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A new antibiotic
that can fight resistant bacteria.
that can fight resistant bacteria.
Antibiotics have long been considered miraculous in
treating bacterial infections.
However, over time, many pathogens have evolved to be resistant to antibiotics, so the search for new drugs has become even more urgent
.
The researchers from the University of Basel are part of an international team that uses computational analysis to identify a new antibiotic and decipher its mode of
action.
Their research is an important step in
the development of new and powerful drugs.
The World Health Organization calls the steady increase in the number of bacteria resistant to antibiotics a "silent pandemic.
"
This situation is made worse
by the fact that not many new drugs have entered the market in recent decades.
Even now, not all infections are treated appropriately, and patients are still at risk
of harm from routine interventions.
New active substances are urgently needed to stop the spread
of antibiotic-resistant bacteria.
Recently, a team led by researchers at Northeastern University in Boston and Professor Sebastian Hiller from the University of Basel's Center for Biology made a major discovery
.
The study is part of the National Research Competence Center's (NCCR) "Antimicrobial" program, and its results were recently published in the journal Nature Microbiology
.
The researchers discovered the new antibiotic, Dynobactin
, through a computational screening method.
This compound kills gram-negative bacteria, including many dangerous and drug-resistant pathogens
.
Hiller said: "Antibiotic research against this type of bacteria is no small matter
.
They are well protected by a double membrane, so there is little chance of
attack.
Over millions of years of evolution, these bacteria have found many ways to make antibiotics harmless
.
”
Just last year, Hiller's team deciphered the mode
of action of the recently discovered peptide antibiotic Darobactin.
The knowledge gained is integrated into the screening process
for new compounds.
The researchers took advantage of the fact that
many bacteria produce antibiotic peptides to fight each other.
These peptides, unlike natural substances, are encoded in the bacterial genome
.
"The genes of this peptide antibiotic share a common characteristic," explains
co-first author Dr.
Seyed M.
Modaresi.
Based on this feature, the computer systematically screened the entire genome
of the bacteria that produced the peptide.
That's how we identify Dynobactin
.
"In their study, the authors have shown that this new compound is very effective
.
Mice with life-threatening sepsis caused by drug-resistant bacteria survived severe infections by administering Dynobactin
.
By combining different methods, researchers have been able to address the structure and mechanism
of action of Dynobactin.
The peptide blocks the bacterial membrane protein BamA, which plays an important role
in the formation and maintenance of bacterial outer protective membranes.
"Dynobactin plugs into BamA from the outside like a plug, preventing it from working
.
So, the bacteria die," Modaresi said
.
"Although Dynobactin bears little chemical resemblance to known Darobactin, it has the same target on the surface of bacteria
.
This is something we didn't expect at first
.
”
At the molecular level, however, the scientists found that Dynobactin interacts differently with BamA than Darobactin
.
By combining certain chemical characteristics of the two, potential drugs
can be further refined and optimized.
This is an important step
in the development of effective drugs.
Hiller said: "Computer-based screening will provide a new boost
to identifying much-needed antibiotics.
In the future, we hope to expand our search and investigate more peptides on their suitability as antimicrobials
.
”
Reference:
