Microbiology Commons^™

Crystal Structure Of Sars-Cov-2 Main Protease In Complex With The Non-Covalent Inhibitor Ml188, Gordon J. Lockbaum, Archie C. Reyes, Jeong Min Lee, Ronak Tilvawala, Ellen A. Nalivaika, Akbar Ali, Nese Kurt Yilmaz, Paul R. Thompson, Celia A. Schiffer

COVID-19 Publications by UMMS Authors

Viral proteases are critical enzymes for the maturation of many human pathogenic viruses and thus are key targets for direct acting antivirals (DAAs). The current viral pandemic caused by SARS-CoV-2 is in dire need of DAAs. The Main protease (M(pro)) is the focus of extensive structure-based drug design efforts which are mostly covalent inhibitors targeting the catalytic cysteine. ML188 is a non-covalent inhibitor designed to target SARS-CoV-1 M(pro), and provides an initial scaffold for the creation of effective pan-coronavirus inhibitors. In the current study, we found that ML188 inhibits SARS-CoV-2 M(pro) at 2.5 microM, which is ...

Exploring The Impact Of Ketodeoxynonulosonic Acid In Host-Pathogen Interactions Using Uptake And Surface Display By Nontypeable Haemophilus Influenzae, Sudeshna Saha, Sanjay Ram, Ajit Varki

Open Access Publications by UMMS Authors

Surface expression of the common vertebrate sialic acid (Sia) N-acetylneuraminic acid (Neu5Ac) by commensal and pathogenic microbes appears structurally to represent "molecular mimicry" of host sialoglycans, facilitating multiple mechanisms of host immune evasion. In contrast, ketodeoxynonulosonic acid (Kdn) is a more ancestral Sia also present in prokaryotic glycoconjugates that are structurally quite distinct from vertebrate sialoglycans. We detected human antibodies against Kdn-terminated glycans, and sialoglycan microarray studies found these anti-Kdn antibodies to be directed against Kdn-sialoglycans structurally similar to those on human cell surface Neu5Ac-sialoglycans. Anti-Kdn-glycan antibodies appear during infancy in a pattern similar to those generated following incorporation of ...

Metabolomics-Based Analysis Of Miniature Flask Contents Identifies Tobacco Mixture Use Among The Ancient Maya, Mario Zimmermann, Korey J. Brownstein, Luis Pantoja Díaz, Iliana Ancona Aragón, Scott R. Hutson, Barry Kidder, Shannon Tushingham, David R. Gang

Anthropology Faculty Publications

A particular type of miniature ceramic vessel locally known as “veneneras” is occasionally found during archaeological excavations in the Maya Area. To date, only one study of a collection of such containers successfully identified organic residues through coupled chromatography–mass spectrometry methods. That study identified traces of nicotine likely associated with tobacco. Here we present a more complete picture by analyzing a suite of possible complementary ingredients in tobacco mixtures across a collection of 14 miniature vessels. The collection includes four different vessel forms and allows for the comparison of specimens which had previously formed part of museum exhibitions with ...

Innate Lymphoid Cells And Disease Tolerance In Sars-Cov-2 Infection [Preprint], Noah J. Silverstein, Yetao Wang, Zachary Manickas-Hill, Claudia C. Carbone, Ann Dauphin, Mgh Covid-19 Collection & Processing Team, Jonathan Z. Li, Bruce D. Walker, Xu G. Yu, Jeremy Luban

University of Massachusetts Medical School Faculty Publications

BACKGROUND: Risk of severe coronavirus disease 2019 (COVID-19) increases with age, is greater in males, and is associated with decreased numbers of blood lymphoid cells. Though the reasons for these robust associations are unclear, effects of age and sex on innate and adaptive lymphoid subsets, including on homeostatic innate lymphoid cells (ILCs) implicated in disease tolerance, may underlie the effects of age and sex on COVID-19 morbidity and mortality.

METHODS: Flow cytometry was used to quantitate subsets of blood lymphoid cells from people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comparing those hospitalized with severe COVID-19 (n=40 ...

