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Host Immunity Increases Mycobacterium Tuberculosis Reliance On Cytochrome Bd Oxidase [Preprint], Yi Cai, Eleni Jaecklein, Jared Mackenzie, Kadamba Papavinasasundaram, Michigan State University, Xinchun Chen, Africa Health Research Institute, Christopher M. Sassetti 2020 Shenzhen University

Host Immunity Increases Mycobacterium Tuberculosis Reliance On Cytochrome Bd Oxidase [Preprint], Yi Cai, Eleni Jaecklein, Jared Mackenzie, Kadamba Papavinasasundaram, Michigan State University, Xinchun Chen, Africa Health Research Institute, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

In order to sustain a persistent infection, Mycobacterium tuberculosis (Mtb) must adapt to a changing environment that is shaped by the developing immune response. This necessity to adapt is evident in the flexibility of many aspects of Mtb metabolism, including a respiratory chain that consists of two distinct terminal cytochrome oxidase complexes. Under the conditions tested thus far, the bc1/aa3 complex appears to play a dominant role, while the alternative bd oxidase is largely redundant. However, presence of two terminal oxidases in this obligate pathogen implies that respiratory requirements might change during infection. We report that the ...


Distinct Bacterial Pathways Influence The Efficacy Of Antibiotics Against Mycobacterium Tuberculosis, Michelle Bellerose, Megan K. Proulx, Clare M. Smith, Richard E. Baker, Thomas R. Ioerger, Christopher M. Sassetti 2020 University of Massachusetts Medical School

Distinct Bacterial Pathways Influence The Efficacy Of Antibiotics Against Mycobacterium Tuberculosis, Michelle Bellerose, Megan K. Proulx, Clare M. Smith, Richard E. Baker, Thomas R. Ioerger, Christopher M. Sassetti

Open Access Articles

Effective tuberculosis treatment requires at least 6 months of combination therapy. Alterations in the physiological state of the bacterium during infection are thought to reduce drug efficacy and prolong the necessary treatment period, but the nature of these adaptations remain incompletely defined. To identify specific bacterial functions that limit drug effects during infection, we employed a comprehensive genetic screening approach to identify mutants with altered susceptibility to the first-line antibiotics in the mouse model. We identified many mutations that increase the rate of bacterial clearance, suggesting new strategies for accelerating therapy. In addition, the drug-specific effects of these mutations suggested ...


Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System [Preprint], Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti 2020 Michigan State University

Mycobacterium Tuberculosis Evasion Of Guanylate Binding Protein-Mediated Host Defense In Mice Requires The Esx1 Secretion System [Preprint], Andrew J. Olive, Clare M. Smith, Christina E. Baer, Jörn Coers, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer of cell-autonomous immunity is the lymphocyte-derived cytokine IFNγ. While the production of IFNγ by T cells is essential to protect against Mtb, it is not capable of fully eradicating Mtb infection. This suggests that Mtb evades a subset of IFNγ-mediated antimicrobial responses, yet what mechanisms Mtb resists remains unclear. The IFNγ-inducible Guanylate binding proteins (GBPs) are key host defense proteins able to control infections with intracellular pathogens. GBPs were previously shown ...


Biofilm Structure Promotes Coexistence Of Phage-Resistant And Phage-Susceptible Bacteria, Emilia L. Simmons, Matthew C. Bond, Britt Koskella, Knut Drescher, Vanni Bucci, Carey D. Nadell 2020 Dartmouth College

Biofilm Structure Promotes Coexistence Of Phage-Resistant And Phage-Susceptible Bacteria, Emilia L. Simmons, Matthew C. Bond, Britt Koskella, Knut Drescher, Vanni Bucci, Carey D. Nadell

Open Access Articles

Encounters among bacteria and their viral predators (bacteriophages) are among the most common ecological interactions on Earth. These encounters are likely to occur with regularity inside surface-bound communities that microbes most often occupy in natural environments. Such communities, termed biofilms, are spatially constrained: interactions become limited to near neighbors, diffusion of solutes and particulates can be reduced, and there is pronounced heterogeneity in nutrient access and physiological state. It is appreciated from prior theoretical work that phage-bacteria interactions are fundamentally different in spatially structured contexts, as opposed to well-mixed liquid culture. Spatially structured communities are predicted to promote the protection ...


