RT Journal Article
T1 Potential Tamoxifen Repurposing to Combat Infections by Multidrug-Resistant Gram-Negative Bacilli.
A1 Miró-Canturri, Andrea
A1 Ayerbe-Algaba, Rafael
A1 Del Toro, Raquel
A1 Mejías, Manuel Enrique-Jiménez
A1 Pachón, Jerónimo
A1 Smani, Younes
K1 animal model
K1 bacteria
K1 immune system
K1 infection
K1 repurposing drug
K1 tamoxifen
AB The development of new strategic therapies for multidrug-resistant bacteria, like the use of non-antimicrobial approaches and/or drugs repurposed to be used as monotherapies or in combination with clinically relevant antibiotics, has become urgent. A therapeutic alternative for infections by multidrug-resistant Gram-negative bacilli (MDR-GNB) is immune system modulation to improve the infection clearance. We showed that immunocompetent mice pretreated with tamoxifen at 80 mg/kg/d for three days and infected with Acinetobacter baumannii, Pseudomonas aeruginosa, or Escherichia coli in peritoneal sepsis models showed reduced release of the monocyte chemotactic protein-1 (MCP-1) and its signaling pathway interleukin-18 (IL-18), and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). This reduction of MCP-1 induced the reduction of migration of inflammatory monocytes and neutrophils from the bone marrow to the blood. Indeed, pretreatment with tamoxifen in murine peritoneal sepsis models reduced the bacterial load in tissues and blood, and increased mice survival from 0% to 60-100%. Together, these data show that tamoxifen presents therapeutic efficacy against MDR A. baumannii, P. aeruginosa, and E. coli in experimental models of infection and may be a new candidate to be repurposed as a treatment for GNB infections.
SN 1424-8247
YR 2021
FD 2021-05-26
LK https://hdl.handle.net/10668/27506
UL https://hdl.handle.net/10668/27506
LA en
DS RISalud
RD Apr 8, 2025