Dong H. Kwon
Professor of Biology
Post-Doc, Baylor College of Medicine Ph.D., Georgia State University
Dong.kwon@liu.edu
Description
My research interests have centered in pharmaceutical biotechnology focusing on the molecular details of drug susceptibility/resistance mechanisms, finding new drug targets (or a new drug), and novel strategies to treat drug resistant bacterial pathogens.
My study was on a human pathogen, Helicobacter pylori (H. pylori), which is a Gram-negative bacterium infecting more than 50% of the human population. H. pylori infection is etiologically associated with peptic ulcer disease, gastric lymphoma, and gastric cancer. Cure of the infection cures peptic ulcer disease and if done early in the course of the infection will prevent development of the H. pylori-related diseases including gastric cancer. While H. pylori is susceptible to most common antibiotics in vitro, clinically cure of the infection has proven difficult. Current H. pylori eradication therapies consist of combinations of two or more antibiotics including amoxicillin, clarithromycin, metronidazole, or tetracycline and antisecretory drugs. Overall, the cure rate in clinical practice has been in the range of 60 to 80%. Failure of treatment is most frequently due to the presence of H. pylori acquired resistance to amoxicillin, clarithromycin, metronidazole, and/or tetracycline. My work was devoted to understanding the molecular details of resistance mechanisms to amoxicillin, clarithromycin, metronidazole, and tetracycline. The molecular bases of resistance to these antibiotics were chromosomal mutations on the antibiotic-target genes, (e.g., a gene encoding penicillin-binding protein [pbp-1A] for amoxicillin, genes encoding 23S rRNA for clarithromycin, genes encoding 16S rRNA for tetracycline, and a gene encoding metronidazole nitroreductase [rdxA] for metronidazole).
My recent studies moved on Gram-negative pathogens of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa, which are the most problematic multidrug resistant (MDR) human pathogens. The widespread emergence of these MDR pathogens has compromised the utility of existing treatment options in healthcare-associated infections and nosocomial outbreaks, and infections caused by the MDR pathogens gravely impact on mortality and morbidity as well as prolonging hospital stays and costs. Untreatable MDR Gram-negative pathogens have increasingly been reported worldwide; deaths due to the MDR Gram-negative infections have also been reported.
My research has used non-antibiotic and non-toxic natural compounds that restore susceptibility of existing antibiotics against the MDR pathogens. Preliminary results suggest that the natural compounds are associated with disrupting intracellular redox homeostasis and restoring the susceptibility of antibiotics regardless of MDR. Molecular details of this finding are currently deciphering.
Specialties
Molecular Genetics of Microorganisms; Molecular Mechanism of Antimicrobial Susceptibility/Resistance; Biochemistry
Publications
Publications
Co-author, “R-Plasmids in Staphylococcus aureus,” published in J Microbiol
Co-author, “Studies on antibiotics resistance gene in Staphylococcus aureus plasmid: cloning of chloramphenicol resistance determinant,” published in J Microbiol
Co-author, “Cloning of ori region of R-plasmid pSBK203 and construction of new shuttle-vector for E. coli and B. subtilis using cloned fragments,” published in J Microbiol
Co-author, “Nucleotide Sequence and Inducibility Analysis of Chloramphenicol Acetyltransferase Gene from Staphylococcus aureus R-plasmid pSBK203,” published in J Microbiol
Co-author, “Nucleotide sequence and properties of Macrolide-Lincosamide-Streptogramin B resistance gene from Staphylococcus aureus DH1,” published in J Microbiol
Co-author, “Cloning and base sequence determination of replication initiation gene (rep) isolated from Staphylococcus aureus DH1 R-plasmid pSBK203,” published in J Microbiol
Co-author, “Structure and regulation of the carAB operon in Pseudomonas aeruginosa and Pseudomonas stutzeri: no untranslated region exists,” published in J Bacteriol
