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A bacterial spray to keep respiratory infections away?

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A new study found that harmless bacteria that live in our upper respiratory tract inhibit the growth of Streptococcus pneumoniae, a leading cause of respiratory infections. The study opens a possibility for probiotic-based therapies, such as nasal sprays, with the potential to reduce colonization by this pathogen.

Streptococcus pneumoniae, or pneumococcus, causes a range of infections, from ear infections and sinusitis to more severe diseases such as meningitis, sepsis, and pneumonia. Children, the elderly and immunocompromised patients are the most vulnerable to these infections. Each year, around 300 thousand children around the world lose their lives due to this pathogen.

Currently, there are more than 100 different recognized strains of S. pneumoniae and no vaccine can protect against them all. Moreover, some of these bacteria are already resistant to antibiotics. Now, a new study published in the Applied and Environmental Microbiology journal, by the American Society for Microbiology, reveals that some bacteria in the nasopharynx and oropharynx – the regions located right behind the nasal cavity and the mouth, respectively, – can inhibit most S. pneumoniae strains.

“When studying the frequency of colonization by S. pneumoniae we noticed that some people who were not colonized by this pathogen were still colonized by other harmless bacteria, particularly Streptococcus oralis and Streptococcus mitis”, explains Raquel Sá-Leão, leader of the Molecular Microbiology of Human Pathogens laboratory at ITQB NOVA, who led this study. This led the researchers to question if other residing microbes play a role in limiting S. pneumoniae’s presence in the upper respiratory tract.

To explore this possibility, the research team screened a collection of strains collected from nasopharyngeal swabs of 300 children and adults who were not colonized with S. pneumoniae for their ability to inhibit this pathogen. “From this extensive collection, we identified seven strains of S. oralis and six S. mitis with strong inhibitory activity against S. pneumoniae”, reveals Sara Handem, ITQB NOVA researcher and one of the authors of the paper. "These bacteria can even prevent the formation of pneumococcal biofilms - groups of bacteria that attach to the respiratory mucosa, forming a community that is more resilient to the immune system and antibiotics" she adds.

The anti-pneumococcal activity of S. oralis and S. mitis strains depends heavily on the production of small antimicrobial molecules called bacteriocins. “In addition to acting against most variants of pneumococci, bacteriocins are expected to induce less resistance than antibiotics and to be more specific, acting against pneumococci but preserving the rest of the microbiota,” explains João Lança, also an author of the study and a researcher at ITQB NOVA.

“Our study presents a promising complementary or standalone strategy to reduce the pneumococcal disease burden. This strategy aligns with the World Health Organization’s recommendations to target colonization as a fundamental key step to prevent disease and transmission of pneumococci”, Carina Valente, ITQB NOVA researcher and study co-author adds. The team has already filled a provisional patent application that covers pharmaceutical compositions comprising these bacteria and their pneumococcus-inhibiting molecules (PT119647).

The next steps will be to explore the mechanism of action of bacteriocins and to evaluate the efficacy and safety of these and the microbes that produce them, using in vivo models. “We envision that our results could lead to novel probiotic formulations, such as nasal sprays”, concludes João Borralho, ITQB NOVA researcher and co-author of the paper.

This work was developed in collaboration with ITQB NOVA’s Microbial Development Laboratory, led by Adriano O. Henriques, and the Carnegie Mellon University (USA).

ITQB NOVA researchers (from the left to the right) João Lança, Carina Valente, Raquel Sá-Leão and João Borralho.

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