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Article source: Medical Rubik's Cube Pro
Antibiotic resistance remains one of the biggest public health challenges
Scientists at the New York University School of Medicine are exploring different strategies.
When exposed to antibiotics, some bacteria enter a dormant state to survive the process mediated by the production of hydrogen sulfide molecules (H2S)
In this study, the scientists first used mutations of Staphylococcus aureus and Pseudomonas aeruginosa to prove that CSE is an important source of H2S
Figure 1 | Bacterial CSE is the main source of H2S in Staphylococcus aureus and Pseudomonas aeruginosa
Scientists believe that CSE can be used as a target for drugs designed to make bacteria susceptible to antibiotics
After identifying a possible bacterial CSE site that can be combined with drugs without causing toxic side effects, the research team screened approximately 3.
In the laboratory petri dishes, these three drugs have a strong inhibitory effect on the production of H2S by Staphylococcus aureus and Pseudomonas aeruginosa, and improve the efficacy of different kinds of antibiotics
The chemical structure of bacterial CSE inhibitor, human CSE inhibitor (PAG) and negative control (NL1F3)
Next, the scientists further tested NL1 in two mouse models of infection
In the mouse model of Staphylococcus aureus sepsis, combining NL1 and gentamicin helped 50% of the mice survive, while 90% of the mice in the control group died
Bacterial CSE inhibition and gentamicin have a synergistic effect in mouse infection models
Further analysis showed that NL1 can inhibit the tolerance of bacteria, destroy the formation of biofilms, and significantly reduce the number of resident bacteria (which can stop reproduction and reduce energy consumption to survive under antibiotic treatment), reaching the level of CSE gene inactivation A similar level of effect
CSE inhibits the formation of destroying bacterial biofilms and significantly reduces lingering bacteria
So far, most of the research on the problem of antibiotic resistance has focused on the development of new antibiotics
A team led by scientists at the University of California, Los Angeles (UCLA) recently took inspiration from the proteins produced by Pseudomonas aeruginosa that kill competing bacteria, and they are designing new antibiotics based on these proteins called R-type pyocins
The New York University scientists who led the study believe that inhibiting the bacterial H2S by inhibiting CSE may be a new way to enhance the effectiveness of existing antibiotics
.
Note: The original text has been deleted
Reference materials:
1# Making drug-resistant bacteria susceptible to antibiotics (Source: FIERCE Biotech)
2# Konstantin Shatalin et al.
Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance.
Science (2021)