Novel Zinc containing Porphyrin exhibits dark toxicity against an opportunistic pathogenic bacterium grown under planktonic and biofilm conditions

Title

Novel Zinc containing Porphyrin exhibits dark toxicity against an opportunistic pathogenic bacterium grown under planktonic and biofilm conditions

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Description

One of the greatest threats to human health, and life, is the rise of antibiotic resistant bacterial infections. National summary data from the CDC estimates that at least 2,049,442 million illnesses and 23,000 deaths occur each year as the result of antibiotic resistant bacteria and fungi. Additionally, 250,000 illnesses and 14,000 deaths are caused by the bacterium Clostridium difficile, considered to be related to antibiotic resistance and use. We are the co-inventors of two patented novel technologies for the treatment of antibiotic resistant bacteria. Both treatments make use of a novel porphyrin ZnP (US Patent # 9,364,537) that does not require using traditional photo-activation i.e., it exhibits unique dark toxicity. In standard tests against planktonic cells ZnP exhibits broad spectrum activity, for example it is bactericidal towards: Pseudomonas aeruginosa (MIC90 at 25µM), MSSA and MRSA strains of Staphylococcus aureus, as well as Listeria monocytogenes and Mycobacterium smegmatis. In toxicity testing using lung alveolar cells no toxicity was detected at concentrations that were 2-fold higher than the MIC. We have demonstrated that P. aeruginosa (PAO1) cells take up ZnP rapidly and accumulate it inside the cell. In cells treated with 25 µM ZnP there was a substantial loss of chromosomal DNA after as little as 5h; with an almost total loss at 50 µM. Additionally, we have tested various uptake/transport systems in PAO1 that aid in uptake of ZnP. In biofilm experiments, ZnP was able to disrupt 16h preformed biofilms on Polyethylene (PE) and stainless steel surfaces by 2 logs and, more interestingly, prevent the formation of biofilms when PE surface was pretreated with 25µM ZnP compared to the control.

Publication Date

4-18-2018

Project Designation

Graduate Research

Primary Advisor

Kristen Krupa Comfort, Jayne B Robinson, Shawn M Swavey

Primary Advisor's Department

Biology

Keywords

Stander Symposium poster

Comments

Presenter: Nehaben Nik Patel

Novel Zinc containing Porphyrin exhibits dark toxicity against an opportunistic pathogenic bacterium grown under planktonic and biofilm conditions

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