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Articles 1 - 30 of 90
Full-Text Articles in Life Sciences
Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah
Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah
Theses
Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …
Effects Of Climate Change On Human Health, Sara El Houzaly, Richa Gupta
Effects Of Climate Change On Human Health, Sara El Houzaly, Richa Gupta
Publications and Research
The effects of climate change are evident worldwide as average global land and air temperatures have been rising, glaciers and ice sheets are shrinking with the concomitant rise in sea levels, extreme weather events have become more frequent, and oceans are warming and acidifying. Humanity is facing a big environmental challenge which not only impacts our habitat but will also have ramifications on our health. The present review describes a detailed examination of the scientific evidence proving the relationship between climate change and various fatal human diseases in different geographical regions. Our findings indicate that variations in the patterns of …
Single-Cell Approach Reveals Intercellular Heterogeneity In Phage-Producing Capacities, Sherin Kannoly, Gabriella Oken, Jonathan Shadan, David Musheyev, Kevin Singh, Abhyudai Singh, John J. Dennehy
Single-Cell Approach Reveals Intercellular Heterogeneity In Phage-Producing Capacities, Sherin Kannoly, Gabriella Oken, Jonathan Shadan, David Musheyev, Kevin Singh, Abhyudai Singh, John J. Dennehy
Publications and Research
Bacteriophage burst size is the average number of phage virions released from infected bacterial cells, and its magnitude depends on the duration of an intracellular progeny accumulation phase. Burst size is often measured at the population level, not the single-cell level, and consequently, statistical moments are not commonly available. In this study, we estimated the bacteriophage lambda (ƛ) single-cell burst size mean and variance following different intracellular accumulation period durations by employing Escherichia coli lysogens bearing lysis-deficient ƛ prophages. Single lysogens can be isolated and chemically lysed at desired times following prophage induction to quantify progeny intracellular accumulation within individual …
Novel Technologies To Characterize And Engineer The Microbiome In Inflammatory Bowel Disease, Alba Boix-Amorós, Hilarly Monaco, Elisa Sambataro, Jose C. Clemente
Novel Technologies To Characterize And Engineer The Microbiome In Inflammatory Bowel Disease, Alba Boix-Amorós, Hilarly Monaco, Elisa Sambataro, Jose C. Clemente
Publications and Research
We present an overview of recent experimental and computational advances in technology used to characterize the microbiome, with a focus on how these developments improve our understanding of inflammatory bowel disease (IBD). Specifically, we present studies that make use of flow cytometry and metabolomics assays to provide a functional characterization of microbial communities. We also describe computational methods for strain-level resolution, temporal series, myco - biome and virome data, co-occurrence networks, and compositional data analysis. In addition, we review novel techniques to therapeutically manipulate the microbiome in IBD. We discuss the benefits and drawbacks of these technologies to increase awareness …
Thrombospondin-1 Expression And Modulation Of Wnt And Hippo Signaling Pathways During The Early Phase Of Trypanosoma Cruzi Infection Of Heart Endothelial Cells, Ashutosh Arun, Kayla J. Rayford, Ayorinde Cooley, Tanu Rana, Girish Rachakonda, Fernando Villalta, Siddharth Pratap, Maria F. Lima, Nader Sheibani, Pius N. Nde
