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Volume 13
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10.3390/microorganisms13112591
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

The Nucleoid-Associated Protein Fis Represses Type 3 Fimbriae to Modulate Biofilm and Adherence Formation in Klebsiella pneumoniae

by
Santa Mejia-Ventura
1,2,
Jorge Soria-Bustos
3,
Fernando Chimal-Cázares
2,
Gabriela Hernández-Martínez
2,
Roberto Rosales-Reyes
4,
Miguel A. De la Cruz
3,5,
Jorge A. Yañez-Santos
3,
Maria L. Cedillo
3,
Gonzalo Castillo-Rojas
6,
Dimitris Georgellis
7 and
Miguel A. Ares
2,8,*
1
Posgrado en Ciencias Biológicas, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
2
Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
3
Centro de Detección Biomolecular, Benemérita Universidad Autónoma de Puebla, Puebla 72592, Mexico
4
Unidad de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
5
Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Puebla 72410, Mexico
6
Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
7
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
8
Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
*
Author to whom correspondence should be addressed.
Microorganisms 2025, 13(11), 2591; https://doi.org/10.3390/microorganisms13112591 (registering DOI)
Submission received: 16 October 2025 / Revised: 7 November 2025 / Accepted: 12 November 2025 / Published: 13 November 2025
(This article belongs to the Special Issue Transcriptional Regulation in Bacteria, 2nd Edition)
Review Reports Versions Notes

Abstract

The nucleoid-associated protein Fis functions as a global regulator that influences various cellular processes in Gram-negative bacteria. In this study, we examined the role of Fis in the transcriptional regulation of type 3 fimbriae in Klebsiella pneumoniae, a notable opportunistic pathogen associated with hospital-acquired infections. Our transcriptional analyses revealed that deleting the fis gene caused a significant upregulation of mrkA and mrkH, the genes responsible for the structure and regulation of type 3 fimbriae, respectively. Additionally, phenotypic assays demonstrated that the Δfis mutant exhibited enhanced biofilm formation and greater adherence to A549 lung epithelial cells compared to the wild-type strain. These effects were restored to wild-type levels in the cis-complemented strain. Electrophoretic mobility shift assays confirmed that Fis directly binds to the regulatory regions upstream of both mrkA and mrkH, indicating that repression occurs through direct interaction with the promoter. In summary, our findings show that Fis acts as a transcriptional repressor of mrkA and mrkH, thereby negatively regulating the expression of type 3 fimbriae, biofilm formation, and adherence. This study highlights Fis as a direct regulator of fimbrial expression and biofilm development in K. pneumoniae, deepening our understanding of its virulence regulatory network.
Keywords: Klebsiella pneumoniae; Fis; type 3 fimbriae; mrkA; mrkH; biofilm; adherence Klebsiella pneumoniae; Fis; type 3 fimbriae; mrkA; mrkH; biofilm; adherence

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MDPI and ACS Style

Mejia-Ventura, S.; Soria-Bustos, J.; Chimal-Cázares, F.; Hernández-Martínez, G.; Rosales-Reyes, R.; De la Cruz, M.A.; Yañez-Santos, J.A.; Cedillo, M.L.; Castillo-Rojas, G.; Georgellis, D.; et al. The Nucleoid-Associated Protein Fis Represses Type 3 Fimbriae to Modulate Biofilm and Adherence Formation in Klebsiella pneumoniae. Microorganisms 2025, 13, 2591. https://doi.org/10.3390/microorganisms13112591

AMA Style

Mejia-Ventura S, Soria-Bustos J, Chimal-Cázares F, Hernández-Martínez G, Rosales-Reyes R, De la Cruz MA, Yañez-Santos JA, Cedillo ML, Castillo-Rojas G, Georgellis D, et al. The Nucleoid-Associated Protein Fis Represses Type 3 Fimbriae to Modulate Biofilm and Adherence Formation in Klebsiella pneumoniae. Microorganisms. 2025; 13(11):2591. https://doi.org/10.3390/microorganisms13112591

Chicago/Turabian Style

Mejia-Ventura, Santa, Jorge Soria-Bustos, Fernando Chimal-Cázares, Gabriela Hernández-Martínez, Roberto Rosales-Reyes, Miguel A. De la Cruz, Jorge A. Yañez-Santos, Maria L. Cedillo, Gonzalo Castillo-Rojas, Dimitris Georgellis, and et al. 2025. "The Nucleoid-Associated Protein Fis Represses Type 3 Fimbriae to Modulate Biofilm and Adherence Formation in Klebsiella pneumoniae" Microorganisms 13, no. 11: 2591. https://doi.org/10.3390/microorganisms13112591

APA Style

Mejia-Ventura, S., Soria-Bustos, J., Chimal-Cázares, F., Hernández-Martínez, G., Rosales-Reyes, R., De la Cruz, M. A., Yañez-Santos, J. A., Cedillo, M. L., Castillo-Rojas, G., Georgellis, D., & Ares, M. A. (2025). The Nucleoid-Associated Protein Fis Represses Type 3 Fimbriae to Modulate Biofilm and Adherence Formation in Klebsiella pneumoniae. Microorganisms, 13(11), 2591. https://doi.org/10.3390/microorganisms13112591

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