Microbiology Commons^™

Host-Pathogen Dynamics Underpinning Staphylococcus Aureus Growth During Intracellular Osteoclast Infection, Luke D. O'Connor

WUSM Theses and Dissertations – All Programs

Bone infection is most commonly caused by the gram-positive bacterium Staphylococcus aureus. It has myriad ways in which it can circumvent or subvert killing by the host or antibiotics. Intracellular infection is one such niche that is protective from immune and antibiotic attack. In 2019, Krauss and colleagues discovered that infected osteoclasts (OCs) allow S. aureus to replicate intracellularly. There they found that the ability of S. aureus to grow inside the cell was tied to OC differentiation. The magnitude of overnight bacterial expansion positively correlated with OC maturity and duration cultured with the osteoclastogenic factor RANK ligand (RANKL). Bacterial …

Dual-Action Antibacterial Agents Targeting Biofilm Reduction And Membrane Disruption In Staphylococcus Aureus, Rahmat Folashade Zakariyah, Waliyullahi Akorede Husain, Elohor Precious Samuel, Wonder Olanipekun Oloruntoba, Fatmah Opeyemi Saka, Khalid Ayinde Oyelami, Mariam Temitope Baker

Al-Bahir

Antimicrobial resistance in Staphylococcus aureus is a serious global health problem as the organism rapidly develops resistance against widely used antibiotics. This study sought to investigate the antibacterial and antibiofilm properties of γ-Tocopherol, a natural compound from Ocimum gratissimum, as well as its synergism with 5-hydroxymethylfurfural (5-HMF) against S. aureus. The antibacterial activities and minimum inhibitory concentrations of the compounds were determined using agar diffusion and microbroth dilution methods, respectively. Biofilm reduction was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) assay and membrane integrity was evaluated using the crystal violet microtiter plate assay and the ion leakage assay. The results …

Characterization Of Staphylococcus Aureus Clinical Isolates From Deep Musculoskeletal Infections For An In Vitro Biofilm Model For Phage Therapy, Raquel C. Luna

Dissertations and Theses (Open Access)

The rise of multidrug-resistant (MDR) infections is a growing concern in the treatment of deep musculoskeletal infections (MSKIs) and orthopaedic device-related infections (ODRIs). Staphylococcus aureus is responsible for about one third of these infections due to its strong biofilm forming capacity, presence on human skin, and the large number of antibiotic-resistant variants. Bacteriophage (phage) therapy is now being considered as a treatment for MDR MSKIs/ODRIs. We are investigating the use of phage encapsulated into or adsorbed onto biodegradable microspheres for local delivery to the site of these MDR infections. We determined that the anti-staphylococcal phage K effectively lyses the S. …

Nasal Microbionts Differentially Colonize And Elicit Cytokines In Human Nasal Epithelial Organoids, Andrea I Boyd, Leah A Kafer, Isabel F Escapa, Amal Kambal, Hira Tariq, Susan G Hilsenbeck, Hoa Nguyen-Phuc, Anubama Rajan, Joshua M Lensmire, Kathryn A Patras, Pedro A Piedra, Sarah E Blutt, Katherine P Lemon

Faculty, Staff and Students Publications

Nasal colonization by Staphylococcus aureus or Streptococcus pneumoniae is associated with an increased risk of infection by these pathobionts, whereas nasal colonization by Dolosigranulum species is associated with health. Human nasal epithelial organoids (HNOs) differentiated at air-liquid interface (ALI) physiologically recapitulate human nasal respiratory epithelium with a robust mucociliary blanket. Due to their natural stem-like properties, HNO lines are a long-term experimental resource that offers genetic diversity based on the different donors. To develop HNOs as a new model system for bacterial nasal colonization, we reproducibly monocolonized HNOs differentiated at ALI with S. aureus, S. pneumoniae, or Dolosigranulum …

Exploring The Antagonistic Polymicrobial Interaction Of Alcaligenes Faecalis With Prokaryotic And Eukaryotic Microorganisms, Aly Hargrave

