Wang Qinqin, Wei Shaodong, Madsen Jonas Stenløkke
Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
National Food Institute, Technical University of Denmark, Kgs Lyngby, Denmark.
Commun Biol. 2025 Jul 1;8(1):968. doi: 10.1038/s42003-025-08392-2.
β-lactamases confer bacteria resistance to β-lactam antibiotics, and interestingly, this protective effect can extend to neighboring susceptible cells. However, knowledge of this cooperative resistance remains limited. Here, we investigated the underlying factors of cooperative resistance to assess commonalities and differences among the highly diverse group of β-lactamases. We first analyzed β-lactamase genes from 2637 Escherichia coli genomes, followed by experimental characterization of seven prevalent β-lactamase genes. Larger plasmids, particularly conjugative ones, commonly encoded β-lactamases. All seven genes had strong wildtype promoters, and plasmid-based expression rescued more susceptible bacteria than chromosomal expression. Cooperative resistance positively correlated with β-lactamase activity and minimal inhibitory concentrations. Cross-protection could be established between different β-lactamase producers, challenging the effectiveness of therapies combining β-lactams. Extracellular activity varied among β-lactamases and, when high, resulted in a legacy resistance effect in the environment. These findings advance our understanding of β-lactam resistance and highlight important implications for antibiotic treatment strategies.
β-内酰胺酶赋予细菌对β-内酰胺类抗生素的抗性，有趣的是，这种保护作用可扩展至邻近的敏感细胞。然而，关于这种协同抗性的认识仍然有限。在此，我们研究了协同抗性的潜在因素，以评估高度多样化的β-内酰胺酶群体之间的共性和差异。我们首先分析了2637个大肠杆菌基因组中的β-内酰胺酶基因，随后对7个常见的β-内酰胺酶基因进行了实验表征。较大的质粒，特别是接合性质粒，通常编码β-内酰胺酶。所有7个基因都有强大的野生型启动子，基于质粒的表达比染色体表达拯救了更多的敏感细菌。协同抗性与β-内酰胺酶活性和最低抑菌浓度呈正相关。不同β-内酰胺酶产生菌之间可建立交叉保护，这对β-内酰胺类联合疗法的有效性构成挑战。β-内酰胺酶的胞外活性各不相同，当其活性较高时，会在环境中产生遗留抗性效应。这些发现增进了我们对β-内酰胺抗性的理解，并突出了对抗生素治疗策略的重要意义。
