Biology subjects

Jimenez-Mejias, M. E.

Publications and source records attributed to Jimenez-Mejias, M. E..

2 recordsLinked to original sources

bioRxiv2021

Repurposing of the tamoxifen metabolites to treat methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecalis infections

Repurposing drugs provides a new approach to the fight against multidrug-resistant (MDR) bacteria. We have reported that three major tamoxifen metabolites, N-desmethyltamoxifen (DTAM), 4-hydroxytamoxifen (HTAM) and endoxifen (ENDX), presented bactericidal activity against Acinetobacter baumannii and Escherichia coli. Here, we aimed to analyse the activity of a mixture of the three tamoxifen metabolites against methicillin-resistant Staphylococcus epidermidis (MRSE) and Enterococcus spp. MRSE (n=17) and Enterococcus spp. (E. faecalis n=8, and E. faecium n=10) strains were used. MIC of the mixture of DTAM, HTAM and ENDX, and vancomycin were determined by microdilution assay. The bactericidal activity of the three metabolites together and vancomycin against MRSE (SE385 and SE742) and vancomycin-resistant E. faecalis (EVR1 and EVR2) strains was determined by time-kill curve assays. Finally, changes in membrane permeability of SE742 and EVR1 strains were analyzed using fluorescence assays. MIC50 and MIC90 of tamoxifen metabolites were 1 mg/L for MRSE strains and 2 mg/L for Enterococcus spp. strains. In the time-killing assays, tamoxifen metabolites mixture showed bactericidal activity at 2x and 4xMIC for MRSE (SE385 and SE742) and E. faecalis (EVR1 and EVR2) strains. This antimicrobial activity of tamoxifen metabolites paralleled an increased membrane permeability of SE385 and EVR2 strains. Altogether, these results showed that tamoxifen metabolites presented antibacterial activity against MRSE and vancomycin-resistant E. faecalis, suggesting that tamoxifen metabolites might increase the arsenal of drugs treatment against these bacterial pathogens.

microbiology↗

bioRxiv2020

Efficacy of lysophosphatidylcholine as direct treatment in combination with colistin against Acinetobacter baumannii in murine severe infections models

ObjectivesThe stimulation of the immune response to prevent the progression of the infection may be an adjuvant to antimicrobial treatment. Previously, we showed that preemptive treatment with lysophosphatidylcholine (LPC) in combination with colistin improved the therapeutic efficacy of colistin against MDR Acinetobacter baumannii. In this study, we aimed to evaluate the efficacy of direct treatment with LPC in combination with colistin in murine experimental models of severe infections by A. baumannii. MethodsWe used A. baumannii strain Ab9, which is susceptible to colistin and most of the antibiotics used in clinical settings, and A. baumannii strain Ab186, which is susceptible to colistin but presents a MDR pattern. The therapeutic efficacies of one and two doses of LPC (25 mg/kg/d) and colistin (20 mg/kg/8h), alone or in combination, were assessed against Ab9 and Ab186 in murine peritoneal sepsis and pneumonia models. ResultsOne and two doses of LPC in combination with colistin and colistin monotherapy enhanced bacterial clearance of Ab9 and Ab186 from spleen, lungs and blood and reduced mortality rates compared with those of the non-treated mice group in both experimental models (P<0.05). Moreover, one and two doses of LPC reduced the bacterial concentration in tissues and blood in both models, and increased mice survival in peritoneal sepsis model for both strains compared with those of colistin monotherapy group. ConclusionsLPC used as an adjuvant of colistin treatment may be helpful to reduce the severity and the resolution of the infection by MDR A. baumannii.

microbiology↗