Anastasia Koutsolioutsou

Demple Laboratory
Harvard School of Public Health

 

My research interests lie at the interplay between oxidative stress and antibiotic resistance in bacteria. Both oxidative stress and antibiotic resistance are important factors to consider in the context of bacterial infection and disease. Oxidative stress is one of the major weapons our immune system employs against invading bacterial pathogens, and antibiotics have been the medical treatment of choice for the last fifty years. Bacteria have evolved clever mechanisms to counteract both types of insult.

The soxRS-regulon, which has been well studied as one of the major bacterial responses to oxidative and nitrosative stress, has also been associated with chromosomally based resistance to multiple antibiotics in laboratory strains of Escherichia coli and Salmonella enterica. In the soxRS system, SoxR protein is activated by oxidation or nitrosylation to turn on transcription of the soxS gene. The SoxS protein is the direct activator of genes that provide resistance to oxidants and antibiotics.

In our lab, we have investigated the contribution of the soxRS regulon to clinical antibiotic resistance, which is an increasing problem in the treatment of infectious disease worldwide. In particular, we have shown that constitutive expression of soxRS contributes significantly to the multi-drug resistance phenotype of an S. enterica strain and that a constitutive mutation in soxR evidently arose during antibiotic treatment in that strain. We are currently conducting studies to establish the frequency with which soxRc mutations accompany antibiotic resistance in other cases of salmonellosis. We are also using genetic and biochemical methods to investigate the mechanism of constitutive soxS expression in clinical E. coli isolates and determine how such constitutive expression contributes to their multiple-antibiotic resistance phenotypes.

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