A5005992045- Antibiotic Resistance in Bacteria
- Bacterial biofilms and quorum sensing
- Microbial Natural Products and Biosynthesis
- Antimicrobial Peptides and Activities
- Plant-Microbe Interactions and Immunity
- Biochemical and Structural Characterization
- Marine Sponges and Natural Products
- Bacteriophages and microbial interactions
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical Synthesis and Analysis
- Cancer therapeutics and mechanisms
- Quinazolinone synthesis and applications
- Antimicrobial agents and applications
- vaccines and immunoinformatics approaches
- Synthetic Organic Chemistry Methods
- Plant Pathogens and Fungal Diseases
- Escherichia coli research studies
- bioluminescence and chemiluminescence research
- Biochemical and Molecular Research
- Legionella and Acanthamoeba research
- Computational Drug Discovery Methods
- Enzyme Production and Characterization
- Aquaculture disease management and microbiota
- Antimicrobial Resistance in Staphylococcus
- X-ray Diffraction in Crystallography
University of Central Florida
2023-2025
University of Florida
2025
University of Georgia
2025
Franklin College
2025
Integra (United States)
2024
The University of Texas at Austin
2020-2023
University of South Florida
2013-2018
Institute of Molecular and Cell Biology
2015
A series of N(2),N(4)-disubstituted quinazoline-2,4-diamines has been synthesized and tested against multidrug resistant Staphylococcus aureus. structure-activity structure-property relationship study was conducted to identify new hit compounds. This led the identification with minimum inhibitory concentrations (MICs) in low micromolar range addition favorable physicochemical properties. Testing biological activity revealed limited potential for resistance these agents, toxicity, highly...
Mixture based synthetic combinatorial libraries offer a tremendous enhancement for the rate of drug discovery, allowing activity millions compounds to be assessed through testing exponentially fewer samples. In this study, we used scaffold-ranking library screen 37 different antibacterial against ESKAPE pathogens. Each contained between 10000 and 750000 structural analogues total >6 million compounds. From this, identified bis-cyclic guanidine that displayed strong activity. A positional...
A new rearranged spongian diterpene, darwinolide, has been isolated from the Antarctic Dendroceratid sponge Dendrilla membranosa. Characterized on basis of spectroscopic and crystallographic analysis, central seven-membered ring is hypothesized to originate a ring-expansion precursor. Darwinolide displays 4-fold selectivity against biofilm phase methicillin-resistant Staphylococcus aureus compared planktonic may provide scaffold for development therapeutics this difficult treat infection.
Significance The capsule of Klebsiella pneumoniae is composed extracellular polysaccharides that inhibit the activity host defense peptides and polymyxins. We generated an active antimicrobial peptide from a previously inactive parental characterized interactions these with K. its capsule. Compared parent peptide, we found our retained strong binding to but lost structural integrity. These induced aggregation disruption, undescribed mechanism for promoting toward . This finding may allow...
Hypervirulent Klebsiella pneumoniae is known for its increased extracellular polysaccharide production. Biofilm matrices of hypervirulent K. have abundance and are uniquely susceptible to disruption by peptide bactenecin 7 (bac7 (1–35)). Here, using confocal microscopy, we show that polysaccharides within the biofilm matrix collapse following bac7 (1–35) treatment. This led release cells from biofilm, which were then killed peptide. Characterization truncated analogs revealed their...
The recent increase in extensively drug-resistant bacterial pathogens and the associated of morbidity mortality demonstrate immediate need for new antibiotic backbones with novel mechanisms action. Here, we report development PepSAVI-MS pipeline bioactive peptide discovery. This highly versatile platform employs mass spectrometry statistics to identify targets from complex biological samples. We validate use this through successful identification known peptides a botanical species, Viola...
We have previously reported the use of combinatorial chemistry to identify broad-spectrum antibacterial agents. Herein, we extend our analysis this technology toward discovery anti-resistance molecules, focusing on efflux pump inhibitors. Using high-throughput screening against multi-drug resistant Pseudomonas aeruginosa, identified a polyamine scaffold that demonstrated strong inhibition without possessing effects. determined these molecules were most effective with an amine functionality...
Klebsiella pneumoniae produces a thick capsule layer composed of extracellular polysaccharides protecting the bacterial cells from clearance by innate host immunity during infection. Here we characterize interactions structurally diverse set defense peptides with K. polysaccharides. Remarkably, found that all were active against strains, including hypermucoviscous strains extensive production, and aggregated extracted capsule. Interestingly, polyproline peptide bac7 (1-35), was most potent...
