Role of cathepsin B of Naegleria fowleri during primary amebic meningoencephalitis

Abstract

Naegleria fowleri causes primary amoebic meningoencephalitis in humans and experimental animals. It has been suggested that cysteine proteases of parasites play key roles in metabolism, nutrient uptake, host tissue invasion, and immune evasion. The aim of this work was to evaluate the presence, expression, and role of cathepsin B from N. fowleri in vitro and during PAM. Rabbit-specific polyclonal antibodies against cathepsin B were obtained from rabbit immunization with a synthetic peptide obtained by bioinformatic design. In addition, a probe was designed from mRNA for N. fowleri cathepsin B. Both protein and messenger were detected in fixed trophozoites, trophozoites interacted with polymorphonuclear and histological sections of infected mice. The main cathepsin B distribution was observed in cytoplasm or membrane mainly pseudopods and food-cups while messenger was in nucleus and cytoplasm. Surprisingly, both the messenger and enzyme were observed in extracellular medium. To determine cathepsin B release, we used trophozoites supernatant recovered from nasal passages or brain of infected mice. We observed the highest release in supernatant from recovered brain amoebae, and when we analyzed molecular weight of secreted proteins by immunoblot, we found 30 and 37 kDa bands which were highly immunogenic. Finally, role of cathepsin B during N. fowleri infection was determined; we preincubated trophozoites with E-64, pHMB or antibodies with which we obtained 60%, 100%, and 60% of survival, respectively, in infected mice. These results suggest that cathepsin B plays a role during pathogenesis caused by N. fowleri mainly in adhesion and contributes to nervous tissue damage.

Development and immunological evaluation of an mRNA-based vaccine targeting Naegleria fowleri for the treatment of primary amoebic meningoencephalitis

“…Moreover, the potential therapeutic efficacy of cathepsin B as a target is promising. The enhancement of survival rates in mice infected with N. fowleri through the inhibition of cathepsin B 17 underscores the importance of this enzyme in N. fowleri infections. It highlights its potential as a viable target for developing therapeutic interventions.…”

Exploring therapeutic approaches against Naegleria fowleri infections through the COVID box

“…These injuries result from the release of cysteine proteases by the amoeba, causing irreversible damage ( Lee et al, 2014 ; Serrano-Luna et al, 2007 ). These proteases play essential roles in either invading host tissues or evading the immune system, thus promoting the disease's progression ( Rodríguez-Mera et al, 2022 ). Therefore, leading to the onset of symptoms.…”