Programa de Doctorado en Biociencias Moleculares, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Centro Nacional de Biotecnología, CSIC, Darwin 3, 28049 Madrid, Spain.
Int J Mol Sci. 2022 Jan 20;23(3):1132. doi: 10.3390/ijms23031132.
The rise of multidrug-resistant Gram-negative pathogens and the lack of novel antibiotics to address this problem has led to the rescue of old antibiotics without a relevant use, such as fosfomycin. is a Gram-negative, non-fermenter opportunistic pathogen that presents a characteristic low susceptibility to several antibiotics of common use. Previous work has shown that while the so-far described mechanisms of fosfomycin resistance in most bacteria consist of the inactivation of the target or the transporters of this antibiotic, as well as the production of antibiotic-inactivating enzymes, these mechanisms are not selected in fosfomycin-resistant mutants. In this microorganism, fosfomycin resistance is caused by the inactivation of enzymes belonging to its central carbon metabolism, hence linking metabolism with antibiotic resistance. Consequently, it is relevant to determine how different growing conditions, including urine and synthetic sputum medium that resemble infection, could impact the evolutionary pathways towards fosfomycin resistance in . Our results show that is able to acquire high-level fosfomycin resistance under all tested conditions. However, although some of the genetic changes leading to resistance are common, there are specific mutations that are selected under each of the tested conditions. These results indicate that the pathways of evolution can vary depending on the infection point and provide information for understanding in more detail the routes of fosfomycin resistance evolution in .
耐多药革兰氏阴性病原体的兴起以及缺乏新型抗生素来解决这一问题，导致了旧抗生素的重新使用，比如磷霉素。是一种革兰氏阴性、非发酵机会致病菌，对几种常用抗生素表现出特征性的低敏感性。以前的工作表明，虽然迄今为止在大多数细菌中描述的磷霉素耐药机制包括该抗生素的靶标或转运蛋白的失活以及抗生素失活酶的产生，但这些机制在耐药突变体中并未被选择。在这种微生物中，磷霉素耐药性是由属于其中心碳代谢的酶失活引起的，因此将代谢与抗生素耐药性联系起来。因此，确定不同的生长条件，包括类似于感染的尿液和合成痰培养基，如何影响向 中磷霉素耐药性的进化途径是很重要的。我们的结果表明， 在所有测试条件下都能够获得高水平的磷霉素耐药性。然而，尽管导致耐药性的一些遗传变化是共同的，但在每种测试条件下都有特定的突变被选择。这些结果表明 的进化途径可能因感染部位的不同而有所不同，并为更详细地了解 中磷霉素耐药性的进化途径提供了信息。
