Avec ces nanoparticules, un simple test d'urine pourrait diagnostiquer une pneumonie bactérienne: Les résultats pourraient également indiquer si les antibiotiques ont réussi à traiter l'infection

Pneumonie, a respiratory disease that kills about 50,000 people in the United States every year, can be caused by many different microbes, including bacteria and viruses. Rapid detection of pneumonia is critical for effective treatment, especially in hospital-acquired cases which are often more severe. toutefois, current diagnostic approaches often take several days to return definitive results, making it harder for doctors to prescribe the right treatment.

A strong immune response can be seen in this immunofluorescence image of lung tissue infected with pneumonia where immune cells are stained green and red. Image: Colin Buss

MIT researchers have now developed a nanoparticle-based technology that could be used to improve the speed of diagnosis. This type of sensor could also be used to monitor whether antibiotic therapy has successfully treated the infection, says Sangeeta Bhatia, le professeur John et Dorothy Wilson des sciences de la santé et de la technologie et en génie électrique et informatique et l'auteur principal de l'étude.

« Si les symptômes du patient disparaissent, alors vous assumez le médicament fonctionne. Mais si les symptômes du patient ne disparaissent pas, alors vous voulez voir si la bactérie est encore en croissance. Nous avons essayé de répondre à cette question,» Dit Bhatia, qui est également membre de l'Institut Koch pour la recherche sur le cancer intégrative et de l'Institut de génie médical et de la Science du MIT.

Graduate student Colin Buss and recent PhD recipient Jaideep Dudani are the lead authors of the paper, which appears online Nov. 29 dans la revue EBioMedicine. Reid Akana, an MIT senior, and Heather Fleming, director of research for Bhatia’s lab, are also authors of the paper.

Sensors in the body

Il y a plusieurs années, Bhatia and her colleagues developed a diagnostic approach that amplifies a signal from biomarkers already present in the body — specifically, enzymes called proteases, which chop up other proteins. The human genome encodes more than 500 different proteases, each of which targets different proteins.

The team developed nanoparticles coated with peptides (short proteins) that can be chopped up by certain proteases, such as those expressed by cancer cells. When these particles are injected into the body, they accumulate in tumors, if any are present, and proteases there chop the peptides from the nanoparticles. These peptides are eliminated as waste and can be detected by a simple urine test.

“We’ve been working on this idea that measuring enzyme activity could be a new way to peer inside the body," dit Bhatia.

In recent studies, she has shown that this approach can be used to detect different types of cancers, including very small ovarian tumors, which could enable earlier diagnosis of ovarian cancer.

For their new study, the researchers wanted to explore the possibility of diagnosing infection by detecting proteases that are produced by microbes. They began with a species of bacteria called Pseudomonas aeruginosa, which can cause pneumonia and is a particularly common cause of hospital-acquired cases. Pseudomonas expresses a protease called LasA, de sorte que les chercheurs ont conçu des nanoparticules avec des peptides qui peuvent être clivés par Lasa.

Les chercheurs ont également mis au point un second capteur à base de nanoparticules capable de surveiller la réponse immunitaire à l'infection de l'hôte. Ces nanoparticules sont recouverts de peptides qui sont clivés par un type de protéase appelée élastase, qui est produite par des cellules immunitaires appelées neutrophiles.

Chez certains patients atteints de pneumonie, even if an antibiotic clears out the bacteria causing the infection, a chest X-ray may still show inflammation because neutrophils are still active. Using these two sensors together could reveal whether an antibiotic has cleared the infection, in cases where a chest X-ray still shows inflammation after treatment.

“The sensors can help you distinguish between whether there’s an infection and inflammation, versus inflammation and no infection," dit Bhatia. “What we showed in the paper is that when you treat with the right antibiotic, the infection goes down but the inflammation persists.”

The researchers also showed that if they treated mice with an ineffective antibiotic, both bacteria levels and inflammation levels stayed high. This kind of test could help to reveal whether an antibiotic is working, in cases where a patient’s symptoms haven’t improved within a few days.

Diagnosing many infections

Pour cette étude, the researchers delivered the nanoparticles intravenously, but they are now working on a powdered version that could be inhaled.

Bhatia prévoit que cette approche pourrait être utilisée pour déterminer si un patient a une pneumonie bactérienne ou virale, ce qui aiderait les médecins à décider si le patient doit recevoir des antibiotiques ou non. Le test définitif, la croissance d'une culture bactérienne du mucus craché, prend plusieurs jours, afin que les médecins fondent leurs décisions sur les symptômes des patients et l'imagerie par rayons X - un processus qui ne peut pas toujours être précis.

Pour créer un diagnostic plus complet, Bhatia’s lab is now working on adding peptides that could interact with proteases from other types of bacteria that cause pneumonia, as well as proteases that the host immune system produces in response to either viral or bacterial infection. The researchers are also working on sensors that could easily distinguish between active and dormant forms of tuberculosis.

Bhatia and others have started a company called Glympse Bio that has licensed the protease sensing technology and is now working on developing protease sensors for possible use in humans. Next year, they plan to begin a phase I clinical trial of a sensor that can detect liver fibrosis, an accumulation of scar tissue that can lead to cirrhosis.

La source: http://news.mit.edu, par Anne Trafton