Disrupted Iron Metabolism And Mortality During Co-Infection With Malaria And An Intestinal Gram-Negative Extracellular Pathogen, Luara Isabela Dos Santos, Thais Abdala Torres, Suelen Queiroz. Diniz, Ricardo Goncalves, Gustavo Caballero-Flores, Gabriel Nunez, Ricardo T. Gazzinelli, Kevin Joseph. Maloy, Lis Ribeiro Do V Antonelli

Open Access Publications by UMMS Authors

Individuals with malaria exhibit increased morbidity and mortality when infected with Gram-negative (Gr-) bacteria. To explore this experimentally, we performed co-infection of mice with Plasmodium chabaudi and Citrobacter rodentium, an extracellular Gr- bacterial pathogen that infects the large intestine. While single infections are controlled effectively, co-infection results in enhanced virulence that is characterized by prolonged systemic bacterial persistence and high mortality. Mortality in co-infected mice is associated with disrupted iron metabolism, elevated levels of plasma heme, and increased mitochondrial reactive oxygen species (ROS) production by phagocytes. In addition, iron acquisition by the bacterium plays a key role in pathogenesis because ...

Assessment Of Chlorine Resistance Enterobacter Cloacae Isolated From Water Storage Tanks In Sulaimaniyah City-Iraq, Hastyar H. Najmuldeen

Passer Journal

This study was designed to determine the extent of contamination of water storage tanks by non-lactose fermenter Enterobacter spp, and to characterize the chlorine and antibiotic resistance status. Moreover, to find the correlation between biofilm formation and resistance to chlorine. For this purpose, a total of 60 water samples were collected from residential and restaurant water storage tanks. Bacterial analysis and antibiotic susceptibility profiles of the samples were assessed by the Most Probable Number (MPN) and Vitek 2 compact tests, respectively. The biofilm formation was quantified by crystal violet staining method and chlorine resistance test by microdilution technique.

Obtained results ...

Two-Way Regulation Of Mmpl3 Expression Identifies And Validates Inhibitors Of Mmpl3 Function In Mycobacterium Tuberculosis, Shipra Grover, Curtis A. Engelhart, Esther Perez-Herran, Wei Li, Katherine A. Abrahams, Kadamba Papavinasasundaram, James M. Bean, Christopher M. Sassetti, Alfonso Mendoza-Losana, Gurdyal S. Besra, Mary Jackson, Dirk Schnappinger

Open Access Publications by UMMS Authors

MmpL3, an essential mycolate transporter in the inner membrane of Mycobacterium tuberculosis (Mtb), has been identified as a target of multiple, chemically diverse antitubercular drugs. However, several of these molecules seem to have secondary targets and inhibit bacterial growth by more than one mechanism. Here, we describe a cell-based assay that utilizes two-way regulation of MmpL3 expression to readily identify MmpL3-specific inhibitors. We successfully used this assay to identify a novel guanidine-based MmpL3 inhibitor from a library of 220 compounds that inhibit growth of Mtb by largely unknown mechanisms. We furthermore identified inhibitors of cytochrome bc1-aa3 oxidase as one class ...

Complete Genome Sequence Of Strain Ss-5, A Magnetotactic Gammaproteobacterium Isolated From The Salton Sea, A Shallow, Saline, Endorheic Rift Lake Located On The San Andreas Fault In California, Denis Trubitsyn, Caroline L. Monteil, Corey Geurink, Viviana Morillo Lopez, Luiz Gonzaga Paula De Almeida, Ana Tereza Ribeiro De Vasconcelos, Fernanda Abreu, Dennis A. Bazylinski, Christopher T. Lefevre

Life Sciences Faculty Publications

© 2021 American Society for Microbiology. All rights reserved. We report the 3.7-Mb genome sequence of strain SS-5, a magnetotactic, sulfur-oxidizing rod and member of the family Chromatiaceae of the class Gammaproteobacteria, which biomineralizes membrane-bound, elongated, prismatic octahedral, magnetite nanocrystals. This genome sequence brings further diversity for understanding the origin and evolution of magnetotaxis and magnetosome biomineralization.

