displayed synergistic activities with antibiotic tobramycin and showed additive activities with cefepime or ciprofloxacin, which revealed a potential therapeutic strategy for the eradication of MRPA0108 persisters.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-induced downregulation of RNA m6A protein machinery in the naked mole-rat heart","authors":"W. Aline Ingelson-Filpula ,&nbsp;Karen L. Kadamani ,&nbsp;Mohammad Ojaghi ,&nbsp;Matthew E. Pamenter ,&nbsp;Kenneth B. Storey","doi":"10.1016/j.biochi.2024.05.017","DOIUrl":"10.1016/j.biochi.2024.05.017","url":null,"abstract":"<div><p>Naked mole-rats, <em>Heterocephalus glaber</em>, are champion hypoxia-tolerant rodents that live under low oxygen conditions in their subterranean burrows. Detrimental effects of low oxygen can be mitigated through metabolic rate depression (MRD), metabolic reorganization, and global downregulation of nonessential cellular processes. Recent research has progressively implicated epigenetic modifications – rapid, reversible changes to gene expression that do not alter the DNA sequence itself – as major players in implementing and maintaining MRD. N⁶-adenosine (m⁶A) methylation is the most prevalent mammalian RNA modification and is responsible for pre-mRNA processing and mRNA export from the nucleus. Hence, m⁶A -mediated conformational changes alter the cellular fate of transcripts. The present study investigated the role of m⁶A RNA methylation responses to 24 h of hypoxia exposure in <em>H. glaber</em> cardiac tissue. Total protein levels of m⁶A writers/readers/erasers, m⁶A demethylase activity, and total m⁶A quantification were measured under normoxic vs. hypoxic conditions in <em>H. glaber</em> heart. While there was no change in either demethylase activity or total m⁶A content, many proteins of the m⁶A pathway were downregulated during hypoxia. Overall, m⁶A may not be a signature hypoxia-responsive characteristic in <em>H. glaber</em> heart, but downregulation of the protein machinery involved in m⁶A cycling points to an alternate biological involvement. Further research will explore other forms of RNA modifications and other epigenetic mechanisms to determine the controls on hypoxia endurance in this subterranean mammal.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424001196/pdfft?md5=e4516dd4a25e746db6a4198b7ec50cc9&pid=1-s2.0-S0300908424001196-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-based drug design for TSPO: Challenges and opportunities","authors":"","doi":"10.1016/j.biochi.2024.05.018","DOIUrl":"10.1016/j.biochi.2024.05.018","url":null,"abstract":"<div><p>The translocator protein 18 kDa (TSPO) is an evolutionarily conserved mitochondrial transmembrane protein implicated in various neuropathologies and inflammatory conditions, making it a longstanding diagnostic and therapeutic target of interest. Despite the development of various classes of TSPO ligand chemotypes, and the elucidation of bacterial and non-human mammalian experimental structures, many unknowns exist surrounding its differential structural and functional features in health and disease. There are several limitations associated with currently used computational methodologies for modelling the native structure and ligand-binding behaviour of this enigmatic protein. In this perspective, we provide a critical analysis of the developments in the uses of these methods, outlining their uses, inherent limitations, and continuing challenges. We offer suggestions of unexplored opportunities that exist in the use of computational methodologies which offer promise for enhancing our understanding of the TSPO.