Microbial Cell最新文献

{"title":"Basal level of ppGpp coordinates <i>Escherichia coli</i> cell heterogeneity and ampicillin resistance and persistence.","authors":"Paulina Katarzyna Grucela, Yong Everett Zhang","doi":"10.15698/mic2023.11.808","DOIUrl":"https://doi.org/10.15698/mic2023.11.808","url":null,"abstract":"<p><p>The universal stringent response alarmone ppGpp (guanosine penta and tetra phosphates) plays a crucial role in various aspects of fundamental cell physiology (e.g., cell growth rate, cell size) and thus bacterial tolerance to and survival of external stresses, including antibiotics. Besides transient antibiotic tolerance (persistence), ppGpp was recently found to contribute to <i>E. coli</i> resistance to ampicillin. How ppGpp regulates both the persistence and resistance to antibiotics remains incompletely understood. In this study, we first clarified that the absence of ppGpp in <i>E. coli</i> (ppGpp⁰ strain) resulted in a decreased minimal inhibition concentration (MIC) value of ampicillin but, surprisingly, a higher persistence level to ampicillin during exponential growth in MOPS rich medium. High basal ppGpp levels, thus lower growth rate, did not produce high ampicillin persistence. Importantly, we found that the high ampicillin persistence of the ppGpp⁰ strain is not due to dormant overnight carry-over cells. Instead, the absence of ppGpp produced higher cell heterogeneity, propagating during the regrowth and the killing phases, leading to higher ampicillin persistence. Consistently, we isolated a suppressor mutation of the ppGpp⁰ strain that restored the standard MIC value of ampicillin and reduced its cell heterogeneity and the ampicillin persistence level concomitantly. Altogether, we discussed the fundamental role of basal level of ppGpp in regulating cell homogeneity and ampicillin persistence.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"10 11","pages":"248-260"},"PeriodicalIF":4.6,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483283","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":"Phospholipases A and Lysophospholipases in protozoan parasites.","authors":"Perrine Hervé,&nbsp;Sarah Monic,&nbsp;Frédéric Bringaud,&nbsp;Loïc Rivière","doi":"10.15698/mic2023.10.805","DOIUrl":"https://doi.org/10.15698/mic2023.10.805","url":null,"abstract":"Phospholipases (PLs) and Lysophospholipases (LysoPLs) are a diverse group of esterases responsible for phospholipid or lysophospholipid hydrolysis. They are involved in several biological processes, including lipid catabolism, modulation of the immune response and membrane maintenance. PLs are classified depending on their site of hydrolysis as PLA1, PLA2, PLC and PLD. In many pathogenic microorganisms, from bacteria to fungi, PLAs and LysoPLs have been described as critical virulence and/or pathogenicity factors. In protozoan parasites, a group containing major human and animal pathogens, growing literature show that PLAs and LysoPLs are also involved in the host infection. Their ubiquitous presence and role in host-pathogen interactions make them particularly interesting to study. In this review, we summarize the literature on PLAs and LysoPLs in several protozoan parasites of medical relevance, and discuss the growing interest for them as potential drug and vaccine targets.","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"10 10","pages":"204-216"},"PeriodicalIF":4.6,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134890","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":"Biofilm tolerance, resistance and infections increasing threat of public health.","authors":"Shanshan Yang, Xinfei Li, Weihe Cang, Delun Mu, Shuaiqi Ji, Yuejia An, Rina Wu, Junrui Wu","doi":"10.15698/mic2023.11.807","DOIUrl":"https://doi.org/10.15698/mic2023.11.807","url":null,"abstract":"<p><p>Microbial biofilms can cause chronic infection. In the clinical setting, the biofilm-related infections usually persist and reoccur; the main reason is the increased antibiotic resistance of biofilms. Traditional antibiotic therapy is not effective and might increase the threat of antibiotic resistance to public health. Therefore, it is urgent to study the tolerance and resistance mechanism of biofilms to antibiotics and find effective therapies for biofilm-related infections. The tolerance mechanism and host reaction of biofilm to antibiotics are reviewed, and bacterial biofilm related diseases formed by human pathogens are discussed thoroughly. The review also explored the role of biofilms in the development of bacterial resistance mechanisms and proposed therapeutic intervention strategies for biofilm related diseases.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"10 11","pages":"233-247"},"PeriodicalIF":4.6,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483284","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":"Investigation of the acetic acid stress response in <i>Saccharomyces cerevisiae</i> with mutated H3 residues.","authors":"Nitu Saha,&nbsp;Swati Swagatika,&nbsp;Raghuvir Singh Tomar","doi":"10.15698/mic2023.10.806","DOIUrl":"https://doi.org/10.15698/mic2023.10.806","url":null,"abstract":"<p><p>Enhanced levels of acetic acid reduce the activity of yeast strains employed for industrial fermentation-based applications. Therefore, unraveling the genetic factors underlying the regulation of the tolerance and sensitivity of yeast towards acetic acid is imperative for optimising various industrial processes. In this communication, we have attempted to decipher the acetic acid stress response of the previously