抗生素,细菌基因组 z-bo 2020-09-24 407

　　Most antibiotics currently used are actually natural molecules produced by bacteria. Due to the increasing resistance of bacteria, there is an urgent need to develop new antibiotics in medicine. However, inducing bacteria to produce new antibiotics is a tricky business. Most bacteria do not grow in the laboratory. Even if these bacteria are grown in the laboratory, most antibiotic-producing genes are rarely expressed. Recently, researchers at Rockefeller University have found a new way to solve the problem.

　　Researchers discover new antibiotics Humimycin A and Humimycin B that kill drug-resistant Staphylococcus aureus

　　Researchers found the bacterial genome in the human body from public genetic databases, and then used specialized computer software to scan hundreds of gene clusters specifically compiled to synthesize non-ribosomal peptide molecules. These non-ribosomal peptides are the basis of many antibiotics. Finally, they used software to predict the molecular chemical structure of the gene cluster. By using computational methods to select genes that produce antibiotic compounds in the microbial genome, and then skip the bacterial culture process and directly synthesize these compounds themselves. Using this type of method, they have successfully found two new antibiotics.

　　trip to discover huminmycin

　　From the 57 potentially useful gene clusters initially identified by the software, the researchers further screened out 30 gene clusters. Brandi and his colleagues then used a solid-phase peptide synthesis method to create 25 different compounds.

　　By testing the response of these compounds to human pathogens, the researchers successfully screened out two antibiotics, which they named Humimycin A and Humimycin B. Both are found in a type of bacteria called Rhodococcus, which is a new antibiotic never found in traditional bacterial culture.

　　Staphylococcus and Streptococcus are the two most harmful bacteria to the human body. In recent years, they have gradually shown resistance to various antibiotics. Experiments showed that humimycins cut off the cell wall synthesis pathway by inhibiting bacterial cell wall synthetase, and the bacteria died immediately. Therefore, humimycins are very effective against these two types of bacteria.

　　Humimycins does more than that. Beta-lactam is a widely used prescription antibiotic, and its effect often disappears as the bacteria become resistant. However, scientists discovered that one of the humimycins can be used to resensitize bacteria and eliminate the bacteria's resistance to β-lactam.

　　magical synergy

　　In the experiment, they exposed β-lactam-resistant staphylococci to a mixture of β-lactam antibiotics and humimycin A and found that the bacteria died immediately. Even when the Humimycin A content is small, the same result still appears. So Brandi guessed that both antibiotics played a role in interrupting bacterial life activities.

　　To further verify the inference, Brandi and his colleagues infected mice with β-lactam-resistant Staphylococcus aureus. They found that the effect of mice treated with a mixture containing humimycin A and β-lactam antibiotics was far better than that of mice treated with only one of these drugs. This provides a new idea for people to treat drug-resistant Staphylococcus aureus.

　　Brandi hopes that this discovery will inspire more scientific research teams to explore the bacterial genome and find more new antibiotics. In addition, Brandi suggests that everyone's vision should not be limited to the human microbial genome, which is a huge treasure, waiting for humans to mine.