F. Heath Damron

F. Heath Damron
West Virginia University | WVU · Department of Microbiology, Immunology and Cell Biology

Ph.D.

About

78
Publications
13,538
Reads
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1,142
Citations
Introduction
I study the biology of the respiratory pathogens: Pseudomonas aeruginosa, Burkholderia cenocepacia and Bordetella pertussis. My focus has been to understand the mechanisms of regulating the alternative sigma factor (AlgU/σ22/RpoE) which facilitates the ability of the organisms to adapt and survive. My current goal is to establish an independent research laboratory that will focus on discovering new targets for antibiotics as well as develop novel treatments with natural predatory bacteria
Additional affiliations
November 2014 - present
West Virginia University
Position
  • Professor (Assistant)
September 2013 - November 2014
University of Virginia
Position
  • Research Associate
Description
  • Investigating the virulence factors of Bordetella pertussis
July 2010 - July 2013
University of Virginia
Position
  • PostDoc Position
Description
  • Regulation of RpoE/AlgU and associated dependent virulence of Burkholderia cenocepacia and Pseudomonas aeruginosa

Publications

Publications (78)
Article
Full-text available
Pseudomonas aeruginosa is an opportunistic pathogen that can adapt to changing environments and can secrete an exopolysaccharide known as alginate as a protection response, resulting in a colony morphology and phenotype referred to as mucoid. However, how P. aeruginosa senses its environment and activates alginate overproduction is not fully unders...
Article
Full-text available
We describe the construction of mini-Tn7-based broad-host-range vectors encoding lux genes as bioluminescent reporters. These constructs can be mobilized into the desired host(s) by conjugation for chromosomal mini-Tn7-lux integration and are useful for localization of bacteria during infections or for characterizing regulation of promoters of inte...
Article
Pseudomonas aeruginosa, a Gram-negative bacterium, is a significant opportunistic pathogen associated with skin and soft tissue infections, nosocomial pneumonia and sepsis. In addition, it can chronically colonize the lungs of cystic fibrosis (CF) patients. Overproduction of the exopolysaccharide called alginate provides P. aeruginosa with a select...
Article
Full-text available
Bordetella pertussis is the causative agent of whooping cough (pertussis), a severe respiratory disease that can be fatal, particularly in infants. Despite high vaccine coverage, pertussis remains a problem because the currently used DTaP and Tdap vaccines do not completely prevent infection or transmission. It is well established that the alum adj...
Article
Full-text available
Emergence of variants of concern (VOC) during the COVID-19 pandemic has contributed to the decreased efficacy of therapeutic monoclonal antibody treatments for severe cases of SARS-CoV-2 infection. In addition, the cost of creating these therapeutic treatments is high, making their implementation in low- to middle-income countries devastated by the...
Article
Full-text available
Purpose The rapid spread of SARS-CoV-2, the virus that is responsible for causing COVID-19, has presented the medical community with another example of when convalescent plasma (CP) is still used today. The ability to standardize CP at the onset of a pandemic is unlikely to exist in a reliable and uniformly reproducible way. We hypothesized that CP...
Article
Full-text available
Background Lung airway epithelial cells are part of innate immunity and the frontline of defense against bacterial infections. During infection, airway epithelial cells secrete proinflammatory mediators that participate in the recruitment of immune cells. Virulence factors expressed by bacterial pathogens can alter epithelial cell gene expression a...
Preprint
SARS-CoV-2 infection results in wide-ranging disease manifestation from asymptomatic to potentially lethal. Infection poses an increased threat of severity to at-risk populations including those with hypertension, diabetes, and obesity. Type 2 Diabetes (T2DM), is characterized, in part, by insulin insensitivity and impaired glucose regulation. T2DM...
Article
Full-text available
SARS-CoV-2 is a viral respiratory pathogen responsible for the current global pandemic and the disease that causes COVID-19. All current WHO approved COVID-19 vaccines are administered through the muscular route. We have developed a prototype two-dose vaccine (BReC-CoV-2) by combining the Receptor Binding Domain (RBD) antigen, via conjugation to Di...
Article
Full-text available
Over two decades ago acellular pertussis vaccines (aP) replaced whole cell pertussis vaccines (wP) in several countries. Since then, a resurgence in pertussis has been observed, which is hypothesized to be linked, in part, to waning immunity. To better understand why waning immunity occurs, we developed a long-term outbred CD1 mouse model to conduc...
