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Article

UNAM-HIMFG Bacterial Lysate Activates the Immune Response and Inhibits Colonization of Bladder of Balb/c Mice Infected with the Uropathogenic CFT073 Escherichia coli Strain

by
Salvador Eduardo Acevedo-Monroy
1,2,
Ulises Hernández-Chiñas
1,3,*,
Luz María Rocha-Ramírez
4,
Oscar Medina-Contreras
5,
Osvaldo López-Díaz
6,
Ricardo Ernesto Ahumada-Cota
1,
Daniel Martínez-Gómez
7,
Sara Huerta-Yepez
8,
Ana Belén Tirado-Rodríguez
8,
José Molina-López
1,3,
Raúl Castro-Luna
9,
Leonel Martínez-Cristóbal
9,
Frida Elena Rojas-Castro
1,
María Elena Chávez-Berrocal
1,3,
Antonio Verdugo-Rodríguez
2 and
Carlos Alberto Eslava-Campos
1,3,*
1
Laboratorio de Patogenicidad Bacteriana, Unidad de Hemato-Oncología e Investigación, Hospital Infantil de México “Federico Gómez”, Dr. Márquez No. 162, Col Doctores, Alcaldía Cuauhtémoc, Ciudad de México 06720, Mexico
2
Laboratorio de Microbiología Molecular, Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México., Av. Universidad #3000, Colonia, C.U., Coyoacán, Ciudad de México 04510, Mexico
3
Unidad Periférica de Investigación Básica y Clínica en Enfermedades Infecciosas, Departamento de Salud Pública, División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, Dr. Márquez No. 162, Col Doctores, Alcaldía Cuauhtémoc, Ciudad de México 06720, Mexico
4
Unidad de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Dr. Márquez No. 162, Col Doctores, Alcaldía Cuauhtémoc, Ciudad de México 06720, México
5
Unidad de Investigación Epidemiológica en Endocrinología y Nutrición, Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Col. Doctores, Alcaldía Cuauhtémoc, Ciudad de México 06720, México
6
Laboratorio de Histopatología Veterinaria, Universidad Autónoma Metropolitana Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, Alcaldía Coyoacán, Ciudad de México 04960, México
7
Departamento de Producción Agrícola y Animal, Laboratorio de Microbiología Agropecuaria, Universidad Autónoma Metropolitana Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, Alcaldía Coyoacán, Ciudad de México 04960, México
8
Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México, “Federico Gómez” Secretaría de Salud, Dr. Márquez No. 162, Col Doctores, Alcaldía Cuauhtémoc, Ciudad de México 06720, México
9
Bioterio, Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Col Doctores, Alcaldía Cuauhtémoc, Ciudad de México 06720, México
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(18), 9876; https://doi.org/10.3390/ijms25189876
Submission received: 26 July 2024 / Revised: 4 September 2024 / Accepted: 8 September 2024 / Published: 12 September 2024

Abstract

Urinary tract infections (UTIs) represent a clinical and epidemiological problem of worldwide impact that affects the economy and the emotional state of the patient. Control of the condition is complicated due to multidrug resistance of pathogens associated with the disease. Considering the difficulty in carrying out effective treatment with antimicrobials, it is necessary to propose alternatives that improve the clinical status of the patients. With this purpose, in a previous study, the safety and immunostimulant capacity of a polyvalent lysate designated UNAM-HIMFG prepared with different bacteria isolated during a prospective study of chronic urinary tract infection (CUTI) was evaluated. In this work, using an animal model, results are presented on the immunostimulant and protective activity of the polyvalent UNAM-HIMFG lysate to define its potential use in the control and treatment of CUTI. Female Balb/c mice were infected through the urethra with Escherichia coli CFT073 (UPEC O6:K2:H1) strain; urine samples were collected before the infection and every week for up to 60 days. Once the animals were colonized, sublingual doses of UNAM-HIMFG lysate were administrated. The colonization of the bladder and kidneys was evaluated by culture, and their alterations were assessed using histopathological analysis. On the other hand, the immunostimulant activity of the compound was analyzed by qPCR of spleen mRNA. Uninfected animals receiving UNAM-HIMFG lysate and infected animals administered with the physiological saline solution were used as controls. During this study, the clinical status and evolution of the animals were evaluated. At ninety-six hours after infection, the presence of CFT073 was identified in the urine of infected animals, and then, sublingual administration of UNAM-HIMFG lysate was started every week for 60 days. The urine culture of mice treated with UNAM-HIMFG lysate showed the presence of bacteria for three weeks post-treatment; in contrast, in the untreated animals, positive cultures were observed until the 60th day of this study. The histological analysis of bladder samples from untreated animals showed the presence of chronic inflammation and bacteria in the submucosa, while tissues from mice treated with UNAM-HIMFG lysate did not show alterations. The same analysis of kidney samples of the two groups (treated and untreated) did not present alterations. Immunostimulant activity assays of UNAM-HIMFG lysate showed overexpression of TNF-α and IL-10. Results suggest that the lysate activates the expression of cytokines that inhibit the growth of inoculated bacteria and control the inflammation responsible for tissue damage. In conclusion, UNAM-HIMFG lysate is effective for the treatment and control of CUTIs without the use of antimicrobials.
Keywords: urinary tract infections; bacterial lysate; animal model; UTI treatment urinary tract infections; bacterial lysate; animal model; UTI treatment

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MDPI and ACS Style

Acevedo-Monroy, S.E.; Hernández-Chiñas, U.; Rocha-Ramírez, L.M.; Medina-Contreras, O.; López-Díaz, O.; Ahumada-Cota, R.E.; Martínez-Gómez, D.; Huerta-Yepez, S.; Tirado-Rodríguez, A.B.; Molina-López, J.; et al. UNAM-HIMFG Bacterial Lysate Activates the Immune Response and Inhibits Colonization of Bladder of Balb/c Mice Infected with the Uropathogenic CFT073 Escherichia coli Strain. Int. J. Mol. Sci. 2024, 25, 9876. https://doi.org/10.3390/ijms25189876

AMA Style

Acevedo-Monroy SE, Hernández-Chiñas U, Rocha-Ramírez LM, Medina-Contreras O, López-Díaz O, Ahumada-Cota RE, Martínez-Gómez D, Huerta-Yepez S, Tirado-Rodríguez AB, Molina-López J, et al. UNAM-HIMFG Bacterial Lysate Activates the Immune Response and Inhibits Colonization of Bladder of Balb/c Mice Infected with the Uropathogenic CFT073 Escherichia coli Strain. International Journal of Molecular Sciences. 2024; 25(18):9876. https://doi.org/10.3390/ijms25189876

Chicago/Turabian Style

Acevedo-Monroy, Salvador Eduardo, Ulises Hernández-Chiñas, Luz María Rocha-Ramírez, Oscar Medina-Contreras, Osvaldo López-Díaz, Ricardo Ernesto Ahumada-Cota, Daniel Martínez-Gómez, Sara Huerta-Yepez, Ana Belén Tirado-Rodríguez, José Molina-López, and et al. 2024. "UNAM-HIMFG Bacterial Lysate Activates the Immune Response and Inhibits Colonization of Bladder of Balb/c Mice Infected with the Uropathogenic CFT073 Escherichia coli Strain" International Journal of Molecular Sciences 25, no. 18: 9876. https://doi.org/10.3390/ijms25189876

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