The Intestinal And Oral Microbiomes Are Robust Predictors Of Covid-19 Severity The Main Predictor Of Covid-19-Related Fatality [Preprint], Doyle V. Ward, Shakti Bhattarai, Mayra Rojas-Correa, Ayan Purkayastha, Devon Holler, Ming Da Qu, William G. Mitchell, Jason D. Yang, Samuel Fountain, Abigail Zeamer, Catherine Forconi, Gavin Fujimori, Boaz Odwar, Caitlin Cawley, Beth A. Mccormick, Ann M. Moormann, Mireya Wessolossky, Vanni Bucci, Ana Maldonado-Contreras

University of Massachusetts Medical School Faculty Publications

The reason for the striking differences in clinical outcomes of SARS-CoV-2 infected patients is still poorly understood. While most recover, a subset of people become critically ill and succumb to the disease. Thus, identification of biomarkers that can predict the clinical outcomes of COVID-19 disease is key to help prioritize patients needing urgent treatment. Given that an unbalanced gut microbiome is a reflection of poor health, we aim to identify indicator species that could predict COVID-19 disease clinical outcomes. Here, for the first time and with the largest COVID-19 patient cohort reported for microbiome studies, we demonstrated that the intestinal ...

The Association Of Chest Radiographic Findings And Severity Scoring With Clinical Outcomes In Patients With Covid-19 Presenting To The Emergency Department Of A Tertiary Care Hospital In Pakistan, Raima Kaleemi, Kiran Hilal, Ainan Arshad, Russell Seth Martins, Avinash Nankani, Tanveer Ul Haq, Sundas Basharat, Zeeshan Ansar

Department of Radiology

Introduction: While chest x-rays (CXRs) represent a cost-effective imaging modality for developing countries like Pakistan, their utility for the prognostication of COVID-19 has been minimally explored. Thus, we describe the frequency and distribution of CXR findings, and their association with clinical outcomes of patients with COVID-19.
Methods: All adult (≥ 18 years) patients presenting between 28th February-31st May to the emergency department of a tertiary care hospital in Pakistan, who were COVID-19 positive on RT-PCR with CXR done on presentation, were included. A CXR Severity Score (CXR-SS) of 0-8 was used to quantify the extent of pulmonary infection on CXR, with ...

Disruption Of Cellular P-Bodies During An Adenovirus Infection​, La`Quita Randolph, Kevin Neubrecht, Kasey A. Karen

Graduate Research Posters

Adenovirus has made major contributions in medicine by serving as a model DNA virus to study other viruses, such as human papillomavirus (HPV). Adenoviruses are a diverse family of nonenveloped, double-stranded DNA viruses that are ubiquitous to animals and humans. There are over 67 serotypes of human adenoviruses that can cause a variety of illnesses including, gastroenteritis, conjunctivitis and respiratory infections. Adenovirus can cause these infections by invading host cells and producing an environment that is favorable for viral replication. During the early phases of infection, adenovirus expresses various viral proteins such as E4 11k, which has multiple functions. One ...

The Effect Of An Acidified-Gypsum Mixture On Broiler Litter Urease-Producing Bacteria And Nitrogen Mineralization, Taylor Chapman, Christopher D. Burt, Dave Bachoon, Miguel L. Cabrera, Christopher Horacek

Graduate Research Posters

Broiler chicken (Gallus gallus domesticus) production is one of the largest agricultural sectors in the state of Georgia. Broiler litter produced by broiler facilities is rich in organic nitrogen (N), specifically urea, which can be mineralized by poultry litter urease-producing bacteria (PLUP) forming ammoniacal-N (NH₃/NH₄⁺). A large portion of NH₃/NH₄⁺ can be lost as ammonia (NH₃) gas, which negatively impacts bird health and profitability. The release of NH₃ from litter is strongly influenced by the pH of the litter. Flue-gas desulfurization gypsum (FGDG) has been suggested as a potential amendment to reduce ...

Monitoring Lake Sinclair, Margaret Blackledge

Graduate Research Posters

Algae, a polyphyletic group of aquatic primary producers, play a great part in earth’s biosphere. They produce half of the world’s oxygen and are major contributors to aquatic biodiversity. When conditions are favorable to a species, algae will bloom. Some algal species will produce algal toxins during a bloom as a potential mechanism to concentrate carbon. Due to the integral part they play in aquatic food webs, nutrient cycling and the potential for harmful algal blooms, algal communities are monitored to determine the health and safety of aquatic environments. Lake Sinclair in middle Georgia is a good model ...

