- Bacillus and Francisella bacterial research
- Bacterial Genetics and Biotechnology
- Yersinia bacterium, plague, ectoparasites research
- Streptococcal Infections and Treatments
- Antimicrobial Resistance in Staphylococcus
- SARS-CoV-2 and COVID-19 Research
- Escherichia coli research studies
- Urinary Tract Infections Management
- Pneumonia and Respiratory Infections
- PARP inhibition in cancer therapy
- Antimicrobial Peptides and Activities
- Proteoglycans and glycosaminoglycans research
- Toxin Mechanisms and Immunotoxins
- Bacterial biofilms and quorum sensing
- Vaccine Coverage and Hesitancy
- Bacterial Identification and Susceptibility Testing
- HIV/AIDS oral health manifestations
- Viral Infections and Outbreaks Research
- Gut microbiota and health
- Microbial Inactivation Methods
- Herpesvirus Infections and Treatments
- Poxvirus research and outbreaks
- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Immunodeficiency and Autoimmune Disorders
Biomedical Advanced Research and Development Authority
2024
Uniformed Services University of the Health Sciences
2011-2018
National Institute of Allergy and Infectious Diseases
2008-2010
National Institutes of Health
2008-2010
University of Alabama at Birmingham
2000-2006
Staphylococcus aureus is a prominent human pathogen and leading cause of bacterial infection in hospitals the community. Community-associated methicillin-resistant S. (CA-MRSA) strains such as USA300 are highly virulent and, unlike hospital strains, often disease otherwise healthy individuals. The enhanced virulence CA-MRSA based part on increased ability to produce high levels secreted molecules that facilitate evasion innate immune response. Although progress has been made, factors...
Cytotoxic necrotizing factor 1 (CNF1) and hemolysin (HlyA1) are toxins produced by uropathogenic Escherichia coli (UPEC). We previously showed that these contribute to the inflammation tissue damage seen in a mouse model of ascending urinary tract infection. CNF1 constitutively activates small Rho GTPases deamidation conserved glutamine residue, HlyA1 forms pores eukaryotic cell membranes. In this study, we used cDNA microarrays bladder isolated from mice infected intraurethrally with...
Bacillus cereus G9241 was isolated from a welder with pulmonary anthrax-like illness. The organism contains two megaplasmids, pBCXO1 and pBC218. These plasmids are analogous to the anthracis Ames pXO1 pXO2 that encode anthrax toxins capsule, respectively. Here we evaluated virulence of B. as well contributions pBC218 virulence. avirulent in New Zealand rabbits after subcutaneous inoculation attenuated 100-fold compared published 50% lethal dose (LD(50)) values for aerosol inoculation. A/J...
Abstract Coronavirus disease 2019 (COVID-19) epidemiology and product landscapes have changed considerably since onset of the pandemic. Safe effective vaccines therapeutics are available, but continual emergence severe acute respiratory syndrome coronavirus 2 variants introduce limitations in our ability to prevent treat disease. Project NextGen is a collaboration between Biomedical Advanced Research Development Authority, part Administration for Strategic Preparedness Response, National...
ABSTRACT Synthesis of the Streptococcus pneumoniae type 3 capsule requires pathway glucose-6-phosphate (Glc-6-P) → Glc-1-P UDP-Glc UDP-glucuronic acid (UDP-GlcUA) (GlcUA-Glc) n . The dehydrogenase and synthase necessary for latter two steps, essential production, are encoded by genes ( cps3D cps3S , respectively) located in locus. phosphoglucomutase (PGM) uridylyltransferase activities first steps derived largely through actions cellular enzymes. Homologues these enzymes, cps3M cps3U locus,...
Regulation of chain length is essential to the proper functioning prokaryotic and eukaryotic polysaccharides. Modulation polymer size by substrate concentration an attractive but unexplored control mechanism that has been suggested for many The Streptococcus pneumoniae capsular polysaccharide virulence, regulation its critical survival in different host environments. Synthesis type 3 capsule [-4)-beta-d-Glc-(1-3)-beta-d-GlcUA-(1-] from UDP-glucose (UDP-Glc) UDP-glucuronic acid (UDP-GlcUA)...
