Doi Laboratory

Dr. Yohei Doi has conducted research on antimicrobial-resistant bacteria over the last 17 years, deciphering the molecular epidemiology and resistance mechanisms of Acinetobocter boumannii has been a major theme of his work with ample experience in both leading and collaborating on multicenter observational clinical studies addressing antimicrobial resistance.

Contribution to Science

• Clinical and laboratory studies addressing emerging resistance in Acinetobacter baumannii Acinetabacter baumannii has emerged as one of the most formidable drug-resistant pathogens in hospitals in the US and worldwide. Conducted clinical, laboratory and translational studies to address clinically relevant questions. Including discovery of novel aminoglycoside resistance mechanisms in this pathogen, molecular epidemiology of carbapenem-resistant A baumannii in the U.S., studies to improve infection control elucidation of virulence of various Acinetobacter spp., and identification of colistin resistance mechanisms and their clinical implications.

• Characterization of novel beta-lactamases with unique substrate profiles I have conducted a series of studies to characterize, both genetically and kinetically, beta-lactamases that possess unique substrate profiles, including from A baumannii. These studies have led to improved understanding of key residues that define the kinetic activities and inhibition of various beta-lactamase, especially of those in the molecular class C

• Clinical studies an antimicrobial-resistant gram-negative infections Antimicrobial resistance can severely limit treatment options for infections. Dr. Doi leads a series of clinical studies in an effort to better identify and t reat resistant gram-negative infections. We have identified risk factors and clinical outcome of infections caused by ESBLproducing Enterabacteriaceae and KPC-producing Enterobacteriaceae

• Fosfomycin resistance in E. coli and clinical implications Conduct ing a series of studies to elucidate the clinical utility of fosfomycin, a “re-discovered antibiotic” in the era of antimicrobial resistance, characterize emerging mechanisms of fosfomycin resistance in E. coli and vancomycin-resistant enterococci, examine the activity of foscarnet in reversing fosfomycin resistance, and describing the genetic basis for spontaneous fosfomycin resistance of E. coli, a phenomenon encountered in clinical microbiology laboratories (ref 8) The long-term goal of this ongoing effort is to identify methods to reverse fosfomycin resistance which is spreading in Enterobacteriaceae

• 165 ribosomal RNA methyltransferase as an emerging mechanism of aminaglycoside resistance Aminoglycoside is one of the key classes of antimicrobial agents against gram-negat ive bacteria along with beta-lactams and fluoroquinolones. The lab team has discovered a number of novel 16S ribosomal RNA methyltransferases.The series of work has opened up a new field of investigation for many researchers worldwide.