Article
Full-text available
SARS-CoV-2 variants of concern (VoC) are impacting responses to the COVID-19 pandemic. Here, we utilized passive immunization using human convalescent plasma (HCP) obtained from a critically ill COVID-19 patient in the early pandemic to study the efficacy of polyclonal antibodies generated to ancestral SARS-CoV-2 against the Alpha, Beta, and Delta...
Preprint
The COVID-19 pandemic has been fueled by novel variants of concern (VOC) that have increased transmissibility, receptor binding affinity, and other properties that enhance disease. The goal of this study is to characterize unique pathogenesis of the Delta VOC strain in the K18-hACE2-mouse challenge model. Challenge studies suggested that the lethal...
Preprint
Full-text available
Over two decades ago acellular pertussis vaccines (aP) replaced whole cell pertussis vaccines (wP) in several countries. Since then, a resurgence in pertussis has been observed, which is hypothesized to be linked to waning immunity. To better understand why waning immunity occurs, we developed a long-term outbred CD1 mouse model to conduct the long...
Article
Full-text available
Pertussis is a respiratory disease caused by the Gram-negative pathogen, Bordetella pertussis ( Bp ). The transition from a whole cell pertussis vaccine (wP; DTP) to an acellular pertussis vaccine (aP; DTaP; Tdap) correlates with an increase in pertussis cases, despite widespread vaccine implementation and coverage, and it is now appreciated that t...
Preprint
Full-text available
The SARS-CoV-2 pandemic has affected all types of global communities. Differences in urban and rural environments have led to varying levels of transmission within these subsets of the population. To fully understand the prevalence and impact of SARS-CoV-2 it is critical to survey both types of community. This study establishes the prevalence of SA...
Preprint
Full-text available
Pertussis is a respiratory disease caused by the Gram-negative pathogen, Bordetella pertussis ( Bp ). The transition from a whole cell pertussis vaccine (wP; DTP) to an acellular pertussis vaccine (aP; DTaP; Tdap) correlates with an increase in pertussis cases, despite widespread vaccine implementation and coverage, and it is now appreciated that t...
Article
Full-text available
Bordetella pertussis ( Bp ) is a highly contagious bacterium that is the causative agent of whooping cough (pertussis). Currently, acellular pertussis vaccines (aP; DTaP; Tdap) are used to prevent pertussis disease. However, it is clear that the aP vaccine efficacy quickly wanes, resulting in the re-emergence of pertussis. Furthermore, recent work...
Preprint
Full-text available
SARS-CoV-2 variants of concern (VoCs) are impacting responses to the COVID-19 pandemic. Here we present a comparison of the SARS-CoV-2 USA-WA1/2020 (WA-1) strain with B.1.1.7 and B.1.351 VoCs and identify significant differences in viral propagation in vitro and pathogenicity in vivo using K18-hACE2 transgenic mice. Passive immunization with plasma...
Article
Full-text available
The SARS-CoV-2 pandemic is impacting the global population. This study was designed to assess the interplay of antibodies with the cytokine response in SARS-CoV-2 patients. We demonstrate that significant levels of anti-SARS-CoV-2 antibody to receptor binding domain (RBD), nucleocapsid, and spike S1 subunit of SARS-CoV-2 develop over the first 10 t...
Article
Full-text available
Bordetella pertussis colonizes the respiratory mucosa of humans, inducing an immune response seeded in the respiratory tract. An individual, once convalescent, exhibits long-term immunity to the pathogen. Current acellular pertussis (aP) vaccines do not induce the long-term immune response observed after natural infection in humans. In this study,...
Article
Full-text available
Pseudomonas aeruginosa is a Gram-negative pathogen that causes severe pulmonary infections associated with high morbidity and mortality in immunocompromised patients. The development of a vaccine against P. aeruginosa could help prevent infections caused by this highly antibiotic-resistant microorganism. We propose that identifying the vaccine-indu...
Article
Full-text available
Whole cell vaccines are frequently the first generation of vaccines tested for pathogens and can inform the design of subsequent acellular or subunit vaccines. For respiratory pathogens, administration of vaccines at the mucosal surface can facilitate the generation of a localized mucosal immune response. Here, we examined the innate and vaccine-in...
