Pathogenic Microbiology Commons^™

Listeria Adhesion Protein Orchestrates Caveolae-Mediated Apical Junctional Remodeling Of Epithelial Barrier For Listeria Monocytogenes Translocation, Rishi Drolia, Donald B. Bryant, Shivendra Tenguria, Zuri A. Jules-Culver, Jessie Thind, Breanna Amelunke, Donqi Liu, Nicholas L. F. Gallina, Krishna K. Mishra, Manalee Samaddar, Manoj R. Sawale, Dharmendra K. Mishra, Abigail D. Cox, Arun K. Bhunia

Biological Sciences Faculty Publications

The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap− or ΔinlA) or double (lap−ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates …

Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu²⁺ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Evaluating Edna Metabarcoding As A Mic-Roe-Scopic Net To Catch Salmon Pathogens, Noah Burby

Honors College

Wild Atlantic salmon in the Gulf of Maine (GOM) is a Distinct Population Segment (DPS) that has been listed since 2000 as endangered by the U.S. Fish and Wildlife Service (USFWS) and the National Oceanic and Atmospheric Administration (NOAA). The current challenge is year-over-year decreases in the number of mature salmon returning to the Penobscot River for reproduction. Early detection of pathogen presence could allow for the identification of infection and the application of corrective measures. Environmental DNA (eDNA) is simply DNA that is collected from environmental samples (e.g., water, air, and soils), which consists of whole microorganisms and genetic …

Syndemics And Social Factors: Infectious Disease Patterns Within The Population Of People Experiencing Homelessness In The United States, Kathleen Berzonsky

Honors Theses

Individuals experiencing homelessness are at increased risk of suffering from infectious diseases. This is due to a number of social factors and healthcare disparities, as well as the idea of syndemics, by which diseases cluster together to worsen disease burden. Current intervention strategies approach treatment from a post-infection perspective, but reducing transmission rates of infectious diseases within the population of people experiencing homelessness will require a shift in the healthcare framework. The issue of people experiencing homelessness must be viewed through a biosocial lens, focusing on preventative care and treatment. I provide an overview of the social factors governing infectious …

Marineepi: A Gui-Based Matlab Toolbox To Simulate Marine Pathogen Transmission, Gorka Bidegain, Tal Ben-Horin, Eric N. Powell, John M. Klinck, Eileen E. Hofmann

CCPO Publications

The Graphical User Interface (GUI) MarineEpi is presented as a Matlab toolbox for easily (i) constructing disease transmission models for different marine host-pathogen systems, (ii) running simulations by specifying initial conditions and model parameters, and (iii) interpreting the resulting time series of the host and pathogen population dynamics. MarineEpi users can generate models for systems in which pathogen transmission occurs through contact with infected individuals (SI), contact with dead infected individuals (SID), contact with environmental pathogens released by infected individuals (SIP), and contact with environmental pathogens released by dead infected individuals (SIPD). MarineEpi is a freely available GUI that provides …

Multipatch Stochastic Epidemic Model For The Dynamics Of A Tick-Borne Disease, Milliward Maliyoni, Holly D. Gaff, Keshlan S. Govinder, Faraimunashe Chirove

Biological Sciences Faculty Publications

Spatial heterogeneity and migration of hosts and ticks have an impact on the spread, extinction and persistence of tick-borne diseases. In this paper, we investigate the impact of between-patch migration of white-tailed deer and lone star ticks on the dynamics of a tick-borne disease with regard to disease extinction and persistence using a system of Itô stochastic differential equations model. It is shown that the disease-free equilibrium exists and is unique. The general formula for computing the basic reproduction number for all patches is derived. We show that for patches in isolation, the basic reproduction number is equal to the …

Characterizing The Cutaneous Microbiome Of Eurycea Lucifuga As A Potential Defense Against Chytridiomycosis, Madeline Key

Senior Honors Theses

Chytridiomycosis is an emerging infectious disease that is significantly reducing global amphibian populations. The disease is caused by Batrachochytrium dendrobatidis (Bd), a fungus that lethally modifies amphibian skin. Recent research has suggested that the cutaneous microbiome of individual amphibians may play a role in susceptibility to the pathogen. In this study, twelve cave salamanders (Eurycea lucifuga) were collected. Cutaneous bacteria from each salamander were isolated and identified using Sanger Sequencing. Additionally, a Bd-challenge assay was performed to determine each isolate’s antifungal activity. Results indicated many microbial isolates possessed inhibitory capabilities against Bd, which may …