Thrombospondin-1 Expression And Modulation Of Wnt And Hippo Signaling Pathways During The Early Phase Of Trypanosoma Cruzi Infection Of Heart Endothelial Cells, Ashutosh Arun, Kayla J. Rayford, Ayorinde Cooley, Tanu Rana, Girish Rachakonda, Fernando Villalta, Siddharth Pratap, Maria F. Lima, Nader Sheibani, Pius N. Nde
Publications and Research
The protozoan parasite, Trypanosoma cruzi, causes severe morbidity and mortality in afflicted individuals. Approximately 30% of T. cruzi infected individuals present with cardiac pathology. The invasive forms of the parasite are carried in the vascular system to infect other cells of the body. During transportation, the molecular mechanisms by which the parasite signals and interact with host endothelial cells (EC) especially heart endothelium is currently unknown. The parasite increases host thrombospondin-1 (TSP1) expression and activates the Wnt/β-catenin and hippo signaling pathways during the early phase of infection. The links between TSP1 and activation of the signaling pathways and …
An Optimal Lysis Time Maximizes Bacteriophage Fitness In Quasi-Continuous Culture, Sherin Kannoly, Abhyudai Singh, John J. Dennehy
An Optimal Lysis Time Maximizes Bacteriophage Fitness In Quasi-Continuous Culture, Sherin Kannoly, Abhyudai Singh, John J. Dennehy
Publications and Research
Optimality models have a checkered history in evolutionary biology. While optimality models have been successful in providing valuable insight into the evolution of a wide variety of biological traits, a common objection is that optimality models are overly simplistic and ignore organismal genetics. We revisit evolutionary optimization in the context of a major bacteriophage life history trait, lysis time. Lysis time refers to the period spanning phage infection of a host cell and its lysis, whereupon phage progenies are released. Lysis time, therefore, directly determines phage fecundity assuming progeny assembly does not exhaust host resources prior to lysis. Noting that …
Tracking Cryptic Sars-Cov-2 Lineages Detected In Nyc Wastewater, Davida S. Smyth, Monica Trujillo, Devon A. Gregory, Kristen Cheung, Anna Gao, Maddie Graham, Yue Guan, Caitlyn Guldenpfennig, Irene Hoxie, Sherin Kannoly, Nanami Kubota, Terri D. Lyddon, Michelle Markman, Clayton Rushford, Kaung Myat San, Geena Sompanya, Fabrizio Spagnolo, Reinier Suarez, Emma Teixeiro, Mark Daniels, Marc C. Johnson, John J. Dennehy
Tracking Cryptic Sars-Cov-2 Lineages Detected In Nyc Wastewater, Davida S. Smyth, Monica Trujillo, Devon A. Gregory, Kristen Cheung, Anna Gao, Maddie Graham, Yue Guan, Caitlyn Guldenpfennig, Irene Hoxie, Sherin Kannoly, Nanami Kubota, Terri D. Lyddon, Michelle Markman, Clayton Rushford, Kaung Myat San, Geena Sompanya, Fabrizio Spagnolo, Reinier Suarez, Emma Teixeiro, Mark Daniels, Marc C. Johnson, John J. Dennehy
Publications and Research
Tracking SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may lead to the emergence of novel variants resistant to naturally acquired or vaccine-induced immunity. To monitor New York City (NYC) for the presence of novel variants, we deep sequence most of the receptor binding domain coding sequence of the S protein of SARS-CoV-2 isolated from the New York City wastewater. Here we report detecting increasing frequencies of novel cryptic SARS-CoV-2 lineages not recognized in GISAID’s EpiCoV database. These lineages contain mutations that had been rarely observed in clinical samples, including Q493K, Q498Y, E484A, and T572N and share many mutations …
High-Resolution Cryo-Electron Microscopy Structure Of Photosystem Ii From The Mesophilic Cyanobacterium, Synechocystis Sp. Pcc 6803, Christopher J. Gisriel, Jimin Wang, Jinchan Liu, David A. Flesher, Krystle M. Reiss, Hao-Li Huang, Ke R. Yang, William H. Armstrong, M. R. Gunner, Victor S. Batista, Richard J. Debus, Gary W. Brudvig