Electronic Theses and Dissertations

Alcaligenes faecalis, a generally nonpathogenic, Gram-negative bacterium, has been observed by our laboratory to possess antagonistic activity against antimicrobial-resistant genera Staphylococcus, Candida, and Bacillus. This study focused on exploring the inhibition mechanism of A. faecalis against the three genera, with an emphasis on S. aureus. A library of A. faecalis transposon mutants was constructed and identified fourteen possible genetic factors linked to this inhibitory activity. Characterization of this inhibition indicated that A. faecalis suppressed S. aureus planktonic and biofilm growth via a contact-dependent mechanism, with pronounced effects during biofilm attachment phase. In a Caenorhabditis elegans …

A Multi-Tiered Approach To Improving Vaccination: Adjuvanticity, Alternate Routes Of Delivery, And Science Communication, Haley Agnes Bridgewater

Boise State University Theses and Dissertations

Vaccines have been used to prevent infectious disease for over 200 years. While they are an incredible way to prevent loss of life, they can be improved upon. Researchers around the globe are working to improve the immune response and ultimately the protection provided by existing and new vaccines. In this dissertation, I investigate three ways to improve vaccine immune responses: using an adjuvant, using a prime-boost intramammary delivery route in cows, and using microneedle delivery route. Cholera toxin (CT) is a bacterial toxin that has a non-toxic B subunit (CTB) used as a vaccine adjuvant. However, little is known …

Clinical Characteristics And Outcomes Of Pediatric Staphylococcal Scalded Skin Syndrome (Ssss) At An Inner-City Tertiary Care Center, Nina Kb Gust Md, Ashley Frei Bs, Rebecca M. Adams Bs, Elika Ridelman Phd, Christina Shanti Md, Ronald Thomas Phd, Jocelyn Y. Ang Md

Medical Student Research Symposium

Introduction

Staphylococcal Scalded Skin Syndrome (SSSS) is a blistering skin condition caused by a toxin-producing staphylococcus species. Epidemiologic studies on pediatric SSSS in the United States are limited, with a reported incidence of 7.67 cases per million children and 45.1 per million infants. Immature renal function, lack of protective antibodies, and increased exotoxin target desmoglein-1 are hypothesized to increase incidence in younger children. We aimed to determine clinical and microbiological characteristics of pediatric SSSS and factors that could help predict disease severity.

Methods

A retrospective chart review was performed for admitted patients under 18 years old diagnosed with SSSS from …

The Impact Staphylococcus Aureus Has On Conventional And Organic Dairy Herds In New Hampshire And New York, Jacqueline Rose Holmes

Honors Theses and Capstones

Staphylococcus aureus is a potentially virulent bacterium that causes mastitis in dairy cattle. The toxins produced from S. aureus impact host immunity, damage the mammary gland, and can adapt to cause antimicrobial resistance. It is important to manage both organic and conventional farms correctly by practicing proper hygiene while milking and providing a clean environment. There is a significant increase of S. aureus cases on organic farms compared to conventional, so there may be ways in which organic management and treatment options could be altered to reduce economic loss and animal suffering. The thesis focuses on the involvement S. aureus …

Investigating Antimicrobial Efficacy Of Turmeric And Rosemary Oil Against Staphylococcus Aureus, Aishwarya Tripathi

Selected Full-Text Master Theses 2021-

This study investigates the antimicrobial efficacy of turmeric (Curcuma longa) and rosemary essential oil (Rosmarinus officinalis) against Streptococcus aureus, with a comparative analysis to phenoxyethanol, a widely used synthetic preservative. The growing consumer demand for natural cosmetic formulations have intensified the search for plant-derived alternatives to synthetic preservatives. Turmeric and rosemary oil were selected based on their documented antimicrobial, antioxidant, and anti-inflammatory properties. The objective of this research was to evaluate whether these natural agents can serve as effective preservatives in topical gel formulations, either individually or in combination, and how their efficacy compares to phenoxyethanol.