Co-author, “Identification of greA encoding a transcriptional elongation factor as a member of the carA-orf-carB-greA operon in Pseudomonas aeruginosa PAO1,” published in J Bacteriol
Co-author, “Demonstration of unexpected antibiotic resistance of genotypically identical Helicobacter pylori isolates,” published in Clin Infect Dis
Co-author, “The effect of galE gene inactivation on lipopolysaccharide profile of Helicobacter pylori,” published in Curr Microbiol
Co-author, “REP-PCR fragments as biomarkers for differentiating gastroduodenal disease-specific Helicobacter pylori strains,” published in Dig Dis Sci
Co-author, “Isolation and characterization of tetracycline-resistant clinical isolates of Helicobacter pylori,” published in Antimicrob Agents Chemother
Co-author, “Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter pylori isolates,” published in J Antimicrob Chemother
Co-author, “A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori,” published in Proc Natl Acad Sci USA
Co-author, “Quantitative RT-PCR analysis of multiple genes encoding putative metronidazole nitroreductases from Helicobacter pylori,” published in Int J Antimicrob Agents
Co-author, “Regional differences in metronidazole resistance and increasing clarithromycin resistance among Helicobacter pylori isolates from Japan,” published in Antimicrob Agents Chemother
Co-author, “Analysis of rdxA and involvement of additional genes encoding NAD(P)H flavin oxidoreductase (FrxA) and ferredoxin-like protein (FdxB) in metronidazole resistance of Helicobacter pylori,” published in Antimicrob Agents Chemother
Co-author, “Metronidazole containing quadruple therapy for infection with metronidazole resistant Helicobacter pylori: a prospective study,” published in Aliment Pharmacol Ther
Co-author, “Frame-shift mutations in NAD(P)H flavin oxidoreductase encoding gene (frxA) from metronidazole resistant Helicobacter pylori ATCC43504 and its involvement in metronidazole resistance,” published in FEMS Microbiol Letter
Co-author, “Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea,” published in J Antimicrob Chemother
Co-author, Stable amoxicillin resistance in Helicobacter pylori. Helicobacter. 2001;6:79
Co-author, “Nitrofurantoin quadruple therapy for Helicobacter pylori infection: effect of metronidazole resistance,” published in Aliment Pharmacol Ther
Co-author, “Furazolidone- and nitrofurantoin-resistant Helicobacter pylori: prevalence and role of genes involved in metronidazole resistance,” published in Antimicrob Agents Chemother
Co-author, “DNA sequence analysis of rdxA and frxA from 12 pairs of metronidazole-sensitive and -resistant clinical Helicobacter pylori isolates,” published in Antimicrob Agents Chemother
Co-author, “Mixed-infection of antibiotic susceptible and resistant Helicobacter pylori isolates in a single patient and underestimation of antimicrobial susceptibility testing,” published in Helicobacter
Co-author, “Studies of High-Level b-Lactam Antibiotic Resistance Associated with Acquired Multidrug Resistance in Helicobacter pylori,” published in Antimicrob Agents Chemother
Co-author, “The arginine regulatory protein mediates repression by arginine of the operons encoding glutamate synthase and anabolic glutamate dehydrogenase in Pseudomonas aeruginosa,” published in J Bacteriol
Co-author, “Tetracycline-resistant clinical Helicobacter pylori isolates with and without mutations in 16S rRNA-encoding genes,” published in Antimicrob Agents Chemother
Co-author, “In vitro induction of resistance to metronidazole, and analysis of mutations in rdxA and frxA genes from Helicobacter pylori isolates,” published in J Infect Chemother
Co-author, “Isogenic Variation of Helicobacter pylori Strain Resulting in Heteroresistant Antibacterial Phenotypes in a Single Host In Vivo,” published in Helicobacter
Co-author, “Polyamines induce resistance to cationic peptide, aminoglycoside, and quinolone antibiotics in Pseudomonas aeruginosa PAO1,” published in Antimicrob Agents Chemother
Co-author, “Polyamines increase antibiotic susceptibility in Pseudomonas aeruginosa,” published in Antimicrob Agents Chemother