High-Resolution Cryo-Electron Microscopy Structure Of Photosystem Ii From The Mesophilic Cyanobacterium, Synechocystis Sp. Pcc 6803, Christopher J. Gisriel, Jimin Wang, Jinchan Liu, David A. Flesher, Krystle M. Reiss, Hao-Li Huang, Ke R. Yang, William H. Armstrong, M. R. Gunner, Victor S. Batista, Richard J. Debus, Gary W. Brudvig
Publications and Research
Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a highresolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the …
Type Vi Secretion System Mutations Reduced Competitive Fitness Of Classical Vibrio Cholerae Biotype, Benjamin Kostiuk, Francis J. Santoriello, Laura Diaz-Satizabal, Fabiana Bisaro, Kyung-Jo Lee, Anna N. Dhody, Daniele Provenzano, Daniel Unterweger, Stefan Pukatzki
Type Vi Secretion System Mutations Reduced Competitive Fitness Of Classical Vibrio Cholerae Biotype, Benjamin Kostiuk, Francis J. Santoriello, Laura Diaz-Satizabal, Fabiana Bisaro, Kyung-Jo Lee, Anna N. Dhody, Daniele Provenzano, Daniel Unterweger, Stefan Pukatzki
Publications and Research
The gram-negative bacterium Vibrio cholerae is the causative agent of the diarrhoeal disease cholera and is responsible for seven recorded pandemics. Several factors are postulated to have led to the decline of 6th pandemic classical strains and the rise of El Tor biotype V. cholerae, establishing the current 7th pandemic. We investigated the ability of classical V. cholerae of the 2nd and 6th pandemics to engage their type six secretion system (T6SS) in microbial competition against non-pandemic and 7th pandemic strains. We report that classical V. cholerae underwent sequential mutations in T6SS genetic determinants that initially exposed 2nd pandemic strains …
The Temperature-Dependent Conformational Ensemble Of Sars-Cov-2 Main Protease (Mpro), Ali Ebrahim, Blake T. Riley, Desigan Kumaran, Babak Andi, Martin R. Fuchs, Sean Mcsweeney, Daniel A. Keedy
The Temperature-Dependent Conformational Ensemble Of Sars-Cov-2 Main Protease (Mpro), Ali Ebrahim, Blake T. Riley, Desigan Kumaran, Babak Andi, Martin R. Fuchs, Sean Mcsweeney, Daniel A. Keedy
Publications and Research
The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or Mpro, is a promising target for development of novel antiviral therapeutics. Previous X-ray crystal structures of Mpro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded Mpro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these datasets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a temperature-dependent conformational landscape for Mpro, including …
A Conserved Structural Role For The Walker-A Lysine In P-Loop Containing Kinases, Fatlum Hajredini, Ranajeet Ghose
A Conserved Structural Role For The Walker-A Lysine In P-Loop Containing Kinases, Fatlum Hajredini, Ranajeet Ghose
Publications and Research
Bacterial tyrosine kinases (BY-kinases) and shikimate kinases (SKs) comprise two structurally divergent P-loop containing enzyme families that share similar catalytic site geometries, most notably with respect to their Walker-A, Walker-B, and DxD motifs. We had previously demonstrated that in BY-kinases, a specific interaction between the Walker-A and Walker-B motifs, driven by the conserved “catalytic” lysine housed on the former, leads to a conformation that is unable to efficiently coordinate Mg2+•ATP and is therefore incapable of chemistry. Here, using enhanced sampling molecular dynamics simulations, we demonstrate that structurally similar interactions between the Walker-A and Walker-B motifs, also mediated by …
Editorial: Pathogens, Pathobionts, And Autoimmunity, Linda A. Spatz, Gregg J. Silverman, Judith A. James
Editorial: Pathogens, Pathobionts, And Autoimmunity, Linda A. Spatz, Gregg J. Silverman, Judith A. James
Publications and Research
No abstract provided.
