Pan Yu,Jia-Ning Yang,Jin-Wu Yan,Zhi-Zhong Meng,W. David Hong,Adam P. Roberts,Stephen A. Ward,Lei Zhang,Shan Li
The rapid detection of β-lactamases (Blas) and effective screening of Bla inhibitors are critically important and urgent for solving antibiotic resistance and improving precision medicine. Here a novel fluorescent probe CDC-559 was designed and synthesized, which can be used for the selective and direct detection of AmpC Blas. More importantly, it can realize screening the Bla inhibitors with sulbactam sodium and tazobactam as model compounds, and the half-maximal inhibitory concentration are 0.279 μM and 0.053 μM, respectively. CDC-559 can be applied not only to examine the resistance of bacterial strains, but also to categorize its mode of action specifically, which is consistent with the essential result of the Blas. The research suggests that CDC-559 probe has tremendous potential in the rapid detection of AmpC Blas as well as the strains with AmpC-encoded gene, which is instructive in promoting better antibiotic stewardship practices and developments.
The widespread use of antibiotics has caused the rapid emergence of antibiotic-resistant bacterial strains and antibiotic resistance genes in the past few decades. Photocatalytic inactivation, a promising approach for the killing of pathogens, efficiently avoids the problems induced by antimicrobial drugs. However, traditional photocatalysts usually have some disadvantages, such as high costs of raw materials, ultraviolet ray excitation, and potential leaching of toxic metals. Here, a metal-free heterojunction photocatalyst, denoted as CQDs/g-C 3 N 4 , is synthesized through incorporating carbon quantum dots (CQDs) on graphitic carbon nitride (g-C 3 N 4 ), which significantly enhances photocatalytic inactivation of Staphylococcus aureus ( S. aureus ) compared with pure g-C 3 N 4 in vitro. CQDs/g-C 3 N 4 causes a rapid increase of intracellular reactive oxygen species levels and destruction of cell membranes under visible light, eventually leading to death of bacteria. The efficacy of CQDs/g-C 3 N 4 is further examined by a mouse cutaneous infection model of S. aureus . CQDs/g-C 3 N 4 markedly reduces the bacterial loads and prompts lesion recovery in mice, as compared with g-C 3 N 4 -treated group. In vivo and in vitro toxicity analyses show that the side effects of CQDs/g-C 3 N 4 are negligible. Considering the efficient photocatalytic inactivation and nontoxicity of CQDs/g-C 3 N 4 , this visible-light-driven photocatalyst paves a brand new avenue for the treatment of S. aureus infection.
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