Fosfomycin Resistance Evolutionary Pathways of Stenotrophomonas maltophilia in Different Growing Conditions

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. <i>Stenotrophomonas maltophilia</i> is a Gram-negative, non-fermenter opportunistic patho...

ver descrição completa

Detalhes bibliográficos
Autores: Gil-Gil, Teresa, Martínez, J. L.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/262894
Acesso em linha:http://hdl.handle.net/10261/262894
Access Level:acceso abierto
Palavra-chave:Stenotrophomonas maltophilia
Experimental evolution
Fosfomycin resistance
Descrição
Resumo: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. <i>Stenotrophomonas maltophilia</i> 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 <i>S. maltophilia</i> 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 <i>S. maltophilia</i>. Our results show that <i>S. maltophilia</i> 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 <i>S. maltophilia</i> evolution can vary depending on the infection point and provide information for understanding in more detail the routes of fosfomycin resistance evolution in <i>S. maltophilia</i>.