NOV 19, 2016 1:28 PM PST

Analysis of Human Microbiome Yields Potential new Antibiotics

WRITTEN BY: Carmen Leitch
Rising antibiotic resistance is considered a major public health threat; one that the United Nations has taken notice of, prompting warnings about the danger it poses. Utilizing computational power, researchers looked to bacteria to find candidate compounds they were then able to synthesize. Two potential new antibiotics have been produced using this strategy.
 

 
A research team at Rockefeller University led by Sean Brady, head of the Laboratory of Genetically Encoded Small Molecules, interrogated public databases containing the genomes of bacteria that live in the human body. They wanted to find clusters of genes that were predicted to produce molecules, non-ribosomal peptides, which are the basis of myriad antibiotics.
 
There are genes within the genome of a microbe that are antimicrobial, but using bacteria to produce those compounds is fraught with challenges. Many bacterial strains are difficult to grow in a lab. Scientists would also have to determine how to manipulate the proper genes of a bacterium to make them express the antimicrobial molecules. Using computational methods avoided those problems.
 
In doing so, the team found 57 candidate gene clusters, from which 30 were chosen. Using a technique called solid-phase synthesis, 25 compounds were produced. Those compounds were then tested with human pathogens, enabling the investigators to identify the two antibiotics the scientists named humimycin A and humimycin B. The findings were published in Nature Chemical Biology.
 
The researchers placed tiny droplets of 25 newly discovered antibiotics on a carpet of beta-lactam resistant S. aureus. They identified two compounds that generated circles of dead bacteria (dark spots) around each droplet. / Credit: Sean Brady
 
Humimycin A and B are closely related and from a family of bacteria named Rhodococcus, which have not previously yielded anything resembling the humimycins when grown with typical laboratory protocols. The humimyics proved very effective combating Staphylococcus and Streptococcus bacteria, microbes that can result in serious infections in humans and tend to become antibiotic resistant.
 
Experiments determined that the humimycins act to inhibit an enzyme that aids in buildings cell walls in bacteria; without that cell-wall-building power, the bacteria die. Beta-lactams are a commonly used class of antibiotics that have a diminishing effect as bacteria build resistance to them. The researchers found, however, that humimycins can actually re-sensitize bacteria to the action of beta-lactams they had become resistant to.
 
Staphylococcus microbes that were resistant to beta-lactam died after being exposed to a beta-lactam antibiotic in combination with humimycin A. Incredibly, that effects was still seen even if there had been little effect from using humimycin A by itself. Brady suggested that is because both compounds work by disrupting different parts of the same biological pathway.
 
"It's like taking a hose and pinching it in two spots," he says. Even if neither kink halts the flow altogether on its own, "eventually, no more water comes through."
 
The scientists went a step further and used a common cause of antibiotic-resistant infections, Staphylococcus aureus, to infect mice. After being dosed with the strain, which was beta-lactam resistant, the mice were treated with a either humimycin A, a beta-lactam antibiotic, or a combination of both. The mice treated with both drugs had the best outcome, and that discovery could pave the way toward therapeutics for human use.
 
Brady is hopeful that this work will inspire others to pursue a similar line of reasoning to find other potential therapies. He plans to apply the strategy to bacterial species outside of the human microbiome, and eventually, even to those bacterial species whose genomes have not yet been sequenced.
 
Sources: Pharmacy & TherapeuticsUnited Nations, AAAS/Eurekalert! via The Rockefeller University, Nature Chemical Biology
 
About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
AUG 14, 2020
Cell & Molecular Biology
A Proposal: COVID-19 is so Deadly Because it Absorbs microRNAs
AUG 14, 2020
A Proposal: COVID-19 is so Deadly Because it Absorbs microRNAs
There are several coronaviruses that we know about, and they cause a wide range of illnesses. Some, like SARS-CoV-2, are ...
AUG 23, 2020
Microbiology
How Microbes Can Help Clean a Toxic River
AUG 23, 2020
How Microbes Can Help Clean a Toxic River
Some places in the United States have become dangerously polluted with hazardous waste. The EPA oversees a program that ...
AUG 28, 2020
Microbiology
As Buildings Reopen After Lockdowns, They Find Legionella
AUG 28, 2020
As Buildings Reopen After Lockdowns, They Find Legionella
Several schools and even buildings at the Centers for Disease Control and Prevention (CDC) have identified Legionella ba ...
SEP 07, 2020
Microbiology
How THC Can Help Relieve a Respiratory Disorder
SEP 07, 2020
How THC Can Help Relieve a Respiratory Disorder
Acute respiratory distress syndrome (ARDS) occurs when fluid builds up in the sacs in the lungs that hold air, and the l ...
SEP 28, 2020
Microbiology
The Flu Vaccine Will Not Increase the Risk of COVID-19
SEP 28, 2020
The Flu Vaccine Will Not Increase the Risk of COVID-19
Scientists and clinicians want people to get their flu shots this year, especially because of the ongoing pandemic.
NOV 17, 2020
Immunology
6 Injections a Year Prevent HIV Infections
NOV 17, 2020
6 Injections a Year Prevent HIV Infections
Last year, around 1.7 million people became infected with HIV, with around half of these being women. Encouraging result ...
Loading Comments...