Don't Sell Them Short, There's More To Bacterial Natural Products Than Antibiotics, Alison Clare Domzalski
Don't Sell Them Short, There's More To Bacterial Natural Products Than Antibiotics, Alison Clare Domzalski
Dissertations, Theses, and Capstone Projects
Recent genomic studies of microbiomes have revealed an overwhelming number of biosynthetic genes of unknown function. Most of these “cryptic” biosynthetic genes are not expressed in laboratory monocultures of individual microbes. Thus, there remains tremendous untapped potential for natural products discovery. Here we employ mixed microbial culture (MMC) as a simple yet powerful approach to awaken cryptic biosynthetic gene clusters. Our preliminary studies demonstrated that arrays of metabolites could be induced in MMCs upon environmental cues, such as surface adhesion. Using this system, we have screened, identified, and isolated bioactive bacterial metabolites, which were characterized structurally and biologically. Of the …
Oxydifficidin-Producing Bacillus Presents Novel Antimicrobial Activity Against Neisseria Gonorrhoeae Involving The Deda Protein, Jingbo Kan
Dissertations, Theses, and Capstone Projects
Bacterial human pathogens cause severe infectious diseases which are the second most common cause of death next to cancer and cardiovascular diseases in the world, especially in developing countries. Gonorrhea particularly, is the second most common sexually transmitted infection (STI) which is caused by the microorganism Neisseria gonorrhoeae (GC). Centers for Disease Control and Prevention (CDC) estimates that more than 1.6 million new gonorrhea cases emerged in USA in 2018 (“Detailed STD Facts - Gonorrhea” n.d.). Also, the WHO (World Health Organization) shows that gonorrhea is the most antibiotic resistant STI (“PAHO/WHO | Gonorrhea” n.d.), highlighting the shortage of efficient …
You Are What You Eat — Exploring The Microbiome Through Inquiry-Based Labs. Microbiome Lesson Plans, Karla S. Fuller
You Are What You Eat — Exploring The Microbiome Through Inquiry-Based Labs. Microbiome Lesson Plans, Karla S. Fuller
Open Educational Resources
If these commonly used spices have the ability to inhibit pathogenic bacterial growth, could they also potentially inhibit the growth of normal, harmless bacteria that live in your body? In this lab, we will test common bacteria for resistance to food additives.
Telomeric And Sub-Telomeric Structure And Implications In Fungal Opportunistic Pathogens, Raffaella Diotti, Michelle Esposito, Chang Hui Shen
Telomeric And Sub-Telomeric Structure And Implications In Fungal Opportunistic Pathogens, Raffaella Diotti, Michelle Esposito, Chang Hui Shen
Publications and Research
Telomeres are long non-coding regions found at the ends of eukaryotic linear chromosomes. Although they have traditionally been associated with the protection of linear DNA ends to avoid gene losses during each round of DNA replication, recent studies have demonstrated that the role of these sequences and their adjacent regions go beyond just protecting chromosomal ends. Regions nearby to telomeric sequences have now been identified as having increased variability in the form of duplications and rearrangements that result in new functional abilities and biodiversity. Furthermore, unique fungal telomeric and chromatin structures have now extended clinical capabilities and understanding of pathogenicity …
Draft Genome Sequences Of 13 Vibrio Cholerae Strains From The Rio Grande Delta, Jeffrey W. Turner, Jorge Duran-Gonzalez, David A. Laughlin, Daniel Unterweger, David Silva, Boris Ermolinsky, Stefan Pukatzki, Daniele Provenzano
Draft Genome Sequences Of 13 Vibrio Cholerae Strains From The Rio Grande Delta, Jeffrey W. Turner, Jorge Duran-Gonzalez, David A. Laughlin, Daniel Unterweger, David Silva, Boris Ermolinsky, Stefan Pukatzki, Daniele Provenzano
Publications and Research
Vibrio cholerae is the etiologic agent of cholera, an acute and often fatal diarrheal disease that affects millions globally. We report the draft genome sequences of 13 non-O1/O139 V. cholerae strains isolated from the Rio Grande Delta in Texas. These genomes will aid future analyses of environmental serovars.
