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<p>Emergence of antibiotic resistance has become an increasing public health concern worldwide. All our current understanding about the genetics and evolution of antibiotic-resistance is based on the selections of rare mutants with strong phenotypes when exposed to lethal concentrations of drugs. But this may not be the case under natural environments in which foodborne pathogenic bacteria may be frequently exposed to concentration gradients of antibiotics or sublethal concentrations of various acids, alkali, heat or oxidative stress that may put selection pressure prior to antibiotic exposure. Under those sublethal environments, any resistance mutations if induced are rapidly enriched upon coming in contact with low antibiotic concentrations which may lead to a step-wide development of antibiotic resistance. Keeping this hypothesis in view, we will measure the degree and stability of increase or decrease in resistance in diverse strains of two foodborne bacterial pathogens, Gram-positive Listeria monocytogenes and Gram-negative Salmonella strains, against selected antibiotics after their adaption to sublethal acid, alkali, and oxidative stress environments prior to exposure to antibiotics with the following objectives:</p><p>Objective 1. Determine the degree and stability of resistance to ampicillin, amoxicillin, and trimethoprim/sulfamethoxazole in genetically diverse L. monocytogenes serotypes isolated from fresh fruits and vegetables, dairy and poultry products after exposure to sublethal acid, alkali and oxidative stress environments.</p><p>Objective 2. Determine the degree and stability of resistance to ceftriaxone, ciprofloxacin, and trimethoprim/sulfamethoxazole in genetically diverse Salmonella serotypes isolated from fresh fruits and vegetables, dairy and poultry products after exposure to sublethal acid, alkali and oxidative stress environments. </p>
The factors that accelerate the emergence and spread of antibiotic-resistant bacteria in humans, animals and in the environment are not clearly established. Recent evidence suggests that sublethal concentrations of antibiotics play an important role in the evolution of antibiotic resistance. However, all our current understanding about the genetics and evolution of antibiotic-resistance is based on the selections of rare mutants with strong phenotypes when exposed to lethal concentrations of drugs. But this may not be the case under natural environments in which foodborne pathogenic bacteria may be frequently exposed to concentration gradients of antibiotics. Also, foodborne bacterial pathogens may be exposed to sublethal concentrations of various acids, alkali, heat or oxidative stress that may put selection pressure prior to antibiotic exposure. Under sublethal environments, any resistance mutations if induced are rapidly enriched upon coming in contact with low antibiotic concentrations which may lead a step-wide development of antibiotic resistance. Keeping this hypothesis in view, we will measure the degree and stability of increase or decrease in resistance in diverse strains of two foodborne bacterial pathogens, Listeria monocytogenes and Salmonella strains, against selected antibiotics after their exposure to sublethal acid, alkali, and oxidative stress environments prior to exposure to lethal antibiotics. This study will lead to important evidence on the role sublethal acid, alkali, oxidative and heat stress that may be prevalent in food production and processing environments on the emergence of antibiotic cross-resistance risk in foodborne bacterial pathogens. We will detect hypermutable clones that exhibit antibiotic resistance. On September 18, 2014, an executive order has been signed by the President of the United States on combating antibiotic-resistant bacteria. A new task force has been setup to detect, prevent, and control illness and death related to antibiotic-resistant infections by implementing measures that reduce the emergence and spread of antibiotic-resistant bacteria. Our work will demonstrate the linkage between unintended mild stress exposure leading to antibiotic-resistant phenotypes of L. monocytogenes and Salmonella in food production and processing environments. Our work will determine the sublethal triggers for stress-hardened L. monocytogenes and Salmonella in high-risk serotypes that may lead to emergence of highly stable antibiotic resistance clones. This will lead to improvements in risk analysis and subsequent intervention technologies for various food production and processing systems for elimination of these emerging antibiotic resistant foodborne bacterial pathogens.