RESUMEN

Estrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid Pseudomonas aeruginosa in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study, we demonstrate that at physiological concentrations, sex steroids, including testosterone and estriol, induce membrane stress responses in P. aeruginosa This is characterized by increased virulence and consequent inflammation and release of proinflammatory outer membrane vesicles promoting in vivo persistence of the bacteria. The steroid-induced P. aeruginosa response correlates with the molecular polarity of the hormones and membrane fluidic properties of the bacteria. This novel mechanism of interaction between sex steroids and P. aeruginosa explicates the reported increased disease severity observed in females with cystic fibrosis and provides evidence for the therapeutic potential of the modulation of sex steroids to achieve better clinical outcomes in patients with hormone-responsive strains.IMPORTANCE Molecular mechanisms by which sex steroids interact with P. aeruginosa to modulate its virulence have yet to be reported. Our work provides the first characterization of a steroid-induced membrane stress mechanism promoting P. aeruginosa virulence, which includes the release of proinflammatory outer membrane vesicles, resulting in inflammation, host tissue damage, and reduced bacterial clearance. We further demonstrate that at nanomolar (physiological) concentrations, male and female sex steroids promote virulence in clinical strains of P. aeruginosa based on their dynamic membrane fluidic properties. This work provides, for the first-time, mechanistic insight to better understand and predict the P. aeruginosa related response to sex steroids and explain the interindividual patient variability observed in respiratory diseases such as cystic fibrosis that are complicated by gender differences and chronic P. aeruginosa infection.

Asunto(s)

Membrana Externa Bacteriana/efectos de los fármacos , Fibrosis Quística/complicaciones , Hormonas Esteroides Gonadales/metabolismo , Pseudomonas aeruginosa/patogenicidad , Estrés Fisiológico/efectos de los fármacos , Alginatos/metabolismo , Animales , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Fibrosis Quística/microbiología , Estradiol/química , Estradiol/farmacología , Femenino , Hormonas Esteroides Gonadales/farmacología , Humanos , Inflamación , Masculino , Ratones , Ratones Endogámicos BALB C , Pseudomonas aeruginosa/genética , Factores Sexuales , Testosterona/química , Testosterona/farmacología , Virulencia

RESUMEN

OBJECTIVE: Septoplasty has been the definitive treatment for nasal septum deviation, but its postoperative procedure may affect patients' quality of life. While new procedures in general surgery, such as enhanced recovery after surgery (ERAS), can speed up postoperative rehabilitations to improve quality of life, it is rarely applied in the ear-nose-throat field. This study therefore aims to evaluate the application of ERAS in patients with nasal septum deviation as a means of improving perioperative outcomes. MATERIALS AND METHODS: Fifty patients with nasal septum deviation undergoing septoplasty were randomized as ERAS or control group (25 patients in both groups). Patients were investigated for outcomes including length of stay, operating time, bleeding volume, total cost, complications, and Self-Rating Anxiety Scale (SAS) and visual analog symptom score of nasal obstruction, sleep disturbance, and head facial pain. RESULTS: The preoperative anxiety in ERAS group (SAS 35.4±6.2) was lower than the control group (SAS 43.6±8.6). The anxiety levels in ERAS group (SAS 31.6±5.4) was also reduced compared to the control group (SAS 38.1±10.4) in the 3 days postsurgery, but showed no significant difference thereafter at 7 days postsurgery. In addition, the length of stay and total cost were significantly lower for the ERAS group as well. The visual analog symptom score of nasal obstruction, sleep disturbance, and head facial pain in ERAS group were all also found to be lower than the control group. The only outcomes with no significant differences were the operation time, blood volume, and complications between the groups. CONCLUSION: Our study indicated ERAS application can reduce hospital charges and postoperative pain in septoplasty, thereby improving patient quality of life and hospital expenses at the same time.