Investigating Distribution Of Legionella Pneumophila In Urban And Suburban Watersheds, Azlan Maqbool
Investigating Distribution Of Legionella Pneumophila In Urban And Suburban Watersheds, Azlan Maqbool
Student Theses
The presence of Legionella pneumophila was assessed using a cultivation-based approach in New York City waterways, a freshwater portion of the lower Hudson River Estuary near Kingston NY, and in urban and suburban street water. Legionella pneumophila was detected in 51% of brackish New York City Estuary samples, most with concentrations near minimum detection (=>1 organism/ mL). In contrast, it was detected in 22% of suburban freshwater Hudson River Estuary samples. Levels of the bacterium were found to be higher during wet weather compared to dry weather in the highly dense urban setting, but not in the less dense …
Dom Degradation By Light And Microbes Along The Yukon River‑Coastal Ocean Continuum, Brice K. Grunert, Maria Tzortziou, Patrick Neale, Alana Menendez, Peter Hernes
Dom Degradation By Light And Microbes Along The Yukon River‑Coastal Ocean Continuum, Brice K. Grunert, Maria Tzortziou, Patrick Neale, Alana Menendez, Peter Hernes
Publications and Research
The Arctic is experiencing rapid warming, resulting in fundamental shifts in hydrologic connectivity and carbon cycling. Dissolved organic matter (DOM) is a significant component of the Arctic and global carbon cycle, and significant perturbations to DOM cycling are expected with Arctic warming. The impact of photochemical and microbial degradation, and their interactive effects, on DOM composition and remineralization have been documented in Arctic soils and rivers. However, the role of microbes, sunlight and their interactions on Arctic DOM alteration and remineralization in the coastal ocean has not been considered, particularly during the spring freshet when DOM loads are high, photoexposure …
Uncovering Potential Biofilm Modulators, Liliana Margent
Uncovering Potential Biofilm Modulators, Liliana Margent
Theses and Dissertations
Biofilms have negative and positive impacts depending on the context they develop. In this work, I optimized a biofilm assay to evaluate the effect of three different types of compounds indole derivatives, 2,5 Diketopiperazines, and 12-hydroxystearic acid on the biofilm formation of E. coli.
Human Ace2‑Functionalized Gold “Virus‑Trap” Nanostructures For Accurate Capture Of Sars‑Cov‑2 And Single‑Virus Sers Detection, Yong Yang, Yusi Peng, Chenglong Lin, Li Long, Jingying Hu, Jun He, Hui Zeng, Zhengren Huang, Zhi-Yuan Li, Masaki Tanemura, Jianlin Shi, John R. Lombardi, Xiaoying Luo
Human Ace2‑Functionalized Gold “Virus‑Trap” Nanostructures For Accurate Capture Of Sars‑Cov‑2 And Single‑Virus Sers Detection, Yong Yang, Yusi Peng, Chenglong Lin, Li Long, Jingying Hu, Jun He, Hui Zeng, Zhengren Huang, Zhi-Yuan Li, Masaki Tanemura, Jianlin Shi, John R. Lombardi, Xiaoying Luo
Publications and Research
The current COVID-19 pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus. Here, we present a Human Angiotensin-converting-enzyme 2 (ACE2)-functionalized gold “virus traps” nanostructure as an extremely sensitive SERS biosensor, to selectively capture and rapidly detect S-protein expressed coronavirus, such as the current SARS-CoV-2 in the contaminated water, down to the single-virus level. Such a SERS sensor features extraordinary 106- fold virus enrichment originating from high-affinity of ACE2 with S protein as well as “virus-traps” composed of oblique gold nanoneedles, and 109- fold enhancement of Raman signals originating from multicomponent SERS effects. Furthermore, the identification standard of virus …
Pirnas As Modulators Of Disease Pathogenesis, Kayla J. Rayford, Ayorinde Cooley, Jelonia T. Rumph, Ashutosh Arun, Girish Rachakonda, Fernando Villalta, Maria F. Lima, Siddharth Pratap, Smita Misra, Pius N. Nde
Pirnas As Modulators Of Disease Pathogenesis, Kayla J. Rayford, Ayorinde Cooley, Jelonia T. Rumph, Ashutosh Arun, Girish Rachakonda, Fernando Villalta, Maria F. Lima, Siddharth Pratap, Smita Misra, Pius N. Nde
Publications and Research
