Since antibiotics and antimicrobial drugs were first available some 70 years ago, they have saved countless lives and became among modern medicine's greatest achievement. However, in the past few years, disease-causing microorganisms that have become resistant to drug therapy have emerged as a serious threat to military personnel and wounded soldiers as well as to the general public. Multidrug-resistant infections, which frequently develop after battlefield trauma, are particularly devastating in Wounded Warriors suffering from burns, blast wounds, and bone injuries. These infections cause severe negative outcome to the soldier and frequently lead to bone infection, limb losses, and possible death. In addition, bacteria that infect combat-related wounds could easily be spread to other patients and staff in military and civilian medical facilities. It is estimated that in the United States alone nearly 2 million patients get hospital-acquired infection annually with more than 70 percent of the infections caused by bacteria resistant to at least one of the antibiotics commonly used to treat them.

With the emergence of new multidrug-resistant bacteria, the need for discovering new antimicrobials has become increasingly urgent. Throughout millions of years of evolution, bacteria have developed a vast array of mechanisms that allowed them to survive in their environment, including the secretion of antibiotics and other biologically active compounds. We hypothesize that surface attached bacteria, known as biofilms, produce natural compounds that help them to survive and compete in their environment. We have also established that these compounds could be readily isolated from biofilms. The objective of this proposal is to isolate novel antimicrobial and antibiofilm compounds from within established biofilms. To this end, a diverse collection of microorganisms will be assembled and examined for their ability to produce antimicrobial and antibiofilm compounds that are active specifically against clinically relevant multidrug-resistant pathogens.

Despite the World Health Organization listing antibiotic resistance as one of the top three health threats the world faces, little has been done to address the issue. In this study, we propose to go back to the indisputable success of early microbiology and re-tap into the unlimited potential of bacteria to produce antimicrobial compounds. By exploiting the biofilm's distinctive ability to accumulate and produce unique secondary metabolites, we aim to identify novel antimicrobial and antibiofilm compounds. The proposed experiments are expected to lead to the discovery of new antimicrobial and antipathogenic-biofilm countermeasures that might be used systemically or topically for treating Wounded Warriors and civilians. We trust that the new compounds will have the potential to significantly reduce the incidence and severity of wound-related infections, reduce the transmission of wound-associated bacteria in military hospitals, prevent the transmission of bacterial infections in civilian hospitals, and "re-infuse" medical caregivers with new antimicrobials that are urgently needed to save civilian and military personnel.