公开(公告)号：US11013933B2

公开(公告)日：2021-05-25

申请号：US16139127

申请日：2018-09-24

Applicant: Purdue Research Foundation

Inventor： Ji-Xin Cheng ,  Mohamed Seleem ,  Pu-Ting Dong ,  Jie Hui

IPC: A61N5/06 ,  C12N13/00 ,  A61K31/546 ,  A61K31/7036 ,  A61K31/496 ,  A61K38/12 ,  A61K31/431 ,  A61N5/067

Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) possesses array of strategies to evade antibiotics through mutational inactivation, hiding inside host immune cells or concealing inside the biofilm in a sessile form. We report a drug-free approach to eradicate MRSA through blue-light bleaching of staphyloxanthin (STX), an anti-oxidative carotenoid residing inside the cell membrane of S. aureus. The photobleaching process, uncovered through a transient absorption imaging study and quantitated by mass spectrometry, decomposes STX and sensitizes MRSA to reactive oxygen species attack. Consequently, photobleaching using low-level blue light exhibits high-level synergy when combined with low-concentration of hydrogen peroxide. Antimicrobial effectiveness of this synergistic therapy is validated in MRSA culture, MRSA-infected macrophage cells, biofilm, and a mouse wound infection model. Collectively, these findings highlight broad applications of STX photobleaching for MRSA-infected diseases.

公开(公告)号：US20190126063A1

公开(公告)日：2019-05-02

申请号：US16139127

申请日：2018-09-24

Applicant: Purdue Research Foundation

Inventor： Ji-xin Cheng ,  Mohamed Seleem ,  Pu-Ting Dong ,  Jie Hui

IPC: A61N5/06 ,  A61K31/546 ,  A61K31/7036 ,  A61K31/496 ,  A61K31/431 ,  A61K38/12 ,  C12N13/00

Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) possesses array of strategies to evade antibiotics through mutational inactivation, hiding inside host immune cells or concealing inside the biofilm in a sessile form. We report a drug-free approach to eradicate MRSA through blue-light bleaching of staphyloxanthin (STX), an anti-oxidative carotenoid residing inside the cell membrane of S. aureus. The photobleaching process, uncovered through a transient absorption imaging study and quantitated by mass spectrometry, decomposes STX and sensitizes MRSA to reactive oxygen species attack. Consequently, photobleaching using low-level blue light exhibits high-level synergy when combined with low-concentration of hydrogen peroxide. Antimicrobial effectiveness of this synergistic therapy is validated in MRSA culture, MRSA-infected macrophage cells, biofilm, and a mouse wound infection model. Collectively, these findings highlight broad applications of STX photobleaching for MRSA-infected diseases.

公开(公告)号：US20200306295A1

公开(公告)日：2020-10-01

申请号：US16580113

申请日：2019-09-24

Applicant: Purdue Research Foundation

Inventor： Ji-xin Cheng ,  Mohamed Seleem ,  Pu-Ting Dong ,  Jie Hui

IPC: A61K33/40 ,  A61L2/00 ,  A61L2/26 ,  A61P31/04 ,  A61K31/7028

Abstract: Confronted with the rapid evolution and dissemination of antibiotic resistance, there is an urgent need to develop alternative treatment strategies for drug-resistant S. aureus, especially for methicillin-resistant S. aureus (MRSA). We report a photonic approach to eradicate MRSA through blue-light photolysis of staphyloxanthin (STX), an anti-oxidative carotenoid acting as the constituent lipid of the functional membrane microdomains of S. aureus. Our transient absorption imaging study and mass spectrometry unveil the photolysis process of STX. After effective STX photolysis by pulsed laser, cell membranes are found severely disorganized and malfunctioned to defense antibiotics, as unveiled by membrane permeabilization, membrane fluidification, and detachment of membrane protein, PBP2a. Consequently, our photolysis approach sensitizes MRSA to reactive oxygen species attack and increases susceptibility and inhibits development of resistance to a broad spectrum of antibiotics including penicillins, quinolones, tetracyclines, aminoglyco sides, lipopeptides, and oxazolidinones. The synergistic therapy, without phototoxicity to the host, is effective in combating MRSA both in vitro and in vivo in a mice skin infection model. Collectively, this staphyloxanthin-targeted phototherapy concept paves a novel platform to use conventional antibiotics as well as reactive oxygen species to combat multidrug-resistant S. aureus infections.

公开(公告)号：US11109763B2

公开(公告)日：2021-09-07

申请号：US15998889

申请日：2017-02-13

Applicant: PURDUE RESEARCH FOUNDATION

Inventor： Ji-xin Cheng ,  Pu Wang ,  Yingchun Cao ,  Jie Hui

IPC: A61B5/00 ,  A61B8/00 ,  A61B5/02 ,  A61B8/12 ,  A61M25/00

Abstract: A photoacoustic catheter includes an elongated catheter body and a housing positioned near a distal end of the elongated catheter body. A length of multimode fiber extends through the elongated catheter body and has a distal end that is beveled at about 45° relative to a longitudinal axis of the multimode fiber and is positioned in the housing. An ultrasonic transducer, electrically connected to an electrical wire extending along the elongated catheter body, is positioned within the housing. A mirror element is also positioned within the housing and includes a mirror surface beveled at about 45° relative to the longitudinal axis of the multimode fiber. The catheter is operable to deliver an optical wave through the multimode fiber and to deliver an ultrasonic wave collinearly from the housing and out of an aperture of the housing to obtain optical data and ultrasonic data within a mammalian luminal organ.