Biology subjects

Cheng, J.-X.

Publications and source records attributed to Cheng, J.-X..

41 records · Page 3Linked to original sources

bioRxiv2020

Granadaene Photobleaching Reduces the Virulence and Increases Antimicrobial Susceptibility of Streptococcus agalactiae

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is increasingly recognized as a major cause of soft tissue and invasive diseases in the elderly and diabetic populations. Antibiotics like penicillin are used with great frequency to treat these infections, although antimicrobial resistance is increasing among GBS strains and underlines a need for alternative methods not reliant on traditional antibiotics. GBS hemolysin/cytolysin and granadaene pigment are two major linked virulence factors that contribute to GBS pathogenicity. Here we show that photobleaching of the antioxidant granadaene renders the pathogen more susceptible to killing by mouse macrophages and to hydrogen peroxide killing. Photo-treatment also leads to loss of activity of the linked hemolysin/cytolysin although photobleaching disproportionally affected the activity of the two factors. Treatment with light also affected GBS membrane permeability and contribute to increased susceptibility to the cell membrane active antibiotic daptomycin and to penicillin. Overall our study demonstrates a dual effect of photobleaching on the virulence and antimicrobial susceptibility of GBS and suggests a novel approach for the treatment of GBS infection. Our findings further provide new insight on the relationship between GBS hemolysin and the granadaene pigment. ImportanceFor elderly individuals or those with chronic underlying conditions (such as diabetes), skin infections caused by Streptococcus agalactiae represent a significant risk for the development of invasive disease. S. agalactiae strains are becoming increasingly resistant to antibiotics. By utilizing blue light to neutralize the granadaene pigment present in S. agalactiae, this paper presents a non-invasive and non-antibiotic reliant process capable of reducing GBS virulence while increasing the antimicrobial susceptibility of the bacterium. The differential effect of blue light on the linked GBS hemolysin/cytolysin and granadene pigment further provides new insight on the relationship between the two virulence factors. Overall photo-treatment represents a novel strategy for the treatment of S. agalactiae infections.

microbiology↗

bioRxiv2019

Photo-Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA

Confronted with the rapid evolution and dissemination of antibiotic resistance, there is an urgent need to develop alternative treatment strategies for drug-resistant pathogens. Here, we present an unconventional approach to restore the susceptibility of methicillin-resistant S. aureus (MRSA) to a broad spectrum of conventional antibiotics via photo-disassembly of functional membrane microdomains. The photo-disassembly of microdomains is based on effective photolysis of staphyloxanthin, the golden carotenoid pigment that gives its name. Upon pulsed laser treatment, 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 increases susceptibility and inhibits development of resistance to a broad spectrum of antibiotics including penicillins, quinolones, tetracyclines, aminoglycosides, lipopeptides, and oxazolidinones.\n\nOne Sentence SummaryUsing photons to crash S. aureus cell membrane and its formidable defense against a broad spectrum of antibiotics.

microbiology↗

bioRxiv2018

Rapid Determination of Antibiotic Susceptibility by Stimulated Raman Scattering Imaging of D2O Metabolism

Rapid antibiotic susceptibility testing (AST) is urgently needed for treating infections with correct antibiotics and slowing down the emergence of antibiotic resistant bacteria. Current clinical methods reply on culture and take at least 16 h. Here, using P. aeruginosa, E. coli and S. aureus as models, we show that the AST can be finished in 10 minutes by stimulated Raman scattering (SRS) imaging of D2O metabolic activities. The metabolic incorporation of D2O, which is used for biomolecule synthesis, can be monitored in a single bacterium. Time lapse experiments show that the C-D vibrational signal can be observed in a single bacterium within 10 minutes culture in D2O medium. Since water is universally used for biosynthesis in bacteria, SRS imaging of D2O metabolism has the potential to be generalizable to different bacteria species.

microbiology↗

bioRxiv2018

Optoacoustic brains stimulation at submillimeter spatial precision

Low-intensity ultrasound is an emerging modality for neuromodulation. Yet, piezo-based transducers offer poor spatial confinement of excitation volume, often bigger than a few millimeters in diameter. In addition, the bulky size limits their implementation in a wearable setting and prevents integration with other experimental modalities. Here, we report spatially confined optoacoustic neural stimulation through a novel miniaturized Fiber-Optoacoustic Converter (FOC). The FOC has a diameter of 600 m and generates omnidirectional ultrasound wave locally at the fiber tip through the optoacoustic effect. We show that the optoacoustic wave can directly activate individual cultured neurons and generate intracellular Ca2+ transients. The FOC activates neurons within a radius of 500 m around the fiber tip, delivering superior spatial resolution over conventional piezo-based low-frequency transducers. Combining FOC with electrophysiology, direct and spatially confined neural stimulation of mouse brain is achieved in vivo.

neuroscience↗

bioRxiv2017

Annihilation of Methicillin-resistant Staphylococcus aureus via Photobleaching of Staphyloxanthin

Given that the dearth of new antibiotic development loads an existential burden on successful infectious disease therapy1, health organizations are calling for alternative approaches to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report a drug-free photonic approach to eliminate MRSA through photobleaching of staphyloxanthin, an indispensable membrane-bound antioxidant of S. aureus2-5. The photobleaching process, uncovered through a transient absorption imaging study and quantitated by absorption spectroscopy and mass spectrometry, decomposes staphyloxanthin and sensitizes MRSA to reactive oxygen species attack. Consequently, staphyloxanthin bleaching by low-level blue light eradicates MRSA synergistically with external or internal reactive oxygen species. The effectiveness of this synergistic therapy is validated in MRSA culture, MRSA-infected macrophage cells, S. aureus biofilms, and a mouse wound infection model. Collectively, these findings highlight broad applications of staphyloxanthin photobleaching for treatment of MRSA infections.

microbiology↗