The 20th Anniversary Meeting Of The Rocky Mountain Virology Association, Joel Rovnak, Laura A. St Clair, Carley Mcalister, Chinemerem P. Ogbu, Jessica Smolenske, Randall J. Cohrs, Rushika Perera

Virology Papers

Due to the COVID-19 pandemic and multiple devastating forest fires, the 2020 meeting of the Rocky Mountain Virology Association was held virtually. The three-day gathering featured talks describing recent advances in virology and prion research. The keynote presentation described the measles virus paradox of immune suppression and life-long immunity. Special invited speakers presented information concerning visualizing antiviral effector cell biology in mucosal tissues, uncovering the T-cell tropism of Epstein-Barr virus type 2, a history and current survey of coronavirus spike proteins, a summary of Zika virus vaccination and immunity, the innate immune response to flavivirus infections, a discussion concerning prion ...

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars-Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum J. Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Virology Papers

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by ...

Strategies Targeting Hemagglutinin As A Universal Influenza Vaccine, Brianna L. Bullard, Eric A. Weaver

Virology Papers

Influenza virus has significant viral diversity, both through antigenic drift and shift, which makes development of a vaccine challenging. Current influenza vaccines are updated yearly to in- clude strains predicted to circulate in the upcoming influenza season, however this can lead to a mismatch which reduces vaccine efficacy. Several strategies targeting the most abundant and im- munogenic surface protein of influenza, the hemagglutinin (HA) protein, have been explored. These strategies include stalk-directed, consensus-based, and computationally derived HA immunogens. In this review, we explore vaccine strategies which utilize novel antigen design of the HA protein to improve cross-reactive immunity for development ...

Zika Virus Infection Induces Endoplasmic Reticulum Stress And Apoptosis In Placental Trophoblasts, Philma Glora Muthuraj, Prakask K. Sahoo, Madison Kraus, Taylor Bruett, Arun S. Annamalai, Aryamav Pattnaik, Asit K. Pattnaik, Siddappa N. Byrareddy, Sathish Kumar Natarajan

Virology Papers

Zika virus (ZIKV) infection to a pregnant woman can be vertically transmitted to the fetus via the placenta leading to Congenital Zika syndrome. This is characterized by microcephaly, retinal defects, and intrauterine growth retardation. ZIKV induces placental trophoblast apoptosis leading to severe abnormalities in the growth and development of the fetus. However, the molecular mechanism behind ZIKV-induced apoptosis in placental trophoblasts remains unclear. We hypothesize that ZIKV infection induces endoplasmic reticulum (ER) stress in the trophoblasts, and sustained ER stress results in apoptosis. HTR-8 (HTR-8/SVneo), a human normal immortalized trophoblast cell and human choriocarcinoma-derived cell lines (JEG-3 and JAR ...

Chlorovirus Pbcv-1 Multidomain Protein A111/114r Has Three Glycosyltransferase Functions Involved In The Synthesis Of Atypical N-Glycans, Eric Noel, Anna Notaro, Immacolata Speciale, Garry A. Duncan, Cristina De Castro, James L. Van Etten

Virology Papers

The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life. All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars. A combination of ge- netic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each. Here, in addition to in silico ...

Microaerophilic Oxidation Of Fe(Ii) Coupled With Simultaneous Carbon Fixation And As(Iii) Oxidation And Sequestration In Karstic Paddy Soil, Hui Tong, Chunju Zheng, Bing Li, Elizabeth D. Swanner, Chengshuai Liu, Manjia Chen, Yafei Xia, Yuhui Liu, Zengping Ning, Fangbai Li, Xinbin Feng

Geological and Atmospheric Sciences Publications

Microaerophilic Fe(II)-oxidizing bacteria are often chemolithoautotrophs, and the Fe(III) (oxyhydr)oxides they form could immobilize arsenic (As). If such microbes are active in karstic paddy soils, their activity would help increase soil organic carbon and mitigate As contamination. We therefore used gel-stabilized gradient systems to cultivate microaerophilic Fe(II)-oxidizing bacteria from karstic paddy soil to investigate their capacity for Fe(II) oxidation, carbon fixation, and As sequestration. Stable isotope probing (SIP) demonstrated the assimilation of inorganic carbon at a maximum rate of 8.02 mmol C m-2 d-1. Sequencing revealed that Bradyrhizobium, Cupriavidus, Hyphomicrobium, Kaistobacter, Mesorhizobium ...

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars- Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Virology Papers

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by ...