Eight gel-based formulations were …

Tetr Family Regulator, Farr, Influences Rot-Mediated Control Of Virulence Factor Expression In Staphylococcus Aureus, Julia C. Schumacher

USF Tampa Graduate Theses and Dissertations

Point-mutation variants of the TetR family regulator, FarR, have emerged across Staphylococcus aureus sequence types as conferring antibiotic and fatty acid resistance, particularly in Hospital-Associated Methicillin Resistant S. aureus (HA-MRSA) strains. FarR also exhibits an additional largely uncharacterized relationship to virulence factor production, seemingly through the global repressor of toxins—Rot, which functions to regulate S. aureus’ ability to colonize and persist in the host via a complex cascade of signaling. While Rot protein is post-transcriptionally regulated by the highly characterized Agr system, there is little known about its transcriptional regulation. Herein, we explored these dynamics by initially characterizing virulence phenotypes …

Staphylococcus Aureus Oleate Hydratase Produces Ligands That Activate Host Ppara, Christopher D. Radka, Matthew W. Frank, Tyler S. Simmons, Cydney N. Johnson, Jason W. Rosch, Charles O. Rock

Markey Cancer Center Faculty Publications

Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10- hydroxyoctadecanoic acid (h18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264.7 macrophage cell line and mouse primary bone marrow-derived …

Probiotic Compounds Inhibit Staphylococcus Aureus Biofilm Formation, Reduce Virulence, & Improve Antibiotic Sensitivity, Kyle R. Leistikow

Dissertations (1934 -)

Multidrug-resistant (MDR) bacterial infections are a top five global public health threat, causing 2.8 million infections and 35,000 deaths annually in the US alone. Staphylococcus aureus is one of the most clinically important MDR pathogens in the world with infections leading to high rates of morbidity and mortality in both humans and animals. This bacterium's ability to form protective biofilms further complicates classical antibiotic interventions, highlighting the need for new therapeutics with novel mechanisms of action. The goal of this dissertation was to investigate antibiofilm mechanisms employed by probiotic bacteria to reduce S. aureus virulence and mitigate antimicrobial resistance evolution …

Trends In Antibiotic Susceptibility Of Staphylococcus Aureus Isolates In A Pediatric Hospital: An Analysis Of The Impact Of The Sars-Cov-2 Pandemic, Juan Miguel S. Gonzalez Rivero

Honors Undergraduate Theses

Infections caused by the organism Staphylococcus aureus are one of the most common causes for community-associated and healthcare-acquired infections (HAI). Isolates of this bacterium found within the healthcare setting often demonstrate a higher prevalence of antibiotic resistance making these infections difficult to treat. Historically, considerable focus has been placed on methicillin-resistant S. aureus (MRSA), which are strains resistant to β-lactam antibiotics like penicillin, oxacillin and cephalosporins; however, methicillin-sensitive (MSSA) strains may also possess resistance to several first-line antibiotics. Resistance to antibiotics can be acquired through horizontal gene transfer (HGT) by means of mobile genetic elements or by random DNA mutations …

Investigating Structural And Biochemical Characteristics Of A Peptidase Required For Staphylococcus Aureus Virulence, Sagar Bhusal

Master's Theses

Staphylococcus aureus is an opportunistic Gram-positive pathogen that transiently colonizes 30% of the population at any given time. Upon breaching host skin or mucosal barriers, S. aureus can infect and cause disease in nearly all host tissues. Once inside the host, S. aureus expresses a plethora of virulence factors, mostly regulated by the Accessory Gene Regulatory (Agr) quorum sensing system, which facilitates the evasion of immune responses or directly promotes pathogenesis. The S. aureus Agr system relies on the production of a small peptide known as an auto-inducing peptide (AIP) to control virulence gene expression in response to cell density. …

Death Of A Bacterium: Exploring The Inhibition Of Staphylococcus Aureus By Burkholderia Cenocepacia., Tiffany Brandt

