Hospital-acquired infections are a major challenge for healthcare professionals and patients, and have gained an increasing importance for overall public health. According to the Center for Disease Control and Prevention, hospital-acquired infections affect about 1.7 million people every year, and increase mortality, morbidity rates and healthcare costs. Commercially available biocides used in medical practice are not sufficient to completely decontaminate sources of nosocomial infections, including sessile biofilms with embedded pathogens, and are cytotoxic. Furthermore, antibiotics remain ineffective against multidrug resistant virulent pathogens. Therefore, a new non-toxic, broad-spectrum antimicrobial agent is needed.

Plasma medicine is rapidly growing interdisciplinary field that explores novel solutions and applications in biology and medicine. Plasma is the fourth state of matter, consists of charged particles, ions, radicals, UV photons and excited molecules and atoms. Antimicrobial effect of non-thermal plasma is characterized and the underlying mechanisms are investigated. Liquids, which are treated with non-thermal plasma acquire antimicrobial properties through the creation of plasma generated ROS and RNS and their interactions. Nacetyl cysteine (NAC) is an amino acid derivative and acquires antimicrobial property upon plasma-mediated chemical modifications.

In this thesis study, we introduce non-thermal, dielectric barrier discharge (DBD) plasma-treated NAC solution as a novel antimicrobial agent, which is non-toxic and has broad-spectrum activity against an array of multidrug resistant pathogens in their planktonic and biofilm forms. The present research also involves the detection of plasma-generated species and their products in NAC solution and their contribution in antimicrobial effect.

Damaging effects of plasma-treated NAC solution in E. coli cells are studied such as DNA damage, cell membrane damage and intracellular oxidative and nitrosative stress. In addition, most commonly reported oxidative and nitrosative stress mediated gene

activation/repression are studied in E. coli (a model organism). This study also investigates in vitro cytotoxicity and in vivo acute systemic toxicity in rats, and the stability of plasmatreated NAC solution as a part of development of novel antimicrobial solution. This study provides a better understanding of non-thermal plasma activated NAC solution and the associated chemical changes, which lead to antimicrobial effect. Nonthermal plasma- treated NAC solution is thus being explored as a new antimicrobial compound for the control of the reservoirs of nosocomial pathogens. Thus this dissertation contributes new knowledge in the field of plasma medicine and infection control.