Klebsiella pneumoniae infections have become a growing threat for human health. The lack of understanding the relationship between antibiotic resistance, mucoviscosity, and biofilm formation impedes our abilities to effectively predict K. infection outcomes. Multidrug-Resistant Organism Repository Surveillance Network offers unique opportunity into genetic phenotypic variabilities in isolates. To this end, we compared profiles these isolates with formation, percent growth rates. There was...
Bacterial biofilms are surface-attached communities consisting of non-replicating persister cells encased within an extracellular matrix biomolecules. Unlike bacteria that have acquired resistance to antibiotics, enable demonstrate innate tolerance toward all classes conventional antibiotic therapies. It is estimated 50-80% bacterial infections biofilm associated, which considered the underlying cause chronic and recurring infections. Herein, we report a modular three-step synthetic route...
Carbapenem resistant Klebsiella pneumoniae extreme drug resistance has warranted the use of colistin as a last-resort antibiotic but these isolates are now displaying increasing rates resistance. This is in large part due to modifications made lipid A by PhoPQ two component system. Host defense peptides (HDPs) like that they both positively charged and display amphipathic character, however not impacted extent colistin. To understand how HDPs can penetrate membranes we performed deep...
There is an acute need for new and effective agents to treat infectious diseases. We conducted a screening program assess the potential of mangrove-derived endophytic fungi as source antibiotics. Fungi cultured in presence absence small molecule epigenetic modulators were screened against Mycobacterium tuberculosis ESKAPE panel bacterial pathogens, well two eukaryotic infective agents, Leishmania donovani Naegleria fowleri. By comparison bioactivity data among treatments targets, trends...
We previously reported a series of N2,N4-disubstituted quinazoline-2,4-diamines as dihydrofolate reductase inhibitors with potent in vitro and vivo antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. In this work, we extended our previous study to the Gram-negative pathogen Acinetobacter baumannii determined that optimized are strongly multidrug-resistant A. strains when 6-position is replaced halide or an alkyl substituent. Such agents display...
Klebsiella pneumoniae biofilm formation is associated with chronic and relapsing infections. Scanning electron microscopy (SEM) a powerful tool for characterizing structure studying their formation. Reliable visualization of requires careful sample preservation, otherwise there may be loss non-covalent interactions that are susceptible to damage during the dehydration washing preparation steps. However, no standard procedure has been adopted in literature fix K. scanning studies. This lack...
Abstract Cyclic lipopeptides derived from the fusaricidin/LI‐F family of naturally occurring antibiotics represent particularly attractive candidates for development new antibacterial agents. In comparison with natural products, these derivatives may offer better stability under physiologically relevant conditions and lower nonspecific toxicity, while preserving their activity. this study we assessed ability cyclic lipodepsipeptide 1 its analogues—amide 2 , N ‐methylamide 3 linear peptide 4...
The DedA superfamily is a highly conserved family of membrane proteins. Deletion
The rise in antimicrobial resistance and the decline new antibiotics has created a great need for novel approaches to treat drug resistant bacterial infections. Increasing burden of resistance, virulence factors allow survival within host, where they can evade host killing therapy their intracellular niches. Repurposing directed therapeutics potential adjuvants more effective by antimicrobials. To this end, phosphoinositide 3-kinase inhibitors are FDA approved cancer therapy, but also have...
<title>Abstract</title> <italic>Klebsiella pneumoniae</italic> infections have become a growing threat for human health. The lack of understanding the relationship between antibiotic resistance, mucoviscosity, and biofilm formation in clinical isolates impedes our abilities to effectively predict <italic>K. infection outcomes. These traits are also associated with fitness natural populations more specifically within host. Multidrug-Resistant Organism Repository Surveillance Network offers...
Chemically diverse and largely under-studied, mangrove endophytic fungi represent a valuable source of natural products for drug discovery screening program. While classical lab fermentation techniques may not reveal the full chemical potential these organisms, epigenetic modification can encourage otherwise down-regulated biosynthetic capabilities to be realized. As part two NIH funded projects, were grown under control epigenetically modified conditions, extracted, submitted biological...
The harsh and competitive environment in which marine microbes live instigate the production of chemical defenses. When cultured, these environmental pressures are not present, leading to down-regulation some biosynthetic pathways. Artificial stressors often applied activate an enhanced metabolic response laboratory setting. For example, upon epigenetic modification, endophytic fungi from Floridian mangroves have been found produce secondary metabolites observed untreated cultures, increase...