MCM-41 loaded with [Mn(PaPy 3 )(NO)] + for the treatment of Acinetobacter baumannii

1. MCM-41 loaded with [Mn(PaPy3)(NO)]+ for the treatment of Acinetobacter baumannii Pradip K. Mascharak, University of California- Santa Cruz, DMR 1105296 The recent emergence of extensively drug-resistant bacteria has demanded new antibiotic agents to thwart such persistent pathogens. In the current conflicts in Iraq and Afghanistan, wounded coalition soldiers have been plagued with the endemic gram-negative bacterium Acinetobacter baumannii which exhibits extensive drug-resistance. Although nitric oxide (NO) is known as a potent antimicrobial agent and bacteria seldom exhibit resistance to its action, delivery of this toxic gas selectively to infected wounds has not been possible. We have now designed a convenient NO-delivery platform in which a photoactive manganese nitrosyl has been immobilized within the channels of the biocompatible silicate-based porous material MCM-41. When this powder is applied on a soft-tissue model infected with either drug-susceptible or drug-resistant strains of A. baumannii, illumination with visible light of moderate power (equivalent to a sunny day outside) causes rapid eradication of the bacteria. This nitrosyl-containing composite material could be employed as the first line of treatment for battle-field wounds in the form of a powder that can be spayed over the infected area. Simple illumination with visible light will deliver right doses of NO to rapidly eliminate drug-resistant pathogens and aid in rapid wound healing (NO promotes angiogenesis and collagen production). Structure of the designed photoactive manganese nitrosyl Porous MCM-41 material loaded with nitrosyl within the channels Multi drug-resistant Acinetobacter baumannii isolated from the wounds of a coalition soldier Dose-dependent clearing of the bacterial load upon NO delivery through light-triggering J. Am. Chem. Soc. 2012, 134, 11573-11582

2. MCM-41 loaded with [Mn(PaPy3)(NO)]+ for the treatment of Acinetobacter baumannii Pradip K. Mascharak, University of California- Santa Cruz, DMR 1105296 Mascharak group Prof. Pradip Mascharak (PI) and Prof. Scott Oliver (Co-PI) have recently initiated this collaborative research effort in the area of biomaterials. The goal of their research effort is to design and isolate biocompatible composite materials for clinical applications. The first project is aimed at development of a user-friendly antibiotic therapy for various drug-resistant bacteria that have plagued soldiers wounded in recent conflicts around the world and in hospital-acquired infections. In a quite unconventional approach, this group has utilized the concept of NO-induced eradication of bacterial infection under the control of light. A number of graduate and undergraduate students have participated in this project (shown in the picture). This project is intimately associated with two major diversity-enhancing programs at UCSC (IMSD and MARC program). To date, three graduate and four undergraduate students of minority origin have taken active part in this project. Two international exchange students (one from Mexico and one from Brazil) have also contributed to this research. Following completion of the proof-of-the-concept experiments, the group is now actively seeking support from other agencies to further develop this therapeutic material and bring it to the clinic. This work has been highlighted in several newspapers and magazines and was displayed on the cover of the July 18th issue of the Journal of the American Chemical Society. Oliver group