Co-author, “Polyamine effects on antibiotic susceptibility in bacteria,” published in Antimicrob Agents Chemother
Co-author, “Transcriptome Analysis of Agmatine and Putrescine Catabolism in Pseudomonas aeruginosa PAO1,” published in J Bacteriol
Co-author, “Fur-independent induction of Helicobacter pylori flavodoxin-encoding gene (fldA) under iron starvation,” published in Helicobacter
Co-author, “A Single Amino Acid Substitution in PmrB Is Associated with Polymyxin B Resistance in Clinical Isolate of Pseudomonas aeruginosa,” published in FEMS Microbial Letters
Co-author, “Alterations in Two-Component Regulatory Systems of phoPQ and pmrAB Are Associated with Polymyxin B Resistance in Clinical Isolates of Pseudomonas aeruginosa,” published in Antimicrobial Agents and Chemotherapy
Co-author, “Co-Existence of Multidrug-Resistant and -Susceptible Strains of Pseudomonas aeruginosa from a Single Clinical Isolate,” published in Current Microbiology
Co-author, “Surface Modification of Poly(amidoamine) (PAMAM) Dendrimer as Antimicrobial Agents,” published in Tetrahedron Letters
Co-author, “Differential Role of Two-Component Regulatory Systems (phoPQ and pmrAB) in Polymyxin B Susceptibility of Pseudomonas aeruginosa,” published in Advances in Microbiology
Co-author, “Carbapenem-associated multidrug-resistant Acinetobacter baumannii are sensitized by aztreonam in combination with polyamines,” published in International Journal of Antimicrobial Agents
Co-author, “Homeostasis of Glutathione Is Associated with Polyamine-Mediated beta-Lactam Susceptibility in Acinetobacter baumannii ATCC 19606,” published in Antimicrobial Agents and Chemotherapy
Co-author, “Promoter Deletions of Klebsiella pneumoniae Carbapenemase (KPC)-Encoding Genes (blaKPC-2) and Efflux Pump (AcrAB) on b-Lactam Susceptibility in KPC-Producing Enterobacteriaceae,” published in FEMS Microbiology Letters
Co-author, “Complete Genome Sequences of Helicobacter pylori Clarithromycin-Resistant Strains,” published in Genome Announcement
Co-author, “Discovery of novel mutations for clarithromycin resistance in Helicobacter pylori by using next-generation sequencing,” published in J Antimicrob Chemotherapy
Co-author, “Dissemination and Genetic Structure of Carbapenemase Encoding Genes (blaOXA-23 and blaOXA-24) in Acinetobacter baumannii from Southern Texas,” published in Advances in Microbiology
Co-author, “Retention of Glutathione-Specific Acidity and Disruption of Intracellular Glutathione-Redox Homeostasis are Associated with Antibacterial Activity in Pseudomonas aeruginosa,” published in Int J Curr Microbiol App Sci
Co-author, “Complete Genome Sequence of a Metronidazole-Resistant Helicobacter pylori Strain,” published in Genome Announcement
Co-author, “Search for novel candidate mutations for metronidazole resistance in Helicobacter pylori using next-generation sequencing,” published in Antimicrobial Agents and Chemotherapy
Co-author, “Surface modification and antimicrobial properties of cellulose nanocrystals,” published in J Appl Polym
Co-author, “Antibacterial activity of epigallocatechin-3-gallate (EGCG) and its synergism with β-lactam antibiotics sensitizing carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii,” published in Phytomedicine
Co-author, “Antibacterial Activity of Exogenous Glutathione and Its Synergism on Antibiotics Sensitize Carbapenem-Associated Multidrug Resistant Clinical Isolates of Acinetobacter baumannii,” published in Inter J Med Microb
Co-author, “An Efflux Pump (MexAB-OprM) of Pseudomonas aeruginosa Is Associated With Antibacterial Activity of Epigallocatechin-3gallate (EGCG),” published in Phytomedicine
Honors/Awards
Young Scientist Award in Xth International Workshop on Gastroduodenal Pathology and Helicobacter pylori
The Best Paper in Drug Resistance in Helicobacter pylori in Third Annual Winter H. pylori Workshop
First Prize awarded at the The 5th Annual meeting of the Japanese Society for Helicobacter Research
NIH Research grant
Patent, U.S. Patent No. 11/420,671 "Use of Polyamines with Antibiotics".
Member, American Society for Microbiology
Member, American Gastroenterology Association
