21 June 2022

Find the culprit

Nanoparticles distinguish bacterial pneumonia from viral pneumonia

Kirill Stasevich, "Science and Life"

Pneumonia, or pneumonia, is a disease with a certain set of symptoms, but these symptoms can occur due to different infections. Most often, pneumonia occurs due to bacteria or viruses, although there are fungal pneumonia, and pneumonia caused by roundworms, toxoplasmas or a malaria parasite, there are even non-infectious pneumonia. But in most cases, we repeat, the cause is bacteria or viruses, and both can also be different.

Depending on whether pneumonia has started because of a virus or because of a bacterium, you need to choose one or another method of treatment. Antibiotics are usually used against bacteria. Antibiotics do not work against viruses (although there are some exceptions), and in the case of a viral infection, you need to think about how to stimulate the antiviral response in the immune system — and so that the immune system does not destroy the lungs themselves. Of course, there have long been methods that allow us to see both bacteria and viruses in biological medical samples. But in the same sample there may be both a bacterium capable of causing pneumonia and a virus capable of causing pneumonia, and which of them is the specific cause then? For example, Streptococcus pneumoniae pneumococcus can safely inhabit the respiratory tract without disturbing in any way, but then suddenly pneumonia begins in a person, and pneumococcus and rhinovirus are seen in the analysis. Maybe it was the rhinovirus that started everything, or maybe something happened to the bacterium, maybe the antibacterial immunity weakened, and the bacterium began to actively multiply and harm our cells.

In general, we need a reliable method that would allow us to distinguish viral pneumonia from bacterial, and even better — to determine the type of bacteria and virus. Sangeeta N. Bhatia and her colleagues from the Massachusetts Institute of Technology suggest using a set of nanoparticles coated with special peptides for this. Peptides on nanoparticles do not bind to bacteria and viruses — they bind to enzymes, the level of which increases during infection. The immune system reacts differently depending on who it has to fight, viruses or bacteria. In various immune cells, certain genes are activated, and among them are the genes of proteases — enzymes that break down proteins. In respiratory infections, depending on the type of infection, the immune system operates with a set of 39 proteases. There are more of them, and if you know which of the thirty-nine proteases are particularly active now, you can find out who the immune system is fighting against.

An article in PNAS (Anahtar et al., Host protease activity classifications pneumonia etiology) describes twenty types of nanoparticles with peptides that proteases should cleave. Different proteases work differently, respectively, and peptides on nanoparticles are also different. Molecules are attached to peptides, which are sent to float freely if the peptide is cleaved by a protease. These molecules quickly end up in the urine, where they are easy to analyze.

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Experiments were conducted with mice infected with one of three pneumonia bacteria or one of two pneumonia viruses. Animals were injected into the trachea with a set of twenty nanoparticles, then urine was taken from them for analysis, and a special algorithm calculated the level of signaling molecules, determining which pathogen caused pneumonia. The entire analysis took two hours and allowed us to accurately distinguish viral pneumonia from bacterial.

As for identifying a specific bacterium or virus, then the results were no longer very accurate, but the authors of the work claim that the method can be improved. And if we talk about clinical prospects, then for a person the whole procedure can be simplified so that nanoparticles can simply be inhaled from an inhaler, and exhaled air can be used for analysis, as is done in rapid alcohol tests.

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