Graduate Student Jess Mickno

"Inhibiting Bacterial Biofilms: Synthetic Peptide and Polymer Based Approaches"

Amidst a continually growing and worsening multidrug resistance crisis, an even larger threat is emerging and impacting our society today—biofilm infections. Biofilms are communities of bacteria encased in a protective coating of extracellular polymeric substance (EPS) which shields the bacteria from antibiotic drugs. Biofilm infections are 10-1000 times more antibiotic resistant than typical bacterial infections and account for 65-80% of all microbial infections1. This requires alternative strategies for treating biofilm-associated infections other than conventional antibiotic therapies.

I will present and discuss three novel approaches for inhibiting and treating biofilms. The first approach utilizes a pH-responsive fluorescent polymer that is capable of selectively targeting, detecting, imaging, and damaging biofilms2. The polymer can be used in conjunction with an antibiotic to enhance its antimicrobial activity. The second approach uses a peptidomimetic (peptide-like) polymer that is capable of inhibiting biofilm formation and disrupting established biofilms by preventing surface attachment and stimulating motility3. The final approach uses an antibiotic-peptide conjugate that is not only capable of destroying biofilms, but also stimulates the human innate immune response to combat infection4.

The antibiofilm activity and mechanism of each approach will be presented. In vivo experimentation and cytotoxicity data will also be discussed, in addition to current limitations of these approaches and possible future work.

References
1. Sharma, D.; Misba, L.; Khan, A.U. Antibiotics versus biofilm: an emerging battleground in microbial communities. Antimicrobial Resistance & Infection Control 2019, 8 (76). https://doi.org/10.1186/s13756-019-0533-3

2. Dai, X.; Xu, Q.; Yang, L.; Ma, J.; Gao, F. pH-responsive Fluorescent Polymer-Drug System for Real-Time Detection and In Situ Eradication of Bacterial Biofilms. ACS Biomater. Sci. Eng. 2022, 8, 893-902. https://doi.org/10.1021/acsbiomaterials.1c01520

3. Vishwakarma, A.; Dang, F.; Ferrell, A.; Barton, H.A.; Joy, A. Peptidomimetic Polyurethanes Inhibit Bacterial Biofilm Formation and Disrupt Surface Established Biofilms. J. Am. Chem. Soc. 2021, 143, 9440-9449. https://doi.org/10.1021/jacs.1c02324

4. Etayash, H.; Alford, M.; Akhoundsadegh, N.; Drayton, M.; Straus, S.K.; Hancock, R.E.W. Multifunctional Antibiotic-Host Defense Peptide Conjugate Kills Bacteria, Eradicates Biofilms, and Modulates the Innate Immune Response. J. Med. Chem. 2021, 64, 16854-16863. https://doi.org/10.1021/acs.jmedchem.1c01712