Electronic Theses and Dissertations

Antimicrobial resistance is a phenomenon of increasing concern as antimicrobial overuse and misuse eliminate current therapeutic options, ushering society into a post-antimicrobial era. Antibiotic discovery and synthesis efforts are urgently needed to counter the increasing burden of antimicrobial resistance. Staphylococcus aureus is a causative agent of a variety of clinical manifestations including bacteremia, endocarditis, soft tissue infection, osteomyelitis, and device-related infections. S. aureus infection presents additional treatment challenges due to its capacity for biofilm formation, which is a mode of growth that confers protection from antibiotics and physical elimination, and the emergence of antibiotic resistant strains, including methicillin-resistant S. aureus …

To Be Or Not To Be: A Tale Of Staphylococcal Gpsb, Lauren R. Hammond

USF Tampa Graduate Theses and Dissertations

There are two big drivers motivating studies into bacterial cell division. The first is a desire to understand life around us. One of the defining characteristics of life is the ability for a cell to grow and divide, and without in-depth knowledge of this process, we cannot truly understand the complexities that allow for life on this planet. The second motivator is to identify new drug targets in the ongoing fight against antimicrobial resistance. Many infectious organisms have become resistant to commonly used antibiotics, and the bacterial cell division machinery is a largely untapped essential process with many potential therapeutic …

Delineating The Role Of The Msaabcr Operon In Staphylococcal Overflow Metabolism, Gc Bibek, Gyan S. Sahukhal, Mohamed O. Elasri

Faculty Publications

Staphylococcus aureus is an important human pathogen that can infect almost every organ system, resulting in a high incidence of morbidity and mortality. The msaABCR operon is an important regulator of several staphylococcal phenotypes, including biofilm development, cell wall crosslinking, antibiotic resistance, oxidative stress, and acute and chronic implant-associated osteomyelitis. Our previous study showed that, by modulating murein hydrolase activity, the msaABCR operon negatively regulates the proteases that govern cell death. Here, we report further elucidation of the mechanism of cell death, which is regulated by the msaABCR operon at the molecular level in the USA300 LAC strain. We showed …

Identifying Causative Microorganisms In Left Ventricular Assist Device Infections As A Guide For Developing Bacteriophage Therapy, Ishan Kamat, Harveen Lamba, Casey Hines-Munson, Samuel Hudson, Kenneth Liao, Kenneth L Muldrew, Sabrina Green, Austen Terwilliger, Heidi B Kaplan, Robert F Ramig, Anthony Maresso, Barbara W Trautner

Faculty, Staff and Students Publications

BACKGROUND: As more left ventricular-assist devices (LVADs) are implanted, multidrug-resistant LVAD infections are becoming increasingly common, partly due to bacterial biofilm production. To aid in developing bacteriophage therapy for LVAD infections, we have identified the most common bacterial pathogens that cause LVAD driveline infections (DLIs) in our heart transplant referral center.

MATERIALS AND METHODS: We studied a retrospective cohort of patients who received LVADs from November 2003 to August 2017 to identify the common causative organisms of LVAD infection. We also studied a prospective cohort of patients diagnosed with DLIs from October 2018 to May 2019 to collect bacterial strains …

Inhibition Of Staphylococcus Aureus Biofilm By Variovorax Paradoxus, Esther Gomez

University of the Pacific Theses and Dissertations

Staphylococcus aureus is one of the leading causes of fatal nosocomial infections. Often, S. aureus can grow as a biofilm which protects the population from the surrounding environment. Strains of S. aureus are resistant to virtually all known antibiotics on the market. Variovorax paradoxus is a soil microbe with many unusual metabolic activities. It has been previously observed that, V. paradoxus can inhibit the growth of S. aureus when in co-culture. In this work we report on inhibition of S. aureus biofilm formation by V. paradoxus due to a suspected inhibitory soluble factor.

