Reactive oxygen species-dependent anti-extended spectrum β-lactamases activity of multi-layer Ti3C2Tx: A novel approach for treating successfully P. aeruginosa and K. pneumoniae

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2024-11, Vol.500, Article 157111
• Main Authors: Rajivgandhi, Govindan, Mudaliar Mahesh Margoni, Kanisha Chelliah, Chenthis, Rosenkranz, Andreas, Gnanasekaran, Chackaravarthi, Ramachandran, Vijayan, Ramachandran, Govindan, Bhuyan, Heman, Adell, José F., Maruthupandy, Muthuchamy, Manoharan, Natesan, Ali Akbari-Fakhrabadi, Quero, Franck
• Format: Article
• Language: English
• Subjects: Antagonistic activity; Molecular docking; Multi-layer Ti3C2Tx; MXene; Pathogenicity inactivation; Toxicity evaluation; β-lactamase inhibition
• ISSN: 1385-8947
• DOI: 10.1016/j.cej.2024.157111

[Display omitted] •ML-Ti3C2Tx induced increasing oxidative stress for inactivation of β-lactamases.•ROS were produced in response to oxidative stress and β-lactamase resistance.•Membrane damages and wrinkled surface indicated compromised bacterial cells.•Low mortality rate of brine animal Artemia suggested ML-Ti3C2Tx as non-toxic material. Multi-layer (ML) Ti3C2Tx was investigated regarding its anti-extended spectrum β-lactamases (ESBLs) activity and in-vivo toxicity. Powder X-ray diffraction of ML-Ti3C2Tx confirmed the successful etching of Ti3AlC2 (MAX) to form ML-Ti3C2Tx as well as the presence of –OH, −F and −O surface terminations. Fourier-transform infrared spectroscopy and thermal decomposition verified the presence of its typical chemical bonds and moieties including Ti-O, O–H, C–H, CO, and –OH, which further confirmed the successful synthesis of ML-Ti3C2Tx. Scanning and transmission electron microscopy demonstrated its multi-layered structure, while X-ray photoelectron spectroscopy revealed the presence of various photoelectron peaks with binding energy positions corresponding to O1s, C1s, Ti2p, and F1s, indicating the existence of distinct surface terminations and oxidation states. The E-strip synergy and micro-iodometric methods suggested that ML-Ti3C2Tx possesses excellent β-lactamases inactivation with 96 and 94 % inhibition at 90 µg/mL against P. aeruginosa (MN310553) and K. pneumoniae (MN368594), respectively. Concentration-dependent reactive oxygen species (ROS) generation of ML-Ti3C2Tx decreased notably bacterial cell growth as well as its response to β-lactamase resistances. Moreover, intercellular damage and outer cell wall rupture through external proliferation forces of sharp-edged ML-Ti3C2T were confirmed by confocal laser and scanning electron microscopy. Molecular docking suggested that Ti3C2Tx induced effective inhibition of TEM1 β-lactamase, providing insights for future development of drug-resistant ESBLs with gene control. Finally, the evaluation of the in-vivo toxicity of the synthesized ML-Ti3C2Tx against brine shrimp Artemia revealed their non-toxicity up to a maximum concentration of 150 µg/mL and 24 h exposure time.