Bryan H Bellaire

Iowa State University | ISU · Department of Veterinary Microbiology and Preventive Medicine

Mycobacterium marinum is a waterborne pathogen responsible for tuberculosis-like infections in cold-blooded animals and is an opportunistic pathogen in humans. M. marinum is the closest genetic relative of the Mycobacterium tuberculosis complex and is a reliable surrogate for drug susceptibility testing. We synthesized and evaluated two nanoparticl...

The potential infectivity of SARS-CoV-2 in animals raises a public health and economic concern, particularly the high susceptibility of white-tailed deer (WTD) to SARS-CoV-2. The disparity in the disease outcome between humans and WTD is very intriguing, as the latter are often asymptomatic, subclinical carriers of SARS-CoV-2. To date, no studies h...

Human coronavirus (HCoV)-NL63 is an important contributor to upper and lower respiratory tract infections, mainly in children, while severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, can cause lower respiratory tract infections, and more severe, respiratory and systemic disease, which leads to fatal co...

The Coronaviridae family hosts various coronaviruses responsible for many diseases, from the common cold, severe lung infections to pneumonia. SARS-CoV-2 was discovered to be the etiologic agent of the Coronavirus pandemic, and numerous basic and applied laboratory techniques were utilized in virus culture and examination of the disease. Understand...

Nanoparticle carriers can improve antibiotic efficacy by altering drug biodistribution. However, traditional screening is impracticable due to a massive dataspace. A hybrid informatics approach was developed to identify polymer, antibiotic, and particle determinants of antimicrobial nanomedicine activity against Burkholderia cepacia, and to model n...

Antimicrobial resistance is a serious challenge facing human and veterinary health. Current methods of detecting resistance are limited in turn-around time or universal detection. In this work, a new antimicrobial susceptibility test is developed and validated, which utilizes deuterium labeling of membrane lipids to track the growth of bacterial ce...

The application of antiviral coatings to masks and respirators is a potential mitigating step toward reducing viral transmission during the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic. The use of appropriate masks, social distancing, and vaccines is the immediate solution for limiting the viral spread and protecting people...

Copper alloys are known for their high antimicrobial efficacy. Retrofitting high-touch surfaces in public space with solid copper components is expensive and often impractical. Directly coating copper onto these high-touch surfaces can be achieved with hot or cold spray, but the procedure is complicated and requires special equipment. This article...

The ability of SARS-CoV to infect different species, including humans, dogs, cats, minks, ferrets, hamsters, tigers, and deer, pose a continuous threat to human and animal health. Pigs, though closely related to humans, seem to be less susceptible to SARS-CoV-2. Former in vivo studies failed to demonstrate clinical signs and transmission between pi...

Antisense peptide nucleic acids (PNAs) have yet to translate to the clinic because of poor cellular uptake, limited solubility, and rapid elimination. Cell-penetrating peptides (CPPs) covalently attached to PNAs may facilitate clinical development by improving uptake into cells. We report an efficient technology that utilizes a fully automated fast...

Bacillus anthracis, the causative agent of anthrax, continues to be a prominent biological warfare and bioterrorism threat. Vaccination is likely to remain the most effective and user-friendly public health measure to counter this threat in the foreseeable future. The commercially available AVA BioThrax vaccine has a number of shortcomings where im...

Intestinal organoids can be used as an ex vivo epithelial model to study different drug delivery effects on epithelial cells’ luminal surface. In this study, the impact of surface charge on the delivery of 5-ASA loaded PLGA nanoparticles into the lumen of organoids was investigated. Alginate and chitosan were used to coat the nanoparticles and prov...

Antibiotics are critically important for treating microbial infections. Conventional antibiotics are intrinsically compromised by risk of cultivating antimicrobial resistance, poor bioavailability, toxicity, frequent dosing regimens, and poor patient compliance. Physiological barriers are an important driver of many of these shortcomings. Nanoscale...

A novel betacoronavirus (SARS-CoV-2) that causes severe pneumonia emerged through zoonosis in late 2019. The disease, referred to as COVID-19, has an alarming mortality rate and it is having a devastating effect on the global economy and public health systems. A safe, effective vaccine is urgently needed to halt this pandemic. In this study, immuno...

Peptide nucleic acids (PNAs) are charge-neutral oligonucleotides with emerging potential for treatment of genetic, acquired, and viral diseases, including COVID-19. Their challenging synthesis, however, limits their use for rapid therapeutic intervention and widespread application. Here, we report a highly efficient technology that utilizes a fully...