A Functional Characterization Of The Omega (Ω) Subunit Of Rna Polymerase In Staphylococcus Aureus, Shrushti B. Patil

USF Tampa Graduate Theses and Dissertations

In bacteria, RNA polymerase (RNAP) is a well-characterized and highly conserved multi-subunit enzyme complex responsible for transcription of DNA into RNA. The ω subunit (rpoZ/RpoZ), one of the smaller accessory subunits of RNAP, is often overlooked and under-studied, however, particularly in Gram-positive species. We have previously shown that deleting ω impacts the integrity of RNA polymerase in S. aureus, especially the β' subunit, and alters preference of the core enzyme for sigma factors, skewing heavily towards σB instead of the housekeeping σ factor. Consequently, this causes deregulation of myriad transcriptional processes, strongly rewiring gene expression circuits, and ultimately impairing the …

The Staphylococcus Aureus Lrgab Operon Encodes A Holin-Like Protein Involved In Pyruvate Transport, Jennifer L. Endres

Theses & Dissertations

The Staphylococcus aureus cidABC and lrgAB operons encode a well-conserved family of proteins involved in programmed cell death (PCD) during biofilm development. Based on the structural similarities that CidA and LrgA share with bacteriophage holins, we have hypothesized that these proteins function by forming pores within the cytoplasmic membrane. To test this, we utilized a “lysis cassette” system that demonstrated the abilities of the cidA and lrgA genes to support bacteriophage endolysin-induced cell lysis. In addition, the CidA and LrgA proteins were shown to localize to the surface of membrane vesicles and cause leakage of small molecules, providing direct evidence …

Elucidating The Relationship Between Recombination Frequency And Antibiotic Resistance In Staphylococcus Aureus, Joseph R. Matthews

Legacy Theses & Dissertations (2009 - 2024)

Staphylococcus aureus is a common commensal and opportunistic pathogen of humans. It causes a variety of diseases, ranging from skin and soft infections to life-threatening invasive diseases. Many strains of S. aureus have developed resistance to a variety of antibiotic classes, including many beta-lactams. The evolution and dissemination of antibiotic resistance in S. aureus lay in large part to its remarkable ability of acquiring DNA from other organisms through horizontal gene transfer and recombination. In this study, I elucidated the relationship between frequencies of recombination events and horizontally acquired antibiotic resistant genes in a population of S. aureus sampled from …

Transcriptomic And Functional Investigation Of Bacterial Biofilm Formation, Brooke R. Nemec

USF Tampa Graduate Theses and Dissertations

Staphylococcus aureus and Acinetobacter baumannii are two highly successful human pathogens, which have adopted very different, but effective survival strategies. The success of S. aureus is attributed to the tight regulation of an arsenal of virulence factors. Conversely, A. baumannii lacks what would be considered traditional virulence factors and, instead, has developed a high tolerance for environmental stress, which allows it to persist in unforgiving environments, including nosocomial settings and the human body. One common characteristic of these two organisms is their proclivity for biofilm formation. Herein, we discuss the diverse mechanisms governing biofilm formation for A. baumannii and S. …

Elucidating The Role Of The Msaabcr Operon In Persister Cells Formation And Stress Response In Staphylococcus Aureus, Shanti Pandey

Dissertations

Staphylococcus aureus is a major human pathogen that causes lethal systemic conditions such as infective endocarditis, osteomyelitis, sepsis and pneumonia. Chronic in nature, these diseases are often refractory to the antibiotic treatment. Such recalcitrance is mainly caused due to the presence of persister cells, which are a bacterial subpopulation that exhibits extreme, yet transient antibiotic tolerance accompanied by a transient halt in the growth. However, upon cessation of antibiotic treatment, resumption in growth of persister cells causes recurrence of infections and treatment failure, displaying tremendous clinical significance. In this study, we show the involvement of the msaABCR operon in persister …

Study Of The Role Of The Msaabcr Operon In Tricarboxylic Acid Cycle Activity And Persister Cell Formation In Staphylococcus Aureus, Karsen Motter

Honors Theses

Staphylococcus aureus is an important human pathogen that causes wide arrays of infections ranging from minor skin infections to lethal systemic conditions such as infective endocarditis, osteomyelitis, sepsis and pneumonia. These systemic diseases are often difficult to treat due to the presence of persister cells. Persister cells are a phenotypic variant of the bacterial population that exhibit extreme and transient antibiotic tolerance accompanied by a transient halt in growth. Upon cessation of antibiotic treatment, however, persisters resume growth which results in recurrence of infections. This characteristic of persister cells therefore displays high clinical significance. In this study, we show the …