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424001202/pdfft?md5=5861fa0167f6689f46ed0ac5bc6ac94d&pid=1-s2.0-S0300908424001202-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inside front cover-EDB","authors":"","doi":"10.1016/S0300-9084(24)00109-3","DOIUrl":"https://doi.org/10.1016/S0300-9084(24)00109-3","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424001093/pdfft?md5=f3e0bfe0b632556a31ed361b72f9347c&pid=1-s2.0-S0300908424001093-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A site-specific phosphorylation in FSTL1 determines its promigratory role in wound healing","authors":"Anagha Priya Suresh ,&nbsp;Monisha Vijayarengan ,&nbsp;Pooja Aggarwal ,&nbsp;Rajendran Soundaram ,&nbsp;B.S. Gnanesh Kumar ,&nbsp;Gopinath M. Sundaram","doi":"10.1016/j.biochi.2024.05.016","DOIUrl":"10.1016/j.biochi.2024.05.016","url":null,"abstract":"<div><p>Follistatin like-1 (FSTL-1) is a secreted glycoprotein of mesenchymal in origin. In human skin, FSTL1 is upregulated in the epidermal keratinocytes upon acute injury and is required for the migration of keratinocytes. Failure to upregulate FSTL1 leads to the lack of keratinocyte migration and the non-healing nature of diabetic foot ulcer (DFU). FSTL1 undergoes extensive post-translational modification (PTM) at specific residues. Glycosylation at N144, N175 and N180, are the only experimentally demonstrated PTM in FSTL1, wherein, N180 and N144 glycosylations have been found to be critical for its function in cardiac tissue regeneration and pre-adipocyte differentiation, respectively. However, it is not known if PTMs other than glycosylation occurs in FSTL1 and how it impacts its pro-migratory function. Using <em>in-silico</em> analysis of mass spectrometric datasets, we found a novel PTM, namely, Serine 165 (S165) phosphorylation in FSTL1. To address the role of S165 phosphorylation in its pro-migratory function, a phosphorylation defective mutant of FSTL1 (S165A) was constructed by converting serine 165 to alanine and over expressed in 293T cells. S165A mutation did not affect the secretion of FSTL1 <em>in vitro</em>. However, S165A abolished the pro-migratory effect of FSTL1 in cultured keratinocytes likely <em>via</em> its inability to facilitate ERK signaling pathway. Interestingly, bacterially expressed recombinant FSTL1, <em>trans</em>-dominantly inhibited wound closure in keratinocytes highlighting the prime role of FSTL1 phosphorylation for its pro-migratory function. Further, under high glucose conditions, which inhibited scratchwound migration of keratinocytes, we noticed a significant decrease in S165 phosphorylation. Taken together, our results reveal a hitherto unreported role of FSTL1 phosphorylation PTM with profound implications in wound healing.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring venom diversity in Mixcoatlus browni and Mixcoatlus barbouri: A comparative analysis of two rare Mexican snake species with crotoxin-like presence","authors":"Edgar Neri-Castro ,&nbsp;Vanessa Zarzosa ,&nbsp;Bruno Lomonte ,&nbsp;Fernando Zamudio ,&nbsp;Lorena Hernandez-Orihuela ,&nbsp;Alejandro Olvera-Rodríguez ,&nbsp;Audrey Michelle Rodríguez-Solís ,&nbsp;Miguel Borja ,&nbsp;Uri O. García-Vázquez ,&nbsp;Jason M. Jones ,&nbsp;Chistopher L. Parkinson ,&nbsp;Alejandro Alagón","doi":"10.1016/j.biochi.2024.05.015","DOIUrl":"10.1016/j.biochi.2024.05.015","url":null,"abstract":"<div><p>The genus <em>Mixcoatlus</em> is composed of three species: <em>Mixcoatlus barbouri</em>, <em>M. browni</em>, and <em>M. melanurus</em>, of which the venom composition of <em>M. melanurus</em>, the most common species of the three, has only recently been described. However, very little is known about the natural history of <em>M. barbouri</em> and <em>M. browni</em>, and the venom composition of these two species has remained thus far unexplored. In this study we characterize the proteomic profiles and the main biochemical and toxic activities of these two venoms. Proteomic data obtained by shotgun analysis of whole venom identified 12 protein families for <em>M. barbouri</em>, and 13 for <em>M</em>. <em>browni</em>. The latter venom was further characterized by using a quantitative ‘venomics’ protocol, which revealed that it is mainly composed of 51.1 % phospholipases A₂ (PLA₂), 25.5 % snake venom serine proteases (SVSP), 4.6 % <span>l</span>-amino oxidases (LAO), and 3.6 % snake venom metalloproteases (SVMP), with lower percentages other six protein families. Both venoms contained homologs of the basic and acidic subunits of crotoxin. However, due to limitations in <em>M. barbouri</em> venom availability, we could only characterize the crotoxin-like protein of <em>M. browni</em> venom, which we have named Mixcoatlutoxin. It exhibited a lethal potency in mice like that described for classical rattlesnake crotoxins. These findings expand knowledge on the distribution of crotoxin-like heterodimeric proteins in viper snake species. Further investigation of the bioactivities of the venom of <em>M. barbouri</em>, on the other hand, remains necessary.