Fecal Microbiota Transplantation And Gut Microbiome Effects On Psychiatric Illnesses, Mona Seresht 2020 Dominican University of California

Fecal Microbiota Transplantation And Gut Microbiome Effects On Psychiatric Illnesses, Mona Seresht

Physician Assistant Studies | Student Articles

Despite the medical advances that have been made in regards to mental health, psychiatric medications, and alternative therapies, many patients continue to suffer day in and day out, unable to live the type of life they desire. Many times, the medication route includes many episodes of trial and error, side effects, and no significant improvement in actual symptoms. Therapy, although effective, typically necessitates a supplemental medication for the best results. Fecal microbiota transplantation (FMT) is a method where feces from a healthy donor is transferred to an affected patient, typically via colonoscopy. Theoretically, this alters the gut microbiome in a ...


Multicenter Clinical Evaluation Of The Revogene Strep A Molecular Assay For Detection Of Streptococcus Pyogenes From Throat Swab Specimens, Dithi Banerjee, Jeff Michael, B. Schmitt, H. Salimnia, N. Mhaissen, D. M. Goldfarb, P. Lachance, M. L. Faron, T. Aufderheide, N. Ledeboer, A. Weissfeld, Rangaraj Selvarangan 2020 Children's Mercy Hospital

Multicenter Clinical Evaluation Of The Revogene Strep A Molecular Assay For Detection Of Streptococcus Pyogenes From Throat Swab Specimens, Dithi Banerjee, Jeff Michael, B. Schmitt, H. Salimnia, N. Mhaissen, D. M. Goldfarb, P. Lachance, M. L. Faron, T. Aufderheide, N. Ledeboer, A. Weissfeld, Rangaraj Selvarangan

Manuscripts, Articles, Book Chapters and Other Papers

Copyright © 2020 Banerjee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license Group A streptococcus (GAS) species cause bacterial pharyngitis in both adults and children. Early and accurate diagnosis of GAS is important for appropriate antibiotic therapy to prevent GAS sequalae. The Revogene Strep A molecular assay (Meridian Bioscience Canada Inc, Quebec City, QC, Canada) is an automated real-time PCR assay for GAS detection from throat swab specimens within approximately 70 min. This multicenter prospective study evaluated the performance of the Revogene Strep A molecular assay compared to that ...


Identifying Determinants Of Target Specificity In Two Related Bacterial Peptide Toxins, Andrew D. Holmes 2020 University of South Dakota

Identifying Determinants Of Target Specificity In Two Related Bacterial Peptide Toxins, Andrew D. Holmes

Honors Thesis

Toxin-antitoxin (TA) systems were originally identified as two-component systems ensuring the stable inheritance of plasmids in bacterial populations. Recently, they have been identified on bacterial chromosomes where their functions remain mostly undefined. The par locus of E. faecalis plasmid pAD1 (parpAD1) was the first TA system defined in a Gram-positive bacterium and a homolog encoded on the E. faecalis chromosome (parEF0409) was later described. Related loci numbering in the hundreds have been identified throughout Gram-positive bacteria based on homology to the toxin of the system, Fst, and similarities in genetic organization and regulation. Despite their similar sequences, over-expression ...


Linearized Siderophore Products Secreted Via Macab Efflux Pump Protect Salmonella Enterica Serovar Typhimurium From Oxidative Stress, L M. Bogomolnaya, Ronak Tilvawala, J. R. Elfenbein, J. D. Cirillo, H. L. Andrews-Polymenis 2020 Texas A&M University

Linearized Siderophore Products Secreted Via Macab Efflux Pump Protect Salmonella Enterica Serovar Typhimurium From Oxidative Stress, L M. Bogomolnaya, Ronak Tilvawala, J. R. Elfenbein, J. D. Cirillo, H. L. Andrews-Polymenis

Open Access Articles

Nontyphoidal salmonellae (NTS) are exposed to reactive oxygen species (ROS) during their residency in the gut. To survive oxidative stress encountered during infection, salmonellae employ several mechanisms. One of these mechanisms involves the multidrug efflux pump MacAB, although the natural substrate of this pump has not been identified. MacAB homologs in pseudomonads secrete products of nonribosomal peptide synthesis (NRPS). In Salmonella enterica serovar Typhimurium, the siderophore enterobactin is produced by NRPS in response to iron starvation and this molecule can be processed into salmochelin and several linear metabolites. We found that Salmonella mutants lacking the key NRPS enzyme EntF are ...


