Science Advances: The deadly second only to COVID-19!

With the spread of the new coronavirus around the world, "pneumonia", a common infectious disease of the respiratory system, has once again attracted people's attention.
However, in fact, before the COVID-19 pandemic, pneumonia infection was the cause of global pneumonia deaths.
The main reason
.

Streptococcus pneumoniae was first isolated from the sputum of patients in France and the United States by Louis Pasteur and GM Sternberg in 1881.
Like COVID-19, the Streptococcus pneumoniae virus can also be used when we cough or sneeze.
Droplet spread, mainly infecting children and the elderly
.

It can cause deadly bacterial pneumonia, meningitis, sepsis, otitis media, and sinusitis

Recently, a scientific research team led by the University of Melbourne published an article entitled The structural basis of bacterial manganese import in Science Advances .
The study found a new way to fight pneumonia by "starving to death" pathogens!

Science Advances Science Advances The structural basis of bacterial manganese import The structural basis of bacterial manganese import

As we all know, trace elements and minerals are very important to maintain the health of the body.
Among them, the content of only 12-20 mg of "manganese (Mn)" in the human body is closely related to the human body.
It mainly participates in the structure or structure of enzymes in the body.
Activate enzymes to play a physiological role
.

What is shocking is that in 2010, scientists from the Doherty Institute discovered that the mineral "manganese" is not only a talisman to ensure the normal operation of the body, but also vital to the survival, metabolism and infectivity of the bacteria "Streptococcus pneumoniae" in the human body
.

A year later, researchers from the University of Adelaide, Australia, published a study in the international journal Nature Chemical Biology once again to prove the authenticity of this new discovery.

After determining that “manganese” is an essential mineral for the survival of pathogens, scientists began to search for the carrier and entrance of “manganese” into Streptococcus pneumoniae.
The charge in the lipid bilayer is shielded to achieve transmembrane translocation.
Once the protein is destroyed and nutrients cannot be transported to the body of the pathogen, Streptococcus pneumoniae will be "starved"
.

Therefore, in order to determine the structure and working principle of this transporter, and develop new drugs and treatments for Streptococcus pneumoniae, the researchers determined how the three-dimensional structure of the transporter works based on X-Ray Crystallography
.

Structure and activity of transporter

The structure and activity of the transporter The structure and activity of the transporter

However, it should be noted that the prerequisite for using this technology is to cultivate protein crystals in vitro.
However, because the cell membrane is a barrier for communication between the inside of the cell and the outside world, it is composed of fat or lipid molecules, and the transporter is tightly embedded in the cell membrane.
In bacterial cell membranes, it is very difficult to extract transporters from Streptococcus pneumoniae
.

In order to solve this problem, the researchers used a kind of "detergent" to elute the transporter from the membrane.
After analyzing its structure, they found that the transporter belongs to the ancient and huge "ABC superfamily".
The family is a group of transmembrane proteins, a unidirectional substrate transport pump with an ATP binding region, which completes the transmembrane transport of multiple molecules in an active transport mode
.

However, the transporter eluted from Streptococcus pneumoniae is smaller and more compact than other family members, and has a unique "manganese" pathway, which is responsible for transportation and signal transduction.

Manganese translocation pathway

Manganese translocation pathwayManganese translocation pathway

Therefore, finding a way to block the nutrient transport of the pathogen and prevent the transporter from bringing "manganese" into the pathogen is one of the means to develop new therapies for the treatment and prevention of lung cancer
.

The author of the study, Professor Hugo MacDermott-Opeskin, said: "The current drugs for pneumonia kill Streptococcus pneumoniae mainly by destroying the complete structure of the bacterial cell wall.

All in all, "starving" Streptococcus pneumoniae will be a brand new way to treat pneumonia, and a brand new breakthrough to solve the problem of antibiotic resistance! At the same time, this research has also caused us to ponder whether this method of "starving" Streptococcus pneumoniae can be applied to COVID-19?

Original source:

Original source:

Stephanie L.

The structural basis of bacterial manganese import.
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