Antibiotic arenicin found effective against M. abscessus in cell study
Antibiotic also active against Pseudomonas aeruginosa, Candida albicans
The antibiotic arenicin may be effective at killing resistant Mycobacterium abscessus, a type of bacteria that can cause serious infections in people with cystic fibrosis (CF), according to a study in cells.
Given alone or in combination with conventional antibiotics, arenicin is also active against other bacteria or fungi that often infect people with CF, such as Pseudomonas aeruginosa or Candida albicans, opening new perspectives for treatment.
The study, “Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus,” was published in the Journal of Biomedical Science by researchers in France.
People with CF are more likely to get lung infections because they produce an abnormally thick and sticky mucus that can trap bacteria and other germs in their airways, making it harder for the body to clear them out.
A type of rapidly growing bacteria called M. abscessus can cause serious lung infections in people with CF. Because they are naturally resistant to many of the conventional antibiotics, treatment may require a combination of antibiotics for a prolonged period.
Arenicin’s effect on M. abscessus
Antimicrobial peptides — short molecules of no more than 100 protein building blocks — are less likely to cause resistance and may offer “a good alternative to conventional antibiotics,” wrote the researchers, who tested how well arenicin works against M. abscessus.
Arenicin is produced naturally by lugworms to defend against bacteria. There are three known forms — Ar-1, Ar-2, and Ar-3. All three were found to outperform amikacin, considered one of the most effective antibiotics against M. abscessus.
The three forms of arenicin were effective at killing both the smooth (S) and rough (R) variants of M. abscessus. Ar-2 and Ar-3 weren’t as effective against the R variant as they were against the S variant, suggesting Ar-1 may be best.
Indeed, Ar-1 was the safest form of arenicin. It didn’t cause red blood cells to break down and wasn’t toxic against lab-grown human lung, liver, or kidney cells, leading researchers to select it “for further investigations.”
Ar-1 was able to get into the bacterial membrane quickly, causing it to break down. It made both the S and R variants permeable, and didn’t cause the bacteria to become resistant to it with a 42-day exposure.
Under the microscope, Ar-1-treated bacteria looked different from untreated bacteria. “Indeed, bacteria incubated with Ar-1, especially when they are in clusters, seem to be covered by a sticky substance,” the researchers wrote.
While untreated bacteria had a smooth, intact border, bacteria treated with Ar-1 had a potholed border, “strengthening the appearance of empty cells,” wrote the researchers, who said Ar-1 may work by opening pores in the bacteria.
The scientists also made versions of the three forms of arenicin in the lab by replacing some of their cysteines, a type of building block that helps proteins keep their shape. Cysteines are important for arenicin to fold correctly and act against bacteria, the researchers found.
Antimicrobial peptides “are making a comeback,” the researchers wrote, adding that some molecules similar to arenicin are under preclinical testing for a number of bacterial infections. “Future studies should however be conducted, notably in vivo studies [in living animals], to confirm the interest of this [Ar-1] peptide in the therapeutic arsenal against bacterial infections in CF patients.”
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