Matches in SemOpenAlex for { <https://semopenalex.org/work/W4281569276> ?p ?o ?g. }
- W4281569276 abstract "The rapid emergence of multidrug-resistant/extensively drug-resistant tuberculosis (TB) is responsible for treatment failure in patients with TB and significantly endangers global public health. Recently, bioenergetics has become a new paradigm for anti-TB drug discovery and is based on the link between bacterial ATP levels and drug efficacy. A better understanding of the role of ATP fluctuations during antibiotic treatment may provide insight into antibiotic-mediated killing of mycobacteria. Here, we employed an advanced single-fluorescence FRET (fluorescence resonance energy transfer)-based ATP biosensor, ATPser, for the stable and convenient detection of intracellular ATP fluctuations in mycobacteria. This strategy correlated closely with the results obtained from conventional luminescence ATP assays, indicating the reliability of the system for bioenergetics analysis in mycobacteria. Moreover, the reporter strains expressing ATPser displayed obvious ATP changes when subjected to different stresses, such as starvation and ATP depletion. Interestingly, we observed that different antibiotics induced fluctuations in cellular ATP levels in individual cells of various magnitudes, revealing a strong connection between ATP fluctuations and drug efficacy. Furthermore, drug combinations accelerated ATP perturbation, resulting in increased cell death. We concluded that ATPser enabled real-time measurement of ATP at the single-cell level in mycobacteria, and monitoring ATP dynamics in drug-treated bacteria may shed light on novel treatment strategies. IMPORTANCE Bioenergetics has emerged as a new paradigm for antituberculosis (anti-TB) drug discovery, and the cellular ATP level is the core indicator reflecting bacterial metabolic homeostasis. Although several bulk assays have been designed for the measurement of cellular ATP content, a more convenient strategy is required for real-time ATP measurement of single viable cells. In this study, by combining the ε-subunit of Bacillus subtilis FoF1-ATP synthase with a circularly permuted green fluorescent protein [(cp)GFP], we constructed a FRET-based single-fluorescence ATP sensor, ATPser, for real-time single-cell ATP detection among a mycobacterial population. Using the ATPser, we designed different drug combinations containing components that have similar/opposite effects on ATP alternation. Our results demonstrated that increased cellular ATP fluctuations were associated with depletion of mycobacterial viability, while counteracting ATP fluctuations weakened the killing effect of the drug regime. Thus, potentially efficient drug combinations can be considered based on their similar effects on mycobacterial ATP levels, and ATPser may be a useful tool to study mycobacterial bioenergetics and to guide drug regime design." @default.
- W4281569276 created "2022-05-27" @default.
- W4281569276 creator A5005589533 @default.
- W4281569276 creator A5011584527 @default.
- W4281569276 creator A5017343209 @default.
- W4281569276 creator A5023552292 @default.
- W4281569276 creator A5024124445 @default.
- W4281569276 creator A5034248641 @default.
- W4281569276 creator A5061273891 @default.
- W4281569276 creator A5069320466 @default.
- W4281569276 creator A5089373683 @default.
- W4281569276 date "2022-06-28" @default.
- W4281569276 modified "2023-10-18" @default.
- W4281569276 title "Single-Fluorescence ATP Sensor Based on Fluorescence Resonance Energy Transfer Reveals Role of Antibiotic-Induced ATP Perturbation in Mycobacterial Killing" @default.
- W4281569276 cites W1518907982 @default.
- W4281569276 cites W1964384820 @default.
- W4281569276 cites W1967457339 @default.
- W4281569276 cites W1968101639 @default.
- W4281569276 cites W1978009694 @default.
- W4281569276 cites W1989477034 @default.
- W4281569276 cites W1995481544 @default.
- W4281569276 cites W2005548636 @default.
- W4281569276 cites W2010457089 @default.
- W4281569276 cites W2011226772 @default.
- W4281569276 cites W2012393743 @default.
- W4281569276 cites W2042344876 @default.