Preprint
Full-text available
The SARS-CoV-2 pandemic is continuing to impact the global population. This study was designed to assess the interplay of antibodies with the systemic cytokine response in SARS-CoV-2 patients. We demonstrate that significant anti-SARS-CoV-2 antibody production to Receptor Binding Domain (RBD), Nucleocapsid (N), and Spike S1 subunit (S1) of SARS-CoV...
Article
Full-text available
Despite high vaccine coverage in many parts of the world, pertussis is resurging in a number of areas in which acellular vaccines are the primary vaccine administered to infants and young children. This is attributed in part to the suboptimal and short-lived immunity elicited by acellular pertussis vaccines and to their inability to prevent nasal c...
Article
Full-text available
An acellular pertussis vaccine is used to protect against whooping cough, caused by the bacterial pathogen Bordetella pertussis; however, there is a growing number of pertussis cases despite vaccination. Here Dylan Boehm and colleagues combine the acellular vaccine with a pro-inflammatory adjuvant to maximise the mucosal immune response when admini...
Preprint
Full-text available
Bordetella pertussis (B. pertussis) is the causative agent of pertussis (whooping cough). Since the 1990s, pertussis has re-emerged in the United States despite an estimated 95% vaccine coverage. Our goal was to characterize neutrophil responses and gene expression profiles of murine lungs in the context of vaccination and B. pertussis challenge. W...
Article
Full-text available
Bordetella pertussis is the causative agent of whooping cough, a serious respiratory illness affecting children and adults, associated with prolonged cough and potential mortality. Whooping cough has reemerged in recent years, emphasizing a need for increased knowledge of basic mechanisms of B. pertussis growth and pathogenicity. While previous stu...
Article
Full-text available
This report provides evidence for motility and expression of flagella by B. pertussis , a bacterium that has been reported as nonmotile since it was first isolated and studied. As with B. bronchiseptica , B. pertussis cells can express and assemble a flagellum-like structure on their surface, which in other organisms has been implicated in several...
Article
Full-text available
In vitro growth conditions for bacteria do not fully recapitulate the host environment. RNA sequencing transcriptome analysis allows for the characterization of the infection gene expression profiles of pathogens in complex environments. Isolation of the pathogen from infected tissues is critical because of the large amounts of host RNA present in...
Article
Full-text available
Hematopoietic stem and progenitor cell (HSPC) compartments are altered to direct immune responses to infection. Their roles during immunization are not well-described. To elucidate mechanisms for waning immunity following immunization with acellular vaccines (ACVs) against Bordetella pertussis (Bp), we tested the hypothesis that immunization with B...
Data
Compositions of vaccines of this study.
Data
Summary of RNAseq performed in this study.
Data
WCV induces alterations in spleen size and B and T cell population composition. (A). Spleen sizes from CD-1 mice (n = 4/group for each time point) immunized with phosphate buffered saline (PBS), Bp acellular vaccine (ACV), or Bp whole cell vaccine (WCV) are shown in representative images for the indicated time points across the immunization and inf...
Data
Enlargement of the post-immunization transcriptional landscape of HSPCs B cell clonal repertoires. Pairwise overlap circos plots of HSPC B cell clonal repertoires (n=6mice/group) prepared using MiXCR software and shown in Figure 5A were enlarged for viewing individual clones. Count, frequency and diversity panels correspond to the read count, frequ...
Data
Vaccine content determines gene set enrichment of HSPCs. RNAseq was performed on HSPCs isolated from CD-1 mice on days 1 and 3 post immunization with PBS, ACV, or WCV and on days 1 and 3 post subsequent infection with Bp. (A) Venn diagram was prepared for significant differentially expressed genes in HSPCs of ACV- and WCV-immunized mice when compar...
Data
Enlargement of controls for the transcriptional landscape of HSPCs B cell clonal repertoires. Pairwise overlap circos plots of HSPC B cell clonal repertoires (n = 6mice/group) prepared using MiXCR software and shown in Figure 5A were enlarged for viewing individual clones. Count, frequency and diversity panels correspond to the read count, frequenc...
Data
Flow cytometry antibodies used in this study.
Data
Enlargement of the post-infection transcriptional landscape of HSPCs B cell clonal repertoires. Pairwise overlap circos plots of HSPC B cell clonal repertoires (n = 6mice/group) prepared using MiXCR software and shown in Figure 5A were enlarged for viewing individual clones. Count, frequency and diversity panels correspond to the read count, freque...