reported acetic acid-sensitive histone mutants. Revalidation using spot-test assays and growth curves revealed that five of these mutants, viz., H3K18Q, H3S28A, H3K42Q, H3Q68A, and H3F104A, are most sensitive towards the tested acetic acid concentrations. These mutants demonstrated enhanced acetic acid stress response as evidenced by the increased expression levels of <i>AIF1</i>, reactive oxygen species (ROS) generation, chromatin fragmentation, and aggregated actin cytoskeleton. Additionally, the mutants exhibited active cell wall damage response upon acetic acid treatment, as demonstrated by increased Slt2-phosphorylation and expression of cell wall integrity genes. Interestingly, the mutants demonstrated increased sensitivity to cell wall stress-causing agents. Finally, screening of histone H3 N-terminal tail truncation mutants revealed that the tail truncations exhibit general sensitivity to acetic acid stress. Some of these N-terminal tail truncation mutants viz., H3 [del 1-24], H3 [del 1-28], H3 [del 9-24], and H3 [del 25-36] are also sensitive to cell wall stress agents such as Congo red and caffeine suggesting that their enhanced acetic acid sensitivity may be due to cell wall stress induced by acetic acid.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"10 10","pages":"217-232"},"PeriodicalIF":4.6,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125994","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":"Multiple genome analysis of <i>Candida glabrata</i> clinical isolates renders new insights into genetic diversity and drug resistance determinants.","authors":"Pedro Pais,&nbsp;Mónica Galocha,&nbsp;Azusa Takahashi-Nakaguchi,&nbsp;Hiroji Chibana,&nbsp;Miguel C Teixeira","doi":"10.15698/mic2022.11.786","DOIUrl":"https://doi.org/10.15698/mic2022.11.786","url":null,"abstract":"<p><p>The emergence of drug resistance significantly hampers the treatment of human infections, including those caused by fungal pathogens such as <i>Candida</i> species. <i>Candida glabrata</i> ranks as the second most common cause of candidiasis worldwide, supported by rapid acquisition of resistance to azole and echinocandin antifungals frequently prompted by single nucleotide polymorphisms (SNPs) in resistance associated genes, such as <i>PDR1</i> (azole resistance) or <i>FKS1/2</i> (echinocandin resistance). To determine the frequency of polymorphisms and genome rearrangements as the possible genetic basis of <i>C. glabrata</i> drug resistance, we assessed genomic variation across 94 globally distributed isolates with distinct resistance phenotypes, whose sequence is deposited in GenBank. The genomes of three additional clinical isolates were sequenced, in this study, including two azole resistant strains that did not display Gain-Of-Function (GOF) mutations in the transcription factor encoding gene <i>PDR1</i>. Genomic variations in susceptible isolates were used to screen out variants arising from genome diversity and to identify variants exclusive to resistant isolates. More than half of the azole or echinocandin resistant isolates do not possess exclusive polymorphisms in <i>PDR1</i> or <i>FKS1/2</i>, respectively, providing evidence of alternative genetic basis of antifungal resistance. We also identified copy number variations consistently affecting a subset of chromosomes. Overall, our analysis of the genomic and phenotypic variation across isolates allowed to pinpoint, in a genome-wide scale, genetic changes enriched specifically in antifungal resistant strains, which provides a first step to identify additional determinants of antifungal resistance. Specifically, regarding the newly sequenced strains, a set of mutations/genes are proposed to underlie the observed unconventional azole resistance phenotype.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 11","pages":"174-189"},"PeriodicalIF":4.6,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40489690","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":"Flagellated bacterial porter for <i>in situ</i> tumor vaccine.","authors":"Haiheng Xu,&nbsp;Yiqiao Hu,&nbsp;Jinhui Wu","doi":"10.15698/mic2022.09.784","DOIUrl":"https://doi.org/10.15698/mic2022.09.784","url":null,"abstract":"<p><p>Cancer immunotherapy, which use the own immune system to attack tumors, are increasingly popular treatments. But, due to the tumor immunosuppressive microenvironment, the antigen presentation in the tumor is limited. Recently, a growing number of people use bacteria to stimulate the body's immunity for tumor treatment due to bacteria themselves have a variety of elements that activate Toll-like receptors. Here, we discuss the use of motility of flagellate bacteria to transport antigens to the tumor periphery to activate peritumoral dendritic cells to enhance the effect of <i>in situ</i> tumor vaccines.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 9","pages":"158-161"},"PeriodicalIF":4.6,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9442148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40369855","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":"The rise of <i>Candida auris</i>: from unique traits to co-infection potential.","authors":"Nadine B Egger, Katharina Kainz, Adina Schulze, Maria A Bauer, Frank Madeo, Didac Carmona-Gutierrez","doi":"10.15698/mic2022.08.782","DOIUrl":"10.15698/mic2022.08.782","url":null,"abstract":"<p><p><i>Candida auris</i> is a multidrug resistant (MDR) fungal pathogen with a crude mortality rate of 30-60%. First identified in 2009, <i>C. auris</i> has been rapidly emerging to become a global risk in clinical settings and was declared an urgent health threat by the Centers for Disease Control and Prevention (CDC). A concerted global action is thus needed to successfully tackle the challenges created by this emerging fungal pathogen. In this brief article, we underline the importance of unique virulence traits,including its easy transformation, its persistence outside the host and its resilience against multiple cellular stresses, as well as of environmental factors that have mainly contributed to the rise of this superbug.