Advances in understanding disease pathogenesis correlates to modifications in gene expression within different tissues and organ systems. In depth knowledge about the dysregulation of gene expression profiles is fundamental to fully uncover mechanisms in disease development and changes in host homeostasis. The body of knowledge surrounding mammalian regulatory elements, specifically regulators of chromatin structure, transcriptional and translational activation, has considerably surged within the past decade. A set of key regulators whose function still needs to be fully elucidated are small non-coding RNAs (sncRNAs). Due to their broad range of unfolding functions in the regulation of gene expression during transcription and …
When The Pandemic Opts For The Lockdown: Secretion System Evolution In The Cholera Bacterium, Francis J. Santoriello, Stefan Pukatzki
When The Pandemic Opts For The Lockdown: Secretion System Evolution In The Cholera Bacterium, Francis J. Santoriello, Stefan Pukatzki
Publications and Research
Vibrio cholerae, the causative agent of the diarrheal disease cholera, is a microbe capable of inhabiting two different ecosystems: chitinous surfaces in brackish, estuarine waters and the epithelial lining of the human gastrointestinal tract. V. cholerae defends against competitive microorganisms with a contact-dependent, contractile killing machine called the type VI secretion system (T6SS) in each of these niches. The T6SS resembles an inverted T4 bacteriophage tail and is used to deliver toxic effector proteins into neighboring cells. Pandemic strains of V. cholerae encode a unique set of T6SS effector proteins, which may play a role in pathogenesis or pandemic …
The C. Neoformans Cell Wall: A Scaffold For Virulence, Christine Chrissian
The C. Neoformans Cell Wall: A Scaffold For Virulence, Christine Chrissian
Dissertations, Theses, and Capstone Projects
Cryptococcus neoformans is a globally distributed opportunistic fungal pathogen and the causative agent of life threatening cryptococcal meningoencephalitis in immunocompromised individuals, resulting in ~180,000 deaths each year worldwide. A primary virulence-associated trait of this organism is the production of melanin. Melanins are a class of diverse pigments produced via the oxidation and polymerization of aromatic ring compounds that have a characteristically complex, heterogenous, and amorphous structure. They are synthesized by representatives of all biological kingdoms and share a multitude of remarkable properties such as the ability to absorb ultraviolet (UV) light and protect against ionizing radiation. Melanin production in fungi …
A Peek Inside The Machines Of Bacterial Nucleotide Excision Repair, Thanyalak Kraithong, Silas Hartley, David Jeruzalmi, Danaya Pakotiprapha
A Peek Inside The Machines Of Bacterial Nucleotide Excision Repair, Thanyalak Kraithong, Silas Hartley, David Jeruzalmi, Danaya Pakotiprapha
Publications and Research
Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). …
Single-Cell Fluidic Force Microscopy Reveals Stress- Dependent Molecular Interactions In Yeast Mating, Marion Mathelié-Guinlet, Felipe Viela, JéRôMe Dehullu, Sviatlana Filimonava, Jason M. Rauceo, Peter N. Lipke, Yves F. DufrêNe
Single-Cell Fluidic Force Microscopy Reveals Stress- Dependent Molecular Interactions In Yeast Mating, Marion Mathelié-Guinlet, Felipe Viela, JéRôMe Dehullu, Sviatlana Filimonava, Jason M. Rauceo, Peter N. Lipke, Yves F. DufrêNe
Publications and Research
Sexual agglutinins of the budding yeast Saccharomyces cerevisiae are proteins mediating cell aggregation during mating. Complementary agglutinins expressed by cells of opposite mating types “a” and “α” bind together to promote agglutination and facilitate fusion of haploid cells. By means of an innovative single-cell manipulation assay combining fluidic force microscopy with force spectroscopy, we unravel the strength of single specific bonds between a- and α-agglutinins (~100 pN) which require pheromone induction. Prolonged cell–cell contact strongly increases adhesion between mating cells, likely resulting from an increased expression of agglutinins. In addition, we highlight the critical role of disulfide bonds of the …
