|Organization||University of Florida|
|Topic||Biochemistry / Chem Bio.|
Discovery of Halogenated Phenazines, Hydroxyquinolines and NH125 Small Molecules as Potent Biofilm-Eradicating Agents of Gram-Positive Pathogens and MRSA Persister Cell Killers
Yasmeen Abouelhassan, Aaron T. Garrison, Akash K. Basak, Hongfen Yang, Robert W. Huigens III
University of Florida
Bacterial biofilms housing dormant persister cells are innately tolerant to many antibiotics, thus, posing a tremendous threat to human health worldwide. Chronic infections attributed to antibiotic tolerance results in an estimated 17 million biofilm infections with >500,000 annual deaths in the United States. The current clinically-used antibiotics act via inhibiting the growth of the rapidly-dividing planktonic cells. However, the majority of these antibiotics fail to inhibit and eradicate the slow-replicating bacterial biofilms. Here, we disclose the discovery of halogenated phenazines (HPs), hydroxyquinolines (HQs) and NH125 analogues that demonstrated effective biofilm eradication of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant S. epidermidis (MRSE) and vancomycin-resistant Enterococcus faecium (VRE) biofilms. HP and HQ analogues demonstrated biofilm eradication via mechanisms that involve specific metal chelation resulting in effective bacterial killing with no mammalian toxicity. On the other hand, NH125 analogues operate through membrane-lysing mechanisms and demonstrate rapid killing of MRSA persister cells. The potent biofilm eradication exhibited by HPs, HQs and NH125 analogues could have significant impact on biofilm-associated infections.