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 8","pages":"141-144"},"PeriodicalIF":4.1,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40619125","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":"Swimming faster despite obstacles: a universal mechanism behind bacterial speed enhancement in complex fluids.","authors":"Shashank Kamdar,&nbsp;Xiang Cheng","doi":"10.15698/mic2022.07.781","DOIUrl":"https://doi.org/10.15698/mic2022.07.781","url":null,"abstract":"<p><p>Bacteria constitute about 15% of global biomass and their natural environments often contain polymers and colloids, which show complex flow behaviors. It is crucial to study their motion in such environments to understand their growth and spreading as well as to design synthetic microswimmers for biomedical applications. Bacterial motion in complex viscous environments, although extensively studied over the past six decades, still remains poorly understood. In our recent study combining experimental data and theoretical analysis, we found a surprising similarity between bacterial motion in dilute colloidal suspensions and polymer solutions, which challenged the established view on the role of polymer dynamics on bacterial speed enhancement. We subsequently developed a physical model that provides a universal mechanism explaining bacterial speed enhancement in complex fluids.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 7","pages":"139-140"},"PeriodicalIF":4.6,"publicationDate":"2022-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40606428","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 roadmap for designing narrow-spectrum antibiotics targeting bacterial pathogens.","authors":"Xinyun Cao,&nbsp;Robert Landick,&nbsp;Elizabeth A Campbell","doi":"10.15698/mic2022.07.780","DOIUrl":"https://doi.org/10.15698/mic2022.07.780","url":null,"abstract":"<p><p><i>Clostridioides difficile</i> (<i>Cdiff</i>) infection (CDI) continues to be the leading threat of nosocomial deaths worldwide and a major burden on health-care systems. Broad-spectrum antibiotics eradicate the normal gut microbiome, killing protective commensal bacteria and increasing CDI recurrence. In contrast, Fidaxomicin (Fdx) is a narrow-spectrum antibiotic that inhibits <i>Cdiff</i> growth without affecting crucial gut microbes. However, the basis of the narrow-spectrum activity of Fdx on its target, RNA polymerase (RNAP), in <i>Cdiff</i> has been enigmatic. Recently, Cao <i>et al.</i> (Nature, doi: 10.1038/s41586-022-04545-z) combined transgenic RNAP design and synthesis with cryo-electron microscopy (cryo-EM) to identify a key determinant of Fdx inhibition of <i>Cdiff</i> RNAP. This finding was further corroborated by biochemical, bioinformatics, and genetic analysis. This microreview describes implications of this work for lineage-specific antibiotic design and new directions toward understanding transcription and regulation in <i>Cdiff</i> and other bacterial pathogens.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 7","pages":"136-138"},"PeriodicalIF":4.6,"publicationDate":"2022-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40606427","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":"Breaking the clip for cargo unloading from motor proteins: mechanism and significance.","authors":"Keisuke Obara,&nbsp;Takumi Kamura","doi":"10.15698/mic2022.06.779","DOIUrl":"https://doi.org/10.15698/mic2022.06.779","url":null,"abstract":"<p><p>The mitochondrion is an essential organelle involved in ATP generation, lipid metabolism, regulation of calcium ions, etc. Therefore, it should be inherited properly by newly generated cells. In the budding yeast <i>Saccharomyces cerevisiae</i>, mitochondria are passed on to daughter cells by the motor protein, Myo2, on the actin cable. The mitochondria and Myo2 are connected via the adaptor protein Mmr1. After reaching daughter cells, mitochondria are released from the actin-myosin machinery and move dynamically. In our recent paper (Obara K <i>et al.</i> (2022), Nat Commun, doi:10.1038/s41467-022-29704-8), we demonstrated that the regulated proteolysis of Mmr1 is required for the unloading of mitochondria from Myo2 in daughter cells. Sequential post-translational modifications of Mmr1, <i>i.e.,</i> phosphorylation followed by ubiquitination, are essential for Mmr1 degradation and mitochondrial release from Myo2. Defects in Mmr1 degradation cause stacking and deformation of mitochondria at the bud-tip and bud-neck, where Myo2 accumulates. Compared to wild-type cells, mutant cells with defects in Mmr1 degradation possess an elevated mitochondrial membrane potential and produce higher levels of reactive oxygen species (ROS), along with hypersensitivity to oxidative stress.</p>","PeriodicalId":18397,"journal":{"name":"Microbial Cell","volume":"9 6","pages":"133-135"},"PeriodicalIF":4.6,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9173699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40487328","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}