Bacterial Load In Virtual Reality Headsets, Benjamin Creel 2020 University of Mississippi

Bacterial Load In Virtual Reality Headsets, Benjamin Creel

Honors Theses

Virtual reality technology is a rapidly growing field of computer science. Virtual reality utilizes headsets which cover the user’s eyes, nose, and forehead. In this study, I analyzed the potential for these headsets to become contaminated with bacteria. The nosepieces and foreheads of two HTC Vive VR headsets of the Department of Computer Science of the University of Mississippi were sampled over the course of a seven-week Immersive Media (CSCI 447) course. Serial dilutions were performed, and samples were plated on various culture media. Following incubation, counts of bacteria were determined. DNA was extracted from bacterial growth on plates ...


Epidemiologic Survey Of Legionella Urine Antigen Testing Within A Large Wisconsin-Based Health Care System, Caroline P. Toberna, Hannah M. William, Jessica J. F. Kram, Kayla Heslin, Dennis J. Baumgardner 2020 Aurora Research Institute; Center for Urban Population Health; Aurora UW Medical Group, Aurora Health Care

Epidemiologic Survey Of Legionella Urine Antigen Testing Within A Large Wisconsin-Based Health Care System, Caroline P. Toberna, Hannah M. William, Jessica J. F. Kram, Kayla Heslin, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Purpose: Legionella pneumophila pneumonia is a life-threatening, environmentally acquired infection identifiable via Legionella urine antigen tests (LUAT). We aimed to identify cumulative incidence, demographic distribution, and undetected disease outbreaks of Legionella pneumonia via positive LUAT in a single eastern Wisconsin health system, with a focus on urban Milwaukee County.

Methods: A multilevel descriptive ecologic study was conducted utilizing electronic medical record data from a large integrated health care system of patients who underwent LUAT from 2013 to 2017. A random sample inclusive of all positive tests was reviewed to investigate geodemographic differences among patients testing positive versus negative. Statistical comparisons ...


Characterization Of Nasal Isolates Of Staphylococcus Aureus From Concordia's Campus, Jeenue Vang 2020 Concordia University St. Paul

Characterization Of Nasal Isolates Of Staphylococcus Aureus From Concordia's Campus, Jeenue Vang

Research and Scholarship Symposium Posters

Research students from the Concordia University, St. Paul Science Department has collected over 1,000 nasal swabs over the past 5 years in an attempt to characterize nasal isolates of Staphylococcus aureus from healthy individuals. S. aureus is a common commensal bacterium found on the skin, in the nares, or in the vaginal tract of approximately 30% of the population. While S. aureus is typically harmless when it is growing in those areas, it can also pose a public health risk as it can act as an opportunistic pathogen to cause a variety of infections, such as toxic shock syndrome ...


Staphylococcus Aureus May Be Living In Your Nasal Cavity Right Now, Hannah Pedersen 2020 Concordia University St. Paul

Staphylococcus Aureus May Be Living In Your Nasal Cavity Right Now, Hannah Pedersen

Research and Scholarship Symposium Posters

Staphylococcus aureus is a dual role bacterium and is able to live commensally in some patients, but can cause disease in others. Methicillin resistant S. aureus (MRSA) causes life threatening disease in patients and can be very hard to treat since it is resistant to many antibiotics. In order for S. aureus to wreak havoc on the body, it must be able to have specific genes expressed to secrete toxins. These toxins are what causes the patients to get a wide variety of symptoms like boils, scalded skin, toxic shock syndrome, pneumonia or sepsis. This study tested eleven different isolates ...