Uropathogenic Escherichia coli (UPEC) is the leading cause of cystitis. Cytotoxic necrotizing factor 1 (CNF1) and hemolysin (Hly) are toxins made by approximately 50% UPEC isolates. CNF1 Hly contribute to robust inflammatory response in bladders mice challenged with strain CP9. We hypothesized that antibodies against and/or would reduce cystitis caused To test this theory, we immunized female C3H/HeOuJ subcutaneously a genetically derived toxoid or plus sublethal doses CNF1. collected serum...
Pneumonia caused by Staphylococcus aureus is a growing concern in the health care community. We hypothesized that characterization of early innate immune response to bacteria lungs would provide insight into mechanisms used host protect itself from infection. An adult mouse model pneumonia was utilized define events and assess changes airway proteome during first 6 h pneumonia. S. actively replicated mice inoculated intranasally under anesthesia cause significant morbidity mortality. By...
ABSTRACT Bacillus anthracis spores are the infectious form of organism for humans and animals. However, approved human vaccine in United States is derived from a vegetative culture filtrate toxigenic, nonencapsulated B. strain that primarily contains protective antigen (PA). Immunization mice with purified spore proteins formalin-inactivated (FIS) nonencapsulated, nontoxigenic confers protection against challenge when PA also administered. To investigate capacity particle to act as without...
Staphylococcus aureus is a major cause of hospital-acquired pneumonia and emerging as an important etiological agent community-acquired pneumonia. Little known about the specific host-pathogen interactions that occur when S. first enters airway. A shotgun proteomics approach was utilized to identify airway proteins associated with during 6 h infection. Host eluted from bacteria recovered airways mice 30 min or following intranasal inoculation under anesthesia were subjected liquid...
Bacillus cereus strain G9241 was isolated from a patient with pneumonia who had an anthrax-like illness. Like anthracis, the virulence of is dependent on two large plasmids. In those plasmids are pBCXO1 and pBC210. There multi-gene capsule locus each these plasmids, both capsules produced by in vitro mice. The hasACB operon responsible for production hyaluronic acid (HA) capsule. pBC210 encodes putative tetrasaccharide (TS) that assembles Wzy-dependent manner. We found transcribed as operons...
Bacillus cereus G9241 was isolated from a welder suffering an anthrax-like inhalation illness. B. encodes two megaplasmids, pBCXO1 and pBC210, which are analogous to the toxin- capsule-encoding virulence plasmids of anthracis. Protein modeling predicted that pBC210 LF homologue contained ADP-ribosyltransferase (ADPr) domain. This putative bacterial domain denoted CerADPr. Iterative showed CerADPr possessed several conserved features, including α-3 helix, turn-turn loop, "Gln-XXX-Glu" motif....
To ascertain whether epithelial cells of oral cavity origin may be infected with human immunodeficiency virus (HIV‐1), a study to determine susceptibility infection salivary gland cell lines (HSY and HSG) was undertaken. Because the potential for oral‐genital transmission, an endometrial line, HEC‐1, also studied. Epithelial monolayers were cell‐free HTLV IIIB or primary HIV‐1 isolate. Several evidence indicated that inoculation these led productive infection: 1) p24 antigen present in...
Summary AtxA is a critical transcriptional regulator of plasmid‐encoded virulence genes in Bacillus anthracis . cereus G9241, which caused an anthrax‐like infection, has two plasmids, pBCXO1 and pBC210, that each harbor toxin capsule locus. G9241 also produces orthologs AtxA: AtxA1, encoded on pBCXO1, AtxA2, pBC210. The amino acid sequence AtxA1 identical to from B. , while the sequences AtxA2 are 79% 91% similar one another. We found by qRT‐PCR function as positive regulators (AtxA1) operon...
The tetrasaccharide (2-O-methyl-4-(3-hydroxy-3-methylbutamido)-4,6-dideoxy-α-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-l-rhamnopyranose) from the major exosporium protein (BclA) of Bacillus anthracis has been proposed as a target for development diagnostics and immune therapy or prophylaxis. While immunodominant character anthrose residue previously elucidated, role stereochemical configuration downstream rhamnose is unknown. Because linkage this to GlcNAc...
Bacillus cereus G9241 caused a life-threatening anthrax-like lung infection in previously healthy human. This strain harbors two large virulence plasmids, pBCXO1 and pBC210, that are absent from typical B. isolates. The plasmid is nearly identical to pXO1 anthracis carries genes (pagA1, lef, cya) for anthrax toxin components (protective antigen [called PA1 G9241], lethal factor [LF], edema [EF], respectively). also has an intact hyaluronic acid capsule locus. pBC210 tetrasaccharide locus,...