Interpretation of Science papers! Changes in metabolic status actually make bacteria resistant to antibiotics

Bacteria have many ways to escape the antibiotics we use to deal with them.

Most known mutations that confer resistance occur in genes targeted by specific antibiotics.

In a new study, researchers from the Massachusetts Institute of Technology in the United States have now identified another type of mutation that helps bacteria develop resistance.

Changes in metabolic status lead to antibiotic resistance.

The corresponding author of the paper, Professor James Collins of the Massachusetts Institute of Technology's Institute of Medical Engineering and Science said, "This research provides us with new insights on how to improve the effectiveness of existing antibiotics because it emphasizes that downstream metabolism plays an important role.

Metabolic control

This new study builds on previous research in the Collins laboratory, showing that when antibiotics are used, many bacteria are forced to accelerate their metabolism, leading to the accumulation of toxic by-products.

However, although hyperactive metabolism plays a role in bacterial cell death, scientists have not found any evidence that this metabolic stress causes mutations that help bacteria evade antibiotic drugs.

First, they conducted a study similar to what is commonly used to find antibiotic resistance mutations.

Lopatkin said, “Many previous studies have focused on some evolutionary clones, or the sequencing of some genes that we expect to have mutations, because they are related to the way antibiotic drugs work.

For example, the antibiotic ciprofloxacin targets DNA gyrase, an enzyme involved in DNA replication, and forces the enzyme to destroy the cell's DNA.

In their first adaptive evolution screening, these researchers analyzed more E.

In order to screen out more mutations related to metabolism, these researchers conducted a second screening.

These researchers then sequenced the genomes of these bacteria and found some mutations related to metabolism that they saw in the first screening, as well as other mutations in metabolic genes.

New target

Subsequently, these researchers genetically modified typical E.

The researchers said these findings raise the possibility that forcing bacteria into a highly metabolic state can increase the effectiveness of existing antibiotics.

Lopatkin said, "I think these results are really exciting, because they reveal genetic targets that may improve the efficacy of antibiotics, and these targets have not yet been studied.

Reference materials:

1.
Allison J.
Lopatkin et al.
Clinically relevant mutations in core metabolic genes confer antibiotic resistance.
Science, 2021, doi:10.
1126/science.
aba0862.

2.
Mattia Zampieri.
The genetic underground of antibiotic resistance.
Science, 2021, doi:10.
1126/science.
abf7922.

3.
Metabolic mutations help bacteria resist drug treatment

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