- W4281569276 cites W2043130045 @default.
- W4281569276 cites W2048832265 @default.
- W4281569276 cites W2056069859 @default.
- W4281569276 cites W2083288707 @default.
- W4281569276 cites W2087779533 @default.
- W4281569276 cites W2089408860 @default.
- W4281569276 cites W2092679747 @default.
- W4281569276 cites W2110447184 @default.
- W4281569276 cites W2111887635 @default.
- W4281569276 cites W2112870272 @default.
- W4281569276 cites W2125456670 @default.
- W4281569276 cites W2129096696 @default.
- W4281569276 cites W2150740864 @default.
- W4281569276 cites W2158658436 @default.
- W4281569276 cites W2164282552 @default.
- W4281569276 cites W2168509294 @default.
- W4281569276 cites W2170021421 @default.
- W4281569276 cites W2224949521 @default.
- W4281569276 cites W2489915703 @default.
- W4281569276 cites W2586386056 @default.
- W4281569276 cites W2607441147 @default.
- W4281569276 cites W2764287995 @default.
- W4281569276 cites W2884563346 @default.
- W4281569276 cites W2885864556 @default.
- W4281569276 cites W2889969371 @default.
- W4281569276 cites W2901673575 @default.
- W4281569276 cites W2903871664 @default.
- W4281569276 cites W2906489802 @default.
- W4281569276 cites W2910579182 @default.
- W4281569276 cites W2915755236 @default.
- W4281569276 cites W2918596192 @default.
- W4281569276 cites W2952574460 @default.
- W4281569276 cites W2954214838 @default.
- W4281569276 cites W2966075625 @default.
- W4281569276 cites W2971158561 @default.
- W4281569276 cites W2981788972 @default.
- W4281569276 cites W2993404228 @default.
- W4281569276 cites W3002200482 @default.
- W4281569276 cites W3012641320 @default.
- W4281569276 cites W3084015191 @default.
- W4281569276 cites W3087383192 @default.
- W4281569276 cites W3120754026 @default.
- W4281569276 cites W3126441771 @default.
- W4281569276 cites W3137989169 @default.
- W4281569276 cites W3152566676 @default.
- W4281569276 cites W3155732227 @default.
- W4281569276 doi "https://doi.org/10.1128/msystems.00209-22" @default.
- W4281569276 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35615956" @default.
- W4281569276 hasPublicationYear "2022" @default.
- W4281569276 type Work @default.
- W4281569276 citedByCount "1" @default.
- W4281569276 countsByYear W42815692762023 @default.
- W4281569276 crossrefType "journal-article" @default.
- W4281569276 hasAuthorship W4281569276A5005589533 @default.
- W4281569276 hasAuthorship W4281569276A5011584527 @default.
- W4281569276 hasAuthorship W4281569276A5017343209 @default.
- W4281569276 hasAuthorship W4281569276A5023552292 @default.
- W4281569276 hasAuthorship W4281569276A5024124445 @default.
- W4281569276 hasAuthorship W4281569276A5034248641 @default.
- W4281569276 hasAuthorship W4281569276A5061273891 @default.
- W4281569276 hasAuthorship W4281569276A5069320466 @default.
- W4281569276 hasAuthorship W4281569276A5089373683 @default.
- W4281569276 hasBestOaLocation W42815692761 @default.
- W4281569276 hasConcept C100206155 @default.
- W4281569276 hasConcept C121332964 @default.
- W4281569276 hasConcept C12554922 @default.
- W4281569276 hasConcept C185592680 @default.
- W4281569276 hasConcept C2779564974 @default.
- W4281569276 hasConcept C2780035454 @default.
- W4281569276 hasConcept C28859421 @default.
- W4281569276 hasConcept C501593827 @default.
- W4281569276 hasConcept C55493867 @default.
- W4281569276 hasConcept C62520636 @default.
- W4281569276 hasConcept C74187038 @default.