Molecular Mechanisms Underlying Mucosal Attachment And Colonization By Clostridioides Difficile, Ben Sidner

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacterium which causes gastrointestinal disease and is a leading cause of nosocomial infections. Although infection typically occurs following antibiotic therapy, in recent years there has been an increase in infections which are not preceded by antibiotic use. Additionally, community-associated infections and rates of disease recurrence have increased. While it is understood that a healthy gastrointestinal microbiota provides protection against infection, the molecular mechanisms which underly C. difficile's ability to colonize and persist in the gut are mostly unknown. Building on work from others that suggests C. difficile associates with the outer mucus …

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial cells. The proteins encoded …

Eskape Pathogens: The Clinical Prevalence And Molecular Mechanisms Of Antibiotic Resistance, Anusha Attre

Honors Scholar Theses

The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of all nosocomial, or healthcare-associated (HAI), infections (Navidinia, 2016). The purpose of this research study is to determine the burden of ESKAPE infections on healthcare and study the antibiotic resistance in these high-risk pathogens to provide direction for researchers to develop new antimicrobial innovations to reduce ESKAPE infectivity and improve patient outcomes. To study the burden of ESKAPE infections, this review analyzes the current statistics explaining the clinical prevalence of each pathogen in causing HAIs. Additionally, each pathogen is …

Impact Of Probiotics On Black Soldier Fly Larvae Transmission Of Stenotrophomonas Maltophilia, Emily Marie Mclaughlin

Honors College

Stenotrophomonas maltophilia is an opportunistic pathogen which can cause a variety of infections, especially in immunocompromised individuals. It has recently been found that black soldier flies can act as carriers for S. maltophilia (Callegari et al., 2020). I have investigated how probiotics impact their vector capabilities. Black soldier fly larvae have been fed substrate spiked with S. maltophilia. After several days of feeding, the larvae were investigated by PCR and plating (Sveensson-Stadler et al., 2011). Two groups of larvae were fed with potatoes infected with S. maltophilia. Persistence of S. maltophilia was determined using PCR by taking samples …

Editorial: Pathogens, Pathobionts, And Autoimmunity, Linda A. Spatz, Gregg J. Silverman, Judith A. James

Publications and Research

No abstract provided.

Mara Repression Of Virulence Gene Hila In Salmonella, Alexandra King, Lauren Daugherty, Lon Chubiz Phd

Undergraduate Research Symposium

Salmonella is a bacteria most commonly known for causing the eponymous food-related illness. Due to their rapid reproduction rate and their ability to be propogated and maintained in a lab setting, they are commonly used in lab studies so that we can better understand how Salmonella causes disease in organisms that are more difficult to study. One area of interest is analyzing how Salmonella controls expression of the mechanisms that actually cause disease, called virulence traits, in response to the environment. In this study, antibiotic stress was used to analyze virulence gene expression. MarA is a gene that regulates ampicillin …

Higher Entropy Observed In Sars-Cov-2 Genomes From The First Covid-19 Wave In Pakistan, Najia Karim Ghanchi, Asghar Nasir, Kiran I. Masood, Syed Hani Abidi, Syed Faisal Mahmood, Akber Kanji, Safina Abdul Razzak, Waqasuddin Khan, Saba Shahid, Maliha Yameen, Ali Raza, Javaria Ashraf, Zeeshan Ansar Ahmed, Mohammad Buksh Dharejo, Nazneen Islam, Zahra Hasan, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: We investigated the genome diversity of SARS-CoV-2 associated with the early COVID-19 period to investigate evolution of the virus in Pakistan.
Materials and methods: We studied ninety SARS-CoV-2 strains isolated between March and October 2020. Whole genome sequences from our laboratory and available genomes were used to investigate phylogeny, genetic variantion and mutation rates of SARS-CoV-2 strains in Pakistan. Site specific entropy analysis compared mutation rates between strains isolated before and after June 2020.
Results: In March, strains belonging to L, S, V and GH clades were observed but by October, only L and GH strains were present. The …

