Bacterial infections are a major healthcare concern. Clinical application of photo‐activated quantum dots to efficiently treat bacterial infections has been hindered by inadequate production of reactive oxygen species. In this study, photoactive antimicrobial carboxyl‐functionalized graphene quantum dots (cGQDs) are synthesized with an exceptionally high singlet oxygen (1O2) quantum yield of 0.88. Compared to non‐functionalized GQDs, cGQDs exhibit over a 20‐fold enhancement in the 1O2 quantum yield. According to the density functional theory simulations, the dramatic increase of 1O2 quantum yield is due to significantly enhanced spin–orbit coupling between singlet and triplet excited states of GQDs with addition of ─COOH groups. Under low‐intensity blue light (5 mW cm−2), Staphylococcus aureus is completely eliminated with just 0.8 µg mL−1 of cGQDs, and a minimum bactericidal concentration (MBC) of 0.4 µg mL−1 is determined, representing the lowest MBC reported against S. aureus using light‐activated quantum dots. Layer‐by‐layer assembly of cGQD films also results in over a 99.9% reduction against multi‐drug resistant Staphylococcus aureus and Escherichia coli under illumination. cGQDs, both in suspension and as a nano‐assembled film, exhibit good cell viability in mammalian cells under both dark and light conditions. These results highlight the strong potential of cGQDs as an effective nanomaterial for antibacterial applications.
Staphylococcus aureus and Staphylococcus epidermidis are related species which can cause predominantly acute and subacute infections, respectively. Differences in human adaptive immune responses to these two species are not well understood. Dendritic cells (DCs) have an important role in the control and regulation of anti-staphylococcal T cell responses. Therefore, we aimed to compare the ability of S. aureus and S. epidermidis to influence the essential steps in human DC activation and subsequent antigen-specific CD4+ T cell proliferation, and to investigate the underlying mechanisms. Using multiple strains of both species, we observed that S. aureus was internalized more effectively than S. epidermidis by DCs but that both species were equally potent in activating these host cells, as evidenced by similar induction of DC maturation marker expression and antigen loading onto MHC-II molecules. The DCs stimulated by S. aureus strains not harboring superantigen (SAg) genes or by any of the S. epidermidis strains, induced low, likely physiological levels of T cell proliferation. Only DCs stimulated with S. aureus strains harboring SAg genes induced high levels of T cell proliferation. Taken together, S. aureus and S. epidermidis do not differently affect DC activation and ensuing antigen-specific T cell proliferation, unless a strain has the capacity to produce SAgs.
Bioactive glass (BAG) S53P4 is a clinically approved bone substitute with antibacterial, osteoconductive and osteostimulatory properties. Its antibacterial effect is associated with ion release, local pH elevation and osmolality, but the precise biochemical and biophysical mode-of-action is unclear. This study investigates the antibacterial mechanism of BAG S53P4 eluates. BAG eluates, collected at 2, 4, 8, and 24 h, eradicated Staphylococcus aureus. Elemental analysis revealed an early increase in concentrations of Si and Na, a later rise in Ca, depletion of P over time and rapid loss of Mg. Membrane disturbances occurred within 5 min, evident by permeability for SYTOX, aligning with time-kill kinetics for S. aureus and Bacillus subtilis. In B. subtilis, 2h-BAG-eluate induced rapid delocalization of marker proteins for cell division and DNA repair, signaling membrane potential collapse and nucleoid condensation. Transcriptomics revealed early transcription remodeling reflecting ionic and energetic imbalance, including disruption of central metabolism, redox homeostasis, and translational stability. Scanning electron microscopy revealed severe cell surface damage and particulate deposits on S. aureus. Transmission electron microscopy showed cell envelop disruptions and cytoplasmic leakage. Energy dispersive X-ray analysis identified Si on bacterial cell surface at 4 h and intracellular accumulation in punctured, empty cells at 24 h. Overall, BAG ionic dissolution products kill bacteria through a stepwise mechanism involving membrane damage, protein delocalization and metabolic impairment, accompanied by Si deposition on bacterial surfaces and loss of Mg. This finally leads to cell wall degradation, cytoplasmic content leakage and further Si deposition on the cells and inside cell ghosts.
Candidozyma auris is an emerging opportunistic fungal pathogen that can cause serious catheter-related blood stream infections associated with high morbidity and mortality. The traditional antifungal treatment with polyenes, azoles or echinocandins is becoming less effective due to both intrinsic and developed resistance, complicating treatment. This study demonstrates the potent fungicidal activity of carboxyl-functionalized graphene quantum dots (cGQDs) against a panel of C. auris strains, spanning clades I to V, and a Candida albicans reference strain. Photoactivation of cGQDs in suspension with 435 nm blue light killed 99.9% of the fungi within 30 min even though the majority of test strains were resistant to at least one conventional antifungal. Moreover, cGQDs coated on flexible polydimethylsiloxane surfaces and commercial catheters via electrostatic layer-by-layer deposition with alternating positively charged polydiallyldimethylammonium polymer showed strong fungicidal activity against C. auris and C. albicans. These findings show that the cGQDs, both in suspension and in a thin film coating, have potential for future clinical development. In particular, their application to catheters may help prevent Candidozyma and Candida catheter-related infections.