Abstract
Bacterial resistance to antibiotics have become one of the most severe threats in global public health, so the development of new-style antimicrobial agents is urgent. In this work, quaternized carbon quantum dots (qCQDs) with broad-spectrum antibacterial activity were synthesized by a simple green “one-pot” method using dimethyl diallyl ammonium chloride and glucose as reaction precursors. The qCQDs displayed satisfactory antibacterial activity against both Gram-positive and gram-negative bacteria. In rat models of wounds infected with mixed bacteria, qCQDs obviously restored the weight of rats, significantly reduced the death of rats from severe infection, and promoted the recovery and healing of infected wounds. Biosafety tests confirmed that qCQDs had no obvious toxic and side effects during the testing stage. The analysis of quantitative proteomics revealed that qCQDs mainly acted on ribosomal proteins in Staphylococcus aureus (Gram-positive bacteria) and significantly down-regulated proteins associated with citrate cycle in Escherichia coli (Gram-negative bacteria). Meanwhile, real-time quantitative PCR confirmed that the variation trend of genes corresponding to the proteins associated with ribosome and citrate cycle was consistent with the proteomic results after treatment of qCQDs, suggesting that qCQDs has a new antibacterial mechanism which is different from the reported carbon quantum dots with antibacterial action. Statement of significanceWith the development of the research on carbon quantum dots, the application of carbon quantum dots in the field of medicine has attracted extensive attention. In this paper, quaternized carbon quantum dots (qCQDs) with antimicrobial activity prepared by specific methods were studied, including antimicrobial spectrum, antimicrobial mechanism and in vivo antimicrobial application. The antimicrobial mechanism of qCQDs was studied by proteomics and RT-qRCR, and the different mechanisms of qCQDs against Gram-positive and Gram-negative bacteria were also found. This study provides a research foundation for the application of carbon quantum dots in antimicrobial field, and also expands the application range of carbon quantum dots in medicine field.
Highlights
There is no doubt that bacterial infectious diseases have always posed a serious threat to human health and are always a sever challenge for medical workers
The particle size of Quaternized carbon quantum dots (qCQDs) measured by dynamic light scattering (DLS) was centered at 4.5 nm with relatively concentrated distribution, suggesting the consistent and uniform morphology of qCQDs confirmed from Transmission electron microscope (TEM)
It was confirmed by TEM that qCQDs could destroy the integrity of bacterial structure, make the substances inside the cell agglomerate and leak, and result in the death of bacteria
Summary
There is no doubt that bacterial infectious diseases have always posed a serious threat to human health and are always a sever challenge for medical workers. With the widespread and extensive use of antibiotics for the last 70 years or so, antimicrobial resistance (AMR) has become an imminent threat to the effective treatment of bacterial infections. Novel antimicrobial agents against severely resistant bacteria are urgently needed to address the problem. In response to increasing antibiotic resistance in bacteria, alternatives different from traditional antibiotics are being investigated, including antibodies, probiotics, bacteriophages and antimicrobial peptides currently undergoing clinical trials, and advancements within artificial intelligence, biotechnology, genetic engineering and synthetic chemistry have opened up new avenues towards the search for therapies that can substitute for antibiotics[3, 4]. Extensive use of these alternatives is limited by the cost of production and limited shelf life, and the potential biotoxicity and the occurrence of new bacterial resistance always puzzle the application of various new technologies in research and development of antimicrobial drug. It is still an urgent task to clarify the molecular mechanism of antibacterial and avoid new bacterial resistance
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