Article
Full-text available
Bordetella pertussis ( Bp ) is the primary causative agent of pertussis (whooping cough), which is a respiratory infection that leads to a violent cough and can be fatal in infants. There is a need to develop more effective vaccines because of the resurgence of cases of pertussis in the US since the switch from the whole cell pertussis vaccines (wP...
Article
Full-text available
Pseudomonas aeruginosa employs numerous, complex regulatory elements to control expression of its many virulence systems. The P. aeruginosa AlgZR two-component regulatory system controls the expression of several crucial virulence phenotypes. We recently determined, through transcriptomic profiling of a PAO1 ΔalgR mutant strain compared to wild-typ...
Preprint
Full-text available
Bordetella pertussis is an obligate human respiratory pathogen that causes the disease whooping cough. A whole cell vaccine (DTP) was developed in the 1940s and was subsequently replaced in the 1990s with a protein-based subunit acellular vaccine (DTaP; tdap). Today, we are observing a resurgence of whooping cough due to evolution of the pathogen a...
Article
Full-text available
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that requires iron for virulence. Iron homeostasis is maintained in part by the PrrF1 and PrrF2 small RNAs, which block the expression of iron-containing proteins in iron-depleted conditions. The PrrF sRNAs also promote the production of the Pseudomonas quinolone signal, a quorum sens...
Poster
Pseudomonas aeruginosa is one of the major opportunistic pathogens responsible for hospital-acquired infections associated with high morbidity and mortality. The ability to adapt to different environments and multi-drug resistance make this bacterium a major health concern. Vaccination against P. aeruginosa could provide a solution against these in...
Poster
Bordetella pertussis is the causative agent of pertussis (whooping cough), a respiratory infection leading to a violent cough, which can be fatal in infants. Acellular pertussis vaccines (ACV) replaced whole cell vaccines (WCV) in the US immunization schedule in the early 1990s, and for multiple reasons, pertussis is re-emerging despite 95% vaccine...
Article
Full-text available
Determining bacterial gene expression during infection is fundamental to understand pathogenesis. In this study, we used dual RNA-seq to simultaneously measure P. aeruginosa and the murine host’s gene expression and response to respiratory infection. Bacterial genes encoding products involved in metabolism and virulence were differentially expresse...
Article
Full-text available
Bordetella pertussis is a human pathogen that can infect the respiratory tract and cause the disease known as whooping cough. B. pertussis uses pertussis toxin (PT) and adenylate cyclase toxin (ACT) to kill and modulate host cells to allow the pathogen to survive and persist. B. pertussis encodes many uncharacterized transcription factors and very...
Article
Full-text available
Since their discovery, fluorescent proteins have been widely used to study protein function, localization or interaction, promoter activity and regulation, drug discovery or for non-invasive imaging. They have been extensively modified to improve brightness, stability, and oligomerization state. However, only a few studies have focused on understan...
Data
Plasmids used as template to amplify fluorescent proteins. (DOCX)
Data
Oligonucleotides used in this study. (DOCX)
Article
Full-text available
Bacteria use alternative sigma factors (σs) to regulate condition-specific gene expression for survival and Shewanella harbors multiple ECF (extracytoplasmic function) σ genes and cognate anti-sigma factor genes. Here we comparatively analyzed two of the rpoE-like operons in the strain MR-1: rpoE-rseA-rseB-rseC and rpoE2-chrR. RpoE was important fo...
Article
Full-text available
Background Pseudomonas aeruginosa is an environmentally ubiquitous Gram-negative bacterium and important opportunistic human pathogen, causing severe chronic respiratory infections in patients with underlying conditions such as cystic fibrosis (CF) or bronchiectasis. In order to identify mechanisms responsible for adaptation during bronchiectasis i...
Article
Full-text available
Pseudomonas aeruginosa is a highly versatile opportunistic pathogen capable of colonizing multiple ecological niches. This bacterium is responsible for a wide range of both acute and chronic infections in a variety of hosts. The success of this microorganism relies on its ability to adapt to environmental changes and re-program its regulatory and m...
Article
Full-text available
Alginate overproduction in P. aeruginosa, also referred to as mucoidy, is a poor prognostic marker for patients with cystic fibrosis (CF). We previously reported the construction of a unique mucoid strain which overexpresses a small envelope protein MucE leading to activation of the protease AlgW. AlgW then degrades the anti-sigma factor MucA thus...
Data
Full-text available