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 …

Microbial Screening Reveals Oral Site-Specific Locations Of The Periodontal Pathogen Selenomonas Noxia, Jaydene Mcdaniel, Steven Mcdaniel, Beanca Jhanine Samiano, Matthew Marrujo, Karl Kingsley, Katherine M. Howard

Dental Medicine Faculty Publications

Introduction: Selenomonas noxia (SN) is an important periodontal pathogen, associated with gingivitis and periodontitis. Many studies have found associations between SN and indicators of poor health outcomes, such as smoking, low socioeconomic status and obesity. However, less is known about the prevalence of this organism and more specifically about other oral site-specific locations that may harbor this organism. Methods: Using an existing patient repository (n = 47) of DNA isolated from saliva and other oral sites (n = 235), including the dorsum of the tongue, lower lingual incisor, upper buccal molar and gingival crevicular fluid (GCF), molecular screening for SN …

Prevalence And Risk Factors Associated With Multi-Drug Resistant Organisms (Mdro) Carriage Among Pediatric Patients At The Time Of Admission In A Tertiary Care Hospital Of A Developing Country. A Cross-Sectional Study, Sonia Qureshi, Noshi Maria, Mohammad Zeeshan, Seema Irfan, Farah Naz Qamar

Department of Paediatrics and Child Health

Background: The rise of Multidrug-resistant organisms (MDROs) poses a considerable burden on the healthcare systems, particularly in low-middle income countries like Pakistan. There is a scarcity of data on the carriage of MDRO particularly in the pediatrics population therefore, we aimed to determine MDRO carriage in pediatric patients at the time of admission to a tertiary care hospital in Karachi, Pakistan, and to identify the risk factors associated with it.
Methods: A cross-sectional study conducted at the pediatric department of Aga Khan University Hospital (AKUH) from May to September 2019 on 347 children aged 1-18 years. For identification of MDRO …

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.

Respiratory Pathogens In Patients With Acute Exacerbation Of Non-Cystic Fibrosis Bronchiectasis From A Developing Country, Shayan Shahid, Kausar Jabeen, Nousheen Iqbal, Joveria Farooqi, Muhammad Irfan

Medical College Documents

Bronchiectasis unrelated to cystic fibrosis (non-CF bronchiectasis) has become a major respiratory disease in developing nations. The dilated mucus filled airways promote bacterial overgrowth followed by chronic infection, bronchial inflammation, lung injury and re-infection Accurate pathogen identification and antimicrobial susceptibility allowing appropriate treatment, in turn, may break this vicious cycle. To study the spectrum and antimicrobial spectrum of pathogen yielded from respiratory specimens in adult patients with acute exacerbation of non-cystic fibrosis (CF) bronchiectasis. This cross-sectional study was performed at the pulmonology clinics of the Aga Khan University, Karachi, Pakistan from 2016-2019. Respiratory specimens were collected from adult patients with …

Molecular Surveillance Of Drug Resistance: Plasmodium Falciparum Artemisinin Resistance Single Nucleotide Polymorphisms In Kelch Protein Propeller (K13) Domain From Southern Pakistan, Najia Karim Ghanchi, Bushra Qurashi, Hadiqa Raees, Mohammad Asim Beg

Department of Pathology and Laboratory Medicine

Background: K13 propeller (k13) polymorphism are useful molecular markers for tracking the emergence and spread of artemisinin resistance in Plasmodium falciparum. Polymorphisms are reported from Cambodia with rapid invasion of the population and almost near fixation in south East Asia. The study describes single nucleotide polymorphisms in Kelch protein propeller domain of P. falciparum associated with artemisinin resistance from Southern Pakistan.
Methods: Two hundred and forty-nine samples were collected from patients with microscopy confirmed P. falciparum malaria attending Aga Khan University Hospital during September 2015-April 2018. DNA was isolated using the whole blood protocol for the QIAmp DNA Blood Kit. …

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

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 …

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 …

Carbapenem-Resistant Enterobacteriaceae (Cre): Epidemiology, Duration Of Carriage, And Progression To Infection In A Large Healthcare System In Miami, Fl, Adriana Jimenez

FIU Electronic Theses and Dissertations

Carbapenem-resistant Enterobacteriaceae (CRE) are multidrug-resistant organisms (MDRO) considered by the CDC as an urgent public health threat that is spreading globally. Little is known about the epidemiology of CRE in Miami, FL. The purpose of this dissertation was to 1) Evaluate trends in the epidemiology of CRE among patients admitted to the acute care facilities of the largest healthcare system in Miami, FL between 2012 and 2016, 2) Identify factors associated with progressing to infection among patients colonized with carbapenemase-producing Enterobacteriaceae (CPE), and 3) Determine the duration of CPE carriage and factors associated with long-term carriage in our cohort.