Yersinia pestis, the causative agent of pneumonic plague, induces a highly lethal infection if left untreated. Currently, there is no FDA-approved vaccine against this pathogen; however, USAMRIID has developed a recombinant fusion protein, F1-V, that has been shown to induce protection against pneumonic plague. Many F1-V-based vaccine formulations...

Vitamin C (ascorbic acid) and vitamin B3 (niacin) have been extensively studied since the 20th century. In the area of stem cell biology, vitamin C has shown its direct impact towards homeostasis and epigenetic changes.¹ Vitamin B3 aids in maintaining healthy intestinal homeostasis and reducing gut inflammation by participating in the rapamycin sig...

Drug delivery vehicles can improve the functional efficacy of existing antimicrobial therapies by improving biodistribution and targeting. A critical property of such nanomedicine formulations is their ability to control the release kinetics of their payloads. The combination of (and interactions among) polymer, drug, and nanoparticle properties gi...

We report that the gold containing anti-rheumatoid drug auranofin is amoebicidal against human pathogenic Naegleria fowleri. Treatment of N. fowleri cultures at biologically relevant concentrations of 0.75 µg/ml to 3.0 µg/ml auranofin reduced amoeba counts, metabolic activity and increased cell permeability. These results suggest that the addition...

We report that the gold containing anti‐rheumatoid drug auranofin is amoebicidal against human pathogenic Naegleria fowleri. Treatment of N. fowleri cultures at biologically relevant concentrations of 0.75 μg/ml to 3.0 μg/ml auranofin reduced amoeba counts, metabolic activity and increased cell permeability. These results suggest that the addition...

New therapies are needed to treat chronic bacterial diseases and intracellular pathogens, in particular, are very difficult to manage. The use of nanotherapeutics represents an approach to exploit size and charge of biological membranes to overcome barriers for treatment of intracellular pathogens including Brucella melitensis. In this work, polyan...

Compound semiconductor nanomaterials, such as telluride nanowires, nanorods, and nanoparticles, have many unique properties for wide range of potential applications. The interaction between organoids (a biological system) and telluride nanowires is a crucial research area for human health in terms of its safety concerns. In this study, we demonstra...

Inflammatory bowel disease (IBD) causes inflammation to the gastrointestinal tract. Local administration of Anti-inflammatory drugs such as 5-aminosalysilic acid (5-ASA) can alleviate the symptoms of IBD. The application of nanoparticles for IBD treatment in direct rectal administration showed high drug availability and treatment efficacy. However,...

Within infected host cells, mammalian orthoreovirus (MRV) forms viral factories (VFs), which are sites of viral transcription, translation, assembly, and replication. The MRV nonstructural protein μNS comprises the structural matrix of VFs and is involved in recruiting other viral proteins to VF structures. Previous attempts have been made to visua...

Within infected host cells, mammalian orthoreovirus (MRV) forms viral factories (VFs) which are sites of viral transcription, translation, assembly, and replication. MRV non-structural protein, μNS, comprises the structural matrix of VFs and is involved in recruiting other viral proteins to VF structures. Previous attempts have been made to visuali...

Rational design of adjuvants and delivery systems will promote development of next-generation vaccines to control emerging and re-emerging diseases. To accomplish this, understanding the immune enhancing properties of new adjuvants relative to those induced by natural infections can help with the development of pathogen mimicking materials that wil...

Polyanhydride nanoparticles have emerged as a versatile delivery platform, due to their ability to encapsulate diverse drugs, immunogens, antibodies, and proteins. However, mechanistic studies on the effects of particle chemistry interactions with immune cells have yet to be described. Understanding the mechanism by which these particles are intern...

Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a therapeutic approach that shows promise in the tre...

Neutrophil extracellular traps (NETs) are webs of DNA and protein with both anti-microbial and pro-thrombotic properties which have not been previously reported in dogs. To confirm dog neutrophils can form NETs, neutrophils were isolated from healthy dogs, and stimulated in vitro with 2μM, 8μM, 31μM, and 125μM platelet activating factor (PAF) or 0....

Complex biological barriers are major obstacles for preventing and treating disease. Nano-carriers are designed to overcome such obstacles by enhancing drug delivery through physiochemical barriers and improving therapeutic indices. This review critically examines both biological barriers and nano-carrier payloads for a variety of drug delivery app...

The invention provides compositions and methods to treat microbial infections in animals, to inhibit the replication of microbes in infected cells, and to kill pathogens in infected cells. The methods can include administering to an animal in need of such treatment an effective antimicrobial amount of a composition comprising polyanhydride micropar...