Why Do Antibiotics Exist?, Fabrizio Spagnolo, Monica Trujillo, John J. Dennehy
Why Do Antibiotics Exist?, Fabrizio Spagnolo, Monica Trujillo, John J. Dennehy
Publications and Research
In the struggle with antibiotic resistance, we are losing. There is now a serious threat of moving into a postantibiotic world. High levels of resistance, in terms of both frequency and strength, have evolved against all clinically approved antibiotics worldwide. The usable life span of new clinically approved antibiotics is typically less than a decade before resistance reaches frequencies so high as to require only guarded usage. However, microbes have produced antibiotics for millennia without resistance becoming an existential issue. If resistance is the inevitable consequence of antibiotic usage, as has been the human experience, why has it not become …
Rotavirus A Genome Segments Show Distinct Segregation And Codon Usage Patterns, Irene Hoxie, John J. Dennehy
Rotavirus A Genome Segments Show Distinct Segregation And Codon Usage Patterns, Irene Hoxie, John J. Dennehy
Publications and Research
Reassortment of the Rotavirus A (RVA) 11-segment dsRNA genome may generate new genome constellations that allow RVA to expand its host range or evade immune responses. Reassortment may also produce phylogenetic incongruities and weakly linked evolutionary histories across the 11 segments, obscuring reassortment-specific epistasis and changes in substitution rates. To determine the co-segregation patterns of RVA segments, we generated time-scaled phylogenetic trees for each of the 11 segments of 789 complete RVA genomes isolated from mammalian hosts and compared the segments’ geodesic distances. We found that segments 4 (VP4) and 9 (VP7) occupied significantly different tree spaces from each other …
Pandemic Vibrio Cholerae Shuts Down Site-Specific Recombination To Retain An Interbacterial Defence Mechanism, Francis J. Santoriello, Lina Michel, Daniel Unterweger, Stefan Pukatzki
Pandemic Vibrio Cholerae Shuts Down Site-Specific Recombination To Retain An Interbacterial Defence Mechanism, Francis J. Santoriello, Lina Michel, Daniel Unterweger, Stefan Pukatzki
Publications and Research
Vibrio cholerae is an aquatic microbe that can be divided into three subtypes: harmless environmental strains, localised pathogenic strains, and pandemic strains causing global cholera outbreaks. Each type has a contact-dependent type VI secretion system (T6SS) that kills neighbouring competitors by translocating unique toxic effector proteins. Pandemic isolates possess identical effectors, indicating that T6SS effectors may affect pandemicity. Here, we show that one of the T6SS gene clusters (Aux3) exists in two states: a mobile, prophage-like element in a small subset of environmental strains, and a truncated Aux3 unique to and conserved in pandemic isolates. Environmental Aux3 can be readily …
Cryo‑Electron Microscopy Structure Of The 70s Ribosome From Enterococcus Faecalis, Eileen L. Murphy, Kavindra V. Singh, Bryant Avila, Torsten Kleffmann, Steven T. Gregory, Barbara E. Murray, Kurt L. Krause, Reza Khayat, Gerwald Jogl
Cryo‑Electron Microscopy Structure Of The 70s Ribosome From Enterococcus Faecalis, Eileen L. Murphy, Kavindra V. Singh, Bryant Avila, Torsten Kleffmann, Steven T. Gregory, Barbara E. Murray, Kurt L. Krause, Reza Khayat, Gerwald Jogl
Publications and Research
Enterococcus faecalis is a gram-positive organism responsible for serious infections in humans, but as with many bacterial pathogens, resistance has rendered a number of commonly used antibiotics ineffective. Here, we report the cryo-EM structure of the E. faecalis 70S ribosome to a global resolution of 2.8 Å. Structural differences are clustered in peripheral and solvent exposed regions when compared with Escherichia coli, whereas functional centres, including antibiotic binding sites, are similar to other bacterial ribosomes. Comparison of intersubunit conformations among five classes obtained after three-dimensional classification identifies several rotated states. Large ribosomal subunit protein bL31, which forms intersubunit bridges to …