A …

Investigating Microbial And Host Factors That Modulate Severity Of Clostridioides Difficile Associated Disease, Armando Lerma

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Clostridioides difficile is recognized as one of the most important pathogens in hospital and community healthcare settings. The clinical outcome of infection of toxigenic C. difficile infection (CDI) ranges from asymptomatic colonization to fulminant pseudomembranous colitis and death. In recent studies, it has been suggested that a high proportion of nosocomial CDI cases are transmitted from asymptomatic carriers which might be acting as infection reservoirs. Understanding what causes the different responses to infection could lead to the development of novel prevention and treatment strategies. Although several explanations have been proposed to explain variations in susceptibility, understanding of the exact mechanisms …

Evaluation Of Semi-Quantitative Compared To Quantitative Cultures Of Tracheal Aspirates For The Yield Of Culturable Respiratory Pathogens - A Cross-Sectional Study, Salima Rattani, Joveria Farooqi, Ghazala Jabeen, Saeeda Chandio, Qaiser Kash, Aijaz Khan, Kauser Jabeen

Department of Pathology and Laboratory Medicine

Background: Diagnosis of lower respiratory tract infections (LRTI) depends on the presence of clinical, radiological and microbiological findings. Endotracheal suction aspirate (ETSA) is the commonest respiratory sample sent for culture from intubated patients. Very few studies have compared quantitative and semi-quantitative processing of ETSA cultures for LRTI diagnosis. We determined the diagnostic accuracy of quantitative and semi-quantitative ETSA culture for LRTI diagnosis, agreement between the quantitative and semi quantitative culture techniques and the yield of respiratory pathogens with both methods.
Methods: This was a cross-sectional study conducted at the Aga Khan University clinical laboratory, Karachi, Pakistan. One hundred and seventy-eight …

Contributions Of Gyra And Parc Mutations And Qnrs2 Acquisition To Ciprofloxacin Resistance In Aeromonas Veronii Hm21, Daniel J. Silverstein

Honors Scholar Theses

In recent years, ciprofloxacin resistant (CpR) Aeromonas veronii and A. hydrophila strains have been isolated from the wounds of patients receiving leech therapy. Genome comparisons of these CpR isolates revealed the presence of chromosomal mutations in gyrA and parC as well as the gain of qnrS2 on either a large, 34 kb, conjugatable, low-copy plasmid, pAv42, or on a small, 6.8 kb, high-copy plasmid, pAh1471. The minimum inhibitory concentration, MIC, for Cp of these clinical isolates ranged from 1 to ≥32 µg/mL and some harbored a qnrS2 containing plasmid. We wanted to assess the contributions of these factors in an …

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 …

Histidine-Triad Hydrolases Provide Resistance To Peptide-Nucleotide Antibiotics., Eldar Yagmurov, Darya Tsibulskaya, Alexey Livenskyi, Marina Serebryakova, Yury I Wolf, Sergei Borukhov, Konstantin Severinov, Svetlana Dubiley

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The Escherichia coli microcin C (McC) and related compounds are potent Trojan horse peptide-nucleotide antibiotics. The peptide part facilitates transport into sensitive cells. Inside the cell, the peptide part is degraded by nonspecific peptidases releasing an aspartamide-adenylate containing a phosphoramide bond. This nonhydrolyzable compound inhibits aspartyl-tRNA synthetase. In addition to the efficient export of McC outside the producing cells, special mechanisms have evolved to avoid self-toxicity caused by the degradation of the peptide part inside the producers. Here, we report that histidine-triad (HIT) hydrolases encoded in biosynthetic clusters of some McC homologs or by standalone genes confer resistance to McC-like …