Caldas Ferraz, L. F. | Search bioRxiv

bioRxiv2025

Protection Against Pneumonia Induced By Vaccination With Fimbriae Subunits From Klebsiella pneumoniae

Klebsiella pneumoniae infections pose a great burden worldwide, causing high morbidity and mortality, which are worsened by the increase in multidrug resistant strains. New therapeutic/prophylactic strategies are urgently needed to overcome antibiotic resistance and reduce the health and economic impacts of diseases caused by this pathogen. Fimbriae are important virulence factors involved in biofilm formation and adhesion to host cells. Their exposed location, conservation among clinical isolates and adjuvant properties make them interesting candidates for inclusion in protein-based vaccines. Therefore, the present work investigated the immunological potential of type 1 and 3 fimbriae subunits in a murine model of K. pneumoniae lung infection. Subcutaneous immunization with recombinant FimA and MrkA induced high IgG1 production; the antibodies efficiently recognized the native proteins at the bacterial surface, promoted C3 deposition and reduced biofilm formation by K. pneumoniae in vitro. Mice vaccinated with the co-administered proteins reduced the bacterial loads in the lungs after intranasal challenge, less inflammation and tissue damage. The results suggest that both type 1 and type 3 fimbriae contribute to protection against K. pneumoniae lung infection, inducing antibodies that bind to the bacteria and favor complement deposition and clearance by the host, while inhibiting biofilm formation.

immunology↗

bioRxiv2020

Functional insights from KpfR, a new transcriptional regulator of fimbrial expression that is crucial for Klebsiella pneumoniae pathogenicity

Although originally known as an opportunistic pathogen, Klebsiella pneumoniae has been considered a worldwide health threat nowadays due to the emergence of hypervirulent and antibiotic-resistant strains capable of causing severe infections not only on immunocompromised patients but also on healthy individuals. Fimbriae is an essential virulence factor for K. pneumoniae, especially in urinary tract infections, because it allows the pathogen to adhere and invade urothelial cells and to form biofilms on biotic and abiotic surfaces. The importance of fimbriae for K. pneumoniae pathogenicity is highlighted by the large number of fimbrial gene clusters on the bacterium genome, which requires a coordinated and finely adjusted system to control the synthesis of these structures. In this work, we describe KpfR as a new transcriptional repressor of fimbrial expression in K. pneumoniae and discuss its role in the bacterium pathogenicity. K. pneumoniae lacking the kpfR gene exhibited a hyperfimbriated phenotype with enhanced biofilm formation and greater adhesion to and replication within epithelial host cells. However, the mutant strain was attenuated for colonization of the bladder in a murine model of urinary tract infection. These results indicate that KpfR is an important transcriptional repressor that, by negatively controlling the expression of fimbriae, prevents K. pneumoniae from having a hyperfimbriated phenotype and from being recognized and eliminated by the host immune system. IMPORTANCEFimbriae are crucial virulence factor for many pathogens because they allow the pathogen to adhere and invade host cells and to form biofilm on biotic and abiotic surfaces. However, the synthesis of fimbriae requires a precise and coordinated control to guarantees the production of these structures only when necessary, thus avoiding unnecessary energy expenditure and bacterial clearance by the host immune cells. Herein, we describe for the first time the role of the transcriptional repressor of fimbrial expression KpfR on the pathogenicity of K. pneumoniae, a Gram-negative pathogen that has gained worldwide attention, notably for being the causative agent of severe and metastatic infections even on healthy individuals. By deleting the kpfR gene, we show that the mutant strain loses the control of fimbriae production, resulting in a hyperfimbriated phenotype that impairs K. pneumoniae ability to colonize a murine model of urinary tract infection.

microbiology↗