PMID- 34802194 OWN - NLM STAT- MEDLINE DCOM- 20220304 LR - 20230202 IS - 1864-0648 (Electronic) IS - 1864-063X (Print) IS - 1864-063X (Linking) VI - 15 IP - 2 DP - 2022 Feb TI - Inactivation of multidrug-resistant bacteria and bacterial spores and generation of high-potency bacterial vaccines using ultrashort pulsed lasers. PG - e202100207 LID - 10.1002/jbio.202100207 [doi] AB - Multidrug-resistant organisms (MDROs) represent a continuing healthcare crisis with no definitive solution to date. An alternative to antibiotics is the development of therapies and vaccines using biocompatible physical methods such as ultrashort pulsed (USP) lasers, which have previously been shown to inactivate pathogens while minimizing collateral damage to human cells, blood proteins, and vaccine antigens. Here we demonstrate that visible USP laser treatment results in bactericidal effect (>/=3-log load reduction) against clinically significant MDROs, including methicillin-resistant Staphylococcus aureus and extended spectrum beta-lactamase-producing Escherichia coli. Bacillus cereus endospores, which are highly resistant to conventional chemical and physical treatments, were also shown to be effectively inactivated by USP laser treatment, resulting in sporicidal (>/=3-log load reduction) activity. Furthermore, we demonstrate that administration of USP laser-inactivated E. coli whole-cell vaccines at dosages as low as 10(5) cfu equivalents without adjuvant was able to protect 100% of mice against subsequent lethal challenge. Our findings open the possibility for application of USP lasers in disinfection of hospital environments, therapy of drug-resistant bacterial infections in skin or bloodstream via pheresis modalities, and in the production of potent bacterial vaccines. CI - (c) 2021 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH. FAU - Tsen, Shaw-Wei David AU - Tsen SD AUID- ORCID: 0000-0002-4153-2674 AD - Department of Radiology, Washington University School of Medicine, St Louis, Missouri, USA. FAU - Popovich, John AU - Popovich J AD - The Biodesign Institute Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, Arizona, USA. FAU - Hodges, Megan AU - Hodges M AD - School of Life Sciences, Arizona State University, Tempe, Arizona, USA. FAU - Haydel, Shelley E AU - Haydel SE AUID- ORCID: 0000-0001-5542-5469 AD - The Biodesign Institute Center for Immunotherapy, Vaccines and Virotherapy, Arizona State University, Tempe, Arizona, USA. AD - School of Life Sciences, Arizona State University, Tempe, Arizona, USA. FAU - Tsen, Kong-Thon AU - Tsen KT AD - Department of Physics, Arizona State University, Tempe, Arizona, USA. AD - Center for Biophysics, Arizona State University, Tempe, Arizona, USA. FAU - Sudlow, Gail AU - Sudlow G AD - Department of Radiology, Washington University School of Medicine, St Louis, Missouri, USA. FAU - Mueller, Elizabeth A AU - Mueller EA AD - Department of Biology, Washington University in St Louis, St Louis, Missouri, USA. FAU - Levin, Petra Anne AU - Levin PA AD - Department of Biology, Washington University in St Louis, St Louis, Missouri, USA. FAU - Achilefu, Samuel AU - Achilefu S AD - Department of Radiology, Washington University School of Medicine, St Louis, Missouri, USA. AD - Department of Biochemistry and Molecular Biophysics, Washington University in St Louis, St Louis, Missouri, USA. AD - Department of Biomedical Engineering, Washington University in St Louis, St Louis, Missouri, USA. LA - eng GR - R35 GM127331/GM/NIGMS NIH HHS/United States GR - 3R01EB021048-04S1/EB/NIBIB NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20211208 PL - Germany TA - J Biophotonics JT - Journal of biophotonics JID - 101318567 RN - 0 (Bacterial Vaccines) SB - IM MH - Animals MH - Bacterial Vaccines MH - *Drug Resistance, Multiple, Bacterial MH - Escherichia coli MH - Lasers MH - *Methicillin-Resistant Staphylococcus aureus MH - Mice MH - Spores, Bacterial PMC - PMC8934174 MID - NIHMS1785479 OTO - NOTNLM OT - bacterial spores OT - multidrug-resistant organisms OT - pathogen inactivation OT - ultrashort pulsed laser OT - vaccines COIS- CONFLICTS OF INTEREST SDT and KT hold patents on "System and method for inactivating microorganisms with a femtosecond laser" (publication no. US20080299636 A1). EDAT- 2021/11/22 06:00 MHDA- 2022/03/05 06:00 PMCR- 2023/02/01 CRDT- 2021/11/21 21:06 PHST- 2021/09/20 00:00 [revised] PHST- 2021/07/08 00:00 [received] PHST- 2021/10/22 00:00 [accepted] PHST- 2021/11/22 06:00 [pubmed] PHST- 2022/03/05 06:00 [medline] PHST- 2021/11/21 21:06 [entrez] PHST- 2023/02/01 00:00 [pmc-release] AID - 10.1002/jbio.202100207 [doi] PST - ppublish SO - J Biophotonics. 2022 Feb;15(2):e202100207. doi: 10.1002/jbio.202100207. Epub 2021 Dec 8.