Biological Sex Influences Susceptibility To Acinetobacter Baumannii Pneumonia In Mice, Sílvia Pires, Adeline Peignier, Jeremy Seto, Davida S. Smyth, Dane Parker 2020 Rutgers University - Newark

Biological Sex Influences Susceptibility To Acinetobacter Baumannii Pneumonia In Mice, Sílvia Pires, Adeline Peignier, Jeremy Seto, Davida S. Smyth, Dane Parker

Publications and Research

Acinetobacter baumannii (A. baumannii) is an extremely versatile multidrug-resistant pathogen with a very high mortality rate; therefore, it has become crucial to understand the host response during its infection. Given the importance of mice for modeling infection and their role in preclinical drug development, equal emphasis should be placed on the use of both sexes. Through our studies using a murine model of acute pneumonia with A. baumannii, we observed that female mice were more susceptible to infection. Likewise, treatment of male mice with estradiol increased their susceptibility to infection. Analysis of the airway compartment revealed enhanced inflammation and reduced ...


Impacts On Fitness Associated With Acquisition Of Gut Microbiota In Drosophila, Corinne Topolski 2020 Grand Valley State University

Impacts On Fitness Associated With Acquisition Of Gut Microbiota In Drosophila, Corinne Topolski

Honors Projects

Drosophila melanogaster is a model organism that has been studied to demonstrate the role of gut microbiota in fitness. It has already been established the gut microbiota is extremely important for the health of the organism, but the source of the microbiota has not been studied as thoroughly. In order to test if the source of microbiota affects the fitness of the individual, adult male and female flies were placed onto plates to defecate after being raised on standard food and food with carbenicillin. Stock eggs were washed in either water or a bleach solution, then placed on the defecation ...


Detection And Quantification Of Bacterial Species Important To Mental And Physical Health, David G. Leonard 2020 Air Force Institute of Technology

Detection And Quantification Of Bacterial Species Important To Mental And Physical Health, David G. Leonard

Theses and Dissertations

The human gut microbiome contains an abundance of microorganisms which could influence mental health as well as physical health. These microorganisms produce chemicals which affect the brain and the body in various ways. Probiotic bacteria and yeasts have been studied to determine effects they have on mice, rats, and humans to illustrate the importance these microorganisms on health. Studies have shown that adding beneficial microorganisms to the human diet can have positive effects on mental and physical health, to include lessening symptoms of depression and anxiety, lessen gastrointestinal inflammation, displacing pathogens, and improving immunomodulatory response. A quantitative way to identify ...


Cell Cycle-Associated Expression Patterns Predict Gene Function In Mycobacteria [Preprint], Aditya Bandekar, Sishir Subedi, Thomas Ioerger, Christopher M. Sassetti 2020 University of Massachusetts Medical School

Cell Cycle-Associated Expression Patterns Predict Gene Function In Mycobacteria [Preprint], Aditya Bandekar, Sishir Subedi, Thomas Ioerger, Christopher M. Sassetti

University of Massachusetts Medical School Faculty Publications

While the major events in prokaryotic cell cycle progression are likely to be coordinated with transcriptional and metabolic changes, these processes remain poorly characterized. Unlike many rapidly-growing bacteria, DNA replication and cell division are temporally-resolved in mycobacteria, making these slow-growing organisms a potentially useful system to investigate the prokaryotic cell cycle. To determine if cell-cycle dependent gene regulation occurs in mycobacteria, we characterized the temporal changes in the transcriptome of synchronously replicating populations of Mycobacterium tuberculosis (Mtb). By enriching for genes that display a sinusoidal expression pattern, we discover 485 genes that oscillate with a period consistent with the cell ...


Chrysin‐Loaded Chitosan Nanoparticles Potentiates Antibiofilm Activity Against Staphylococcus Aureus, Busi Siddhardha, Uday Pandey, K. Kaviyarasu, Rajasekharreddy Pala, Asad Syed, Ali K. Bahkali, Abdallah M. Elgorban 2020 Pondicherry University

Chrysin‐Loaded Chitosan Nanoparticles Potentiates Antibiofilm Activity Against Staphylococcus Aureus, Busi Siddhardha, Uday Pandey, K. Kaviyarasu, Rajasekharreddy Pala, Asad Syed, Ali K. Bahkali, Abdallah M. Elgorban

Pharmacy Faculty Articles and Research

The application of nanotechnology in medicine is gaining popularity due to its ability to increase the bioavailability and biosorption of numerous drugs. Chrysin, a flavone constituent of Orocylumineicum vent is well‐reported for its biological properties. However, its therapeutic potential has not been fully exploited due to its poor solubility and bioavailability. In the present study, chrysin was encapsulated into chitosan nanoparticles using TPP as a linker. The nanoparticles were characterized and investigated for their anti‐biofilm activity against Staphylococcus aureus. At sub‐Minimum Inhibitory Concentration, the nanoparticles exhibited enhanced anti‐biofilm efficacy against S. aureus as compared to its ...