Interregulation Between Msaabcr Operon And Ccpe To Determine Staphylococcal Metabolism And Virulence, Erin R. Cox

Honors Theses

Staphylococcus aureus is a complex human pathogen that causes problems in both healthcare and community settings. Staphylococcus aureus is a gram-positive, sphere shaped bacterium that usually colonizes in the nasal cavity of healthy individuals. Staphylococcus aureus infections are a growing health concern due to its ability to produce virulence factors, such as pigmentation, protease production, and capsule formation. Two regulators in S. aureus virulence factors are msaABCR, which is a newly characterized operon, and ccpE. In order to determine the interaction between these two regulators in regulating virulence and metabolism in S. aureus, ccpE and ccpE/ …

Increasing The Frequency Of Periodic Spatial Disturbance Decreases Surface Attachment Protein Expression In Staphylococcus Aureus, Ivana M. Barraza

All HCAS Student Capstones, Theses, and Dissertations

Staphylococcus aureus is an opportunistic pathogen that can cause a variety of acute and chronic illnesses. The severity of these illnesses such as sepsis, necrotizing pneumonia, and toxic shock syndrome is measured through the virulence that S. aureus inflicts on its host. Methicillin-resistant S. aureus (MRSA) is commonly associated with secondary infections and is challenging to treat given the limited selection of antibiotics that are effective against it. Accordingly, novel approaches to reduce S. aureus pathogenicity are required. S. aureus regulates pathogenesis through a cell-to-cell communication system referred to as quorum sensing. Effective communication determines the production of two broad …

The Msaabcr Operon Regulates Persister Formation By Modulating Energy Metabolism In Staphylococcus Aureus, Shanti Pandey, Gyan S. Sahukhal, Mohamed O. Elasri

Faculty Publications

Staphylococcus aureus is a major human pathogen that causes chronic, systemic infections, and the recalcitrance of these infections is mainly due to the presence of persister cells, which are a bacterial subpopulation that exhibits extreme, yet transient, antibiotic tolerance accompanied by a transient halt in growth. However, upon cessation of antibiotic treatment, a resumption in growth of persister cells causes recurrence of infections and treatment failure. Previously, we reported the involvement of msaABCR in several important staphylococcal phenotypes, including the formation of persister cells. Additionally, observations of the regulation of several metabolic genes by the msaABCR operon in transcriptomics and …

Investigating The Roles Of Lipids In Staphylococcus Aureus Infection, Xi Chen

Dissertations

The Gram-positive bacterium Staphylococcus aureus is a major threat to public health and causes a multitude of infections, ranging from mild skin and soft infection, to more severe diseases including sepsis, osteomyelitis and infective endocarditis. As a successful pathogen, S. aureus employs various mechanisms to invade host tissues, evade immune responses, and survive in the host environment. One critical adaptive trait of S. aureus that promotes virulence and survival is the ability to maintain membrane homeostasis via flexible modifications to its lipid composition in response to the surrounding lipid environment. Phospholipids are the major component of the bacterial membrane and …

The Role Of The Msaabcr Operon In Implant-Associated Chronic Osteomyelitis In Staphylococcus Aureus Usa300 Lac, Gyan S. Sahukhal, Michelle Tucci, Hamed Benghuzzi, Gerri Wilson, Mohamed O. Elasri

Faculty Publications

The msaABCR operon regulates several staphylococcal phenotypes such as biofilm formation, capsule production, protease production, pigmentation, antibiotic resistance, and persister cells formation. The msaABCR operon is required for maintaining the cell wall integrity via affecting peptidoglycan cross-linking. The msaABCR operon also plays a role in oxidative stress defense mechanism, which is required to facilitate persistent and recurrent staphylococcal infections. Staphylococcus aureus is the most frequent cause of chronic implant-associated osteomyelitis (OM). The CA-MRSA USA300 strains are predominant in the United States and cause severe infections, including bone and joint infections.