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly specific aptamer trap for extremophilic RNA polymerases","authors":"Ivan Petushkov ,&nbsp;Andrey Feklistov ,&nbsp;Andrey Kulbachinskiy","doi":"10.1016/j.biochi.2024.05.014","DOIUrl":"10.1016/j.biochi.2024.05.014","url":null,"abstract":"<div><p>During transcription initiation, the holoenzyme of bacterial RNA polymerase (RNAP) specifically recognizes promoters using a dedicated σ factor. During transcription elongation, the core enzyme of RNAP interacts with nucleic acids mainly nonspecifically, by stably locking the DNA template and RNA transcript inside the main cleft. Here, we present a synthetic DNA aptamer that is specifically recognized by both core and holoenzyme RNAPs from extremophilic bacteria of the <em>Deinococcus-Thermus</em> phylum. The aptamer binds RNAP with subnanomolar affinities, forming extremely stable complexes even at high ionic strength conditions, blocks RNAP interactions with the DNA template and inhibits RNAP activity during transcription elongation. We propose that the aptamer binds at a conserved site within the downstream DNA-binding cleft of RNAP and traps it in an inactive conformation. The aptamer can potentially be used for structural studies to reveal RNAP conformational states, affinity binding of RNAP and associated factors, and screening of transcriptional inhibitors.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141047561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico evidence that substitution of glycine for valine (p.G8V) in a common variant of TMPRSS2 isoform 1 increases accessibility to an endocytic signal: Implication for SARS-cov-2 entry into host cells and susceptibility to COVID-19","authors":"Matteo Calcagnile ,&nbsp;Fabrizio Damiano ,&nbsp;Giambattista Lobreglio ,&nbsp;Luisa Siculella ,&nbsp;Maria Pia Bozzetti ,&nbsp;Patricia Forgez ,&nbsp;Alexandra Malgoyre ,&nbsp;Nicolas Libert ,&nbsp;Cecilia Bucci ,&nbsp;Marco Alifano ,&nbsp;Pietro Alifano","doi":"10.1016/j.biochi.2024.05.004","DOIUrl":"10.1016/j.biochi.2024.05.004","url":null,"abstract":"<div><p>The TMPRSS2 protease plays a key role in the entry of the SARS-CoV-2 into cells. The <em>TMPRSS2</em> gene is highly polymorphic in humans, and some polymorphisms may affect the susceptibility to COVID-19 or disease severity. rs75603675 (c.23G &gt; T) is a missense variant that causes the replacement of glycine with valine at position 8 (p.G8V) in the TMPRSS2 isoform 1. According to GnomAD v4.0.0 database, the allele frequency of the rs75603675 on a global scale is 38.10 %, and range from 0.92 % in East Asian to 40.77 % in non-Finnish European (NFE) population. We analyzed the occurrence of the rs75603675 in two cohorts of patients, the first with severe/critical COVID-19 enrolled in a French hospital (42 patients), and the second with predominantly asymptomatic/pauci-symptomatic/mild COVID-19 enrolled in an Italian hospital (69 patients). We found that the <em>TMPRSS2</em>-c.23T minor allele frequency was similar in the two cohorts, 46.43 % and 46.38 %, respectively, and higher than the frequency in the NFE population (40.77 %). Chi-square test provided significant results (p &lt; 0.05) when the genotype data (<em>TMPRSS2</em>-c.23T/c.23T homozygotes + <em>TMPRSS2</em>-c.23G/c.23T heterozygotes vs. <em>TMPRSS2</em>-c.23G/c.23G homozygotes) of the two patient groups were pooled and compared to the expected data for the NFE population, suggesting a possible pathogenetic mechanism of the p.G8V substitution. We explored the possible effects of the p.G8V substitution and found that the N-terminal region of the TMPRSS2 isoform 1 contains a signal for clathrin/AP-2-dependent endocytosis. <em>In silico</em> analysis predicted that the p.G8V substitution may increase the accessibility to the endocytic signal, which could help SARS-CoV-2 enter cells.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}