Long Non-Coding Rna Lincrna-Eps Inhibits Host Defense Against Listeria Monocytogenes Infection, Federica Agliano, Katherine A. Fitzgerald, Anthony T. Vella, Vijay A. Rathinam, Andrei E. Medvedev 2020 University of Connecticut

Long Non-Coding Rna Lincrna-Eps Inhibits Host Defense Against Listeria Monocytogenes Infection, Federica Agliano, Katherine A. Fitzgerald, Anthony T. Vella, Vijay A. Rathinam, Andrei E. Medvedev

Open Access Articles

Long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several biological systems. The long intergenic RNA-erythroid pro-survival (lincRNA-EPS) has been shown to play a critical role in restraining inflammatory gene expression. However, the function of lincRNA-EPS during bacterial infections remains unknown. Here, we demonstrate that following infection with the intracellular bacterium Listeria monocytogenes, both mouse macrophages and dendritic cells lacking lincRNA-EPS exhibit an enhanced expression of proinflammatory cytokine genes, as well as an increased expression of the inducible nitric oxide synthase (iNos) and nitric oxide (NO) production. Importantly, we found that lincRNA-EPS(-/-) mice intraperitoneally infected with ...


Combining Citizen Science And Genomics To Investigate Tick, Pathogen, And Commensal Microbiome At Single-Tick Resolution, Gaurav Chauhan, Jesse McClure, Jessica Hekman, Patrick W. Marsh, Jeffrey A. Bailey, Rachel F. Daniels, Diane P. Genereux, Elinor K. Karlsson 2020 University of Massachusetts Medical School

Combining Citizen Science And Genomics To Investigate Tick, Pathogen, And Commensal Microbiome At Single-Tick Resolution, Gaurav Chauhan, Jesse Mcclure, Jessica Hekman, Patrick W. Marsh, Jeffrey A. Bailey, Rachel F. Daniels, Diane P. Genereux, Elinor K. Karlsson

Open Access Articles

The prevalence of tickborne diseases worldwide is increasing virtually unchecked due to the lack of effective control strategies. The transmission dynamics of tickborne pathogens are influenced by the tick microbiome, tick co-infection with other pathogens, and environmental features. Understanding this complex system could lead to new strategies for pathogen control, but will require large-scale, high-resolution data. Here, we introduce Project Acari, a citizen science-based project to assay, at single-tick resolution, species, pathogen infection status, microbiome profile, and environmental conditions of tens of thousands of ticks collected from numerous sites across the United States. In the first phase of the project ...


Extensively Drug-Resistant Pseudomonas Aeruginosa In Vitro Susceptibility And Mechanisms Of Resistance, Chanah Gallagher 2020 University of Kentucky

Extensively Drug-Resistant Pseudomonas Aeruginosa In Vitro Susceptibility And Mechanisms Of Resistance, Chanah Gallagher

Theses and Dissertations--Pharmacy

Pseudomonas aeruginosa causes severe healthcare-associated infections. Forty-eight extensively drug-resistant (XDR)-P. aeruginosa isolates were selected from 287 isolates collected for evaluation based on clinical susceptibility data. In vitro activity of commonly utilized antimicrobials (i.e. antipseudomonal beta-lactams, aminoglycosides, fluoroquinolones, and polymyxins) plus ceftolozane-tazobactam, ceftazidime-avibactam, and aztreonam-avibactam against XDR-P. aeruginosa were determined. The mechanism of resistance profile was determined through phenotypic expression analysis. Overall, polymyxin B and colistin were 100% susceptible. Apart from the polymyxins, ceftolozane-tazobactam had the highest susceptibility (94%) followed by ceftazidime-avibactam (90%) and amikacin (83%). Ceftolozane-tazobactam activity was not significantly different from ceftazidime-avibactam (p=0.6831). Only ...


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