Footpad infection of C3HeB/FeJ mice with Leishmania amazonensis leads to chronic lesions accompanied by large parasite loads. Co-infecting these animals with L. major leads to induction of an effective Th1 immune response that can resolve these lesions. This cross-protection can be recapitulated in vitro by using immune cells from L. major-infected...

Leishmania amazonensis infection promotes alteration of host cellular signaling and intracellular parasite survival, but specific mechanisms are poorly understood. We previously demonstrated that L. amazonensis infection of dendritic cells (DC) activated extracellular signal-regulated kinase (ERK), a MAP-kinase kinase kinase, leading to altered DC...

Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful an...

Nanoparticles and microparticles made from polyanhydrides have been demonstrated to act effectively as vaccine adjuvants and drug delivery platforms. Amphiphilic polyanhydrides are excellent candidates for vaccine delivery because of their ability to: stabilize and protect fragile antigens; provide a sustained release of antigen; and modulate the i...

Innovative vaccine delivery platforms can facilitate the development of effective single-dose treatment regimens to control emerging and re-emerging infectious diseases. Polyanhydride microparticles are promising vaccine delivery vehicles due to their ability to stably maintain antigens, provide tailored release kinetics and function as adjuvants....

Canine brucellosis is a reportable zoonotic disease that can lead to canine reproductive losses and human infection through contact with infected urine or other genitourinary secretions. Although many locations require testing and euthanasia of positive dogs, current diagnosis is limited by the time required for seroconversion, for example, presenc...

An imminent need exists to design improved adjuvants and vaccines to control emerging and re-emerging diseases. An ideal vaccine will mimic the way in which a naturally occurring infection induces a robust immune response yet avoids the undesirable effects of disease. To accomplish this, new adjuvants must engage pattern recognition receptors on an...

Nanoparticulate systems have emerged as valuable tools in vaccine delivery through their ability to efficiently deliver cargo, including proteins, to antigen presenting cells. Internalization of nanoparticles (NP) by antigen presenting cells is a critical step in generating an effective immune response to the encapsulated antigen. To determine how...

Abstract Previous works demonstrated that various species of Leishmania promastigotes exhibit differential sensitivity to complement-mediated lysis (CML) during development. Upon exposure to normal human serum (NHS), cultures of Leishmania chagasi promastigotes recently isolated from infected hamsters (less than 5 in vitro passages) are CML-sensiti...

An imminent need exists to design improved adjuvants and vaccines to control emerging and re-emerging diseases. An ideal vaccine will mimic the way in which a naturally occurring infection induces a robust immune response yet avoids the undesirable effects of disease. To accomplish this, new adjuvants must engage pattern recognition receptors on an...

Brucella spp. are highly adapted intracellular pathogens of mammals that cause chronic infections while surving and replicating in host monocytes and macrophages. Although monocytes are normally susceptible to infection, pretreatment with pro-inflammatory cytokine interferon-γ (IFN-γ) activates cellular defense mechanisms that increase intracellula...

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...

An opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. This study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimick...

Supplementary Data Table

The natural infection of a pathogen stimulates a protective and enduring immune response. Thus, an ideal approach to vaccine design is to mimic the immune response associated with a natural infection while avoiding the undesirable side effects of the disease. Vaccines have proven to be the most effective method of preventing infectious diseases, ye...

Polyanhydride particles elicit unique cellular responses from immune cells by stimulating particle internalization and by directing intracellular trafficking. Through encapsulating antibiotics within the polyanhydride particles we can achieve sustained release of the antimicrobial compounds. The chemistry of the polymer and particle size can be alt...

The natural infection of a pathogen stimulates a protective and enduring immune response. Thus, an ideal approach to vaccine design is to mimic the immune response associated with a natural infection while avoiding the undesirable side effects of the disease. Vaccines have proven to be the most effective method of preventing infectious diseases, ye...

Improving efficacy of subunit-based immunization protocols without eliciting adverse reactions continues to be a hurdle in vaccine design. Vaccination of mice in our laboratory with surface eroding polyanhydride nanoparticles (NPs) prepared from 1,6-bis(p-carboxyphenoxy)hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) administered...

The present study was designed to evaluate the adjuvant activity of polyanhydride microparticles prepared in the absence of additional stabilizers, excipients or immune modulators. Microparticles composed of varying ratios of either 1,6-bis(p-carboxyphenoxy)hexane (CPH) and sebacic acid or 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane and CPH were adde...

While vaccination has proven to be the most preventable method for eliminating infectious diseases over the past 200 years, infectious disease still remains a leading cause of death worldwide. Additionally, the rise in bioterrorism with biowarfare agents such as anthrax has demonstrated an urgent need for more effective vaccination strategies. In p...