One study found that higher doses of antibiotics were needed to eliminate bacterial infections of the airways when other microbes were present. It helps explain why people with lung diseases such as cystic fibrosis continue to develop respiratory infections despite treatment.
In this study, published today in ISME Magazinethe researchers say that even low levels of one microbe in the airways can have profound effects on how other microbes respond to antibiotics.
The results underscore the need to consider interactions between different species of microorganisms when treating infections with antibiotics, and adjust doses accordingly.
“People with chronic infections are often infected with several pathogens at the same time, but the problem is that we don’t take this into account when deciding how many specific antibiotics to treat them with. Our results may help explain why, in these people, antibiotics do not It’s not working as it should,” said Thomas O’Brien, a PhD student at the University of Cambridge’s Department of Biochemistry and co-first author of the paper.
Chronic bacterial infections, such as respiratory infections in humans, are difficult to cure with antibiotics. Although these types of infections are often associated with a single pathogenic species, the site of infection is often co-colonized by many other microorganisms, most of which are not usually pathogenic themselves.
Treatment options often revolve around targeting pathogens, with little consideration for cohabiting species. However, these treatments often fail to resolve the infection. Until now, scientists have not had a deep understanding of why this is the case.
To obtain their results, the team developed a simplified model of the human respiratory tract containing artificial phlegm (“phlegm”), chemically similar to real phlegm coughed up during an infection, and filled with bacteria.
The model allowed them to grow mixtures of different microorganisms, including pathogens, in a stable manner for weeks at a time. This is novel because often one pathogen can quickly outgrow other pathogens and disrupt experiments. It enables researchers to replicate and study infections with multiple microorganisms in the laboratory, known as “polymicrobial infections.”
The three microorganisms used in the experiments are bacteria Pseudomonas aeruginosa and Staphylococcus aureus, and fungi Candida albicans – A combination commonly found in the airways of cystic fibrosis patients.
The researchers treated the microbial cocktail with an antibiotic called colistin, which is very effective at killing bacteria Pseudomonas aeruginosa. But when other pathogens appear at the same time Pseudomonas aeruginosa, Antibiotics didn’t help.
“We were surprised to find that an antibiotic we knew could clear the infection Pseudomonas When there are other errors, it really just doesn’t work in our laboratory model,” said Wendy Figueroa-Chavez from the University of Cambridge’s Department of Biochemistry, co-first author of the paper.
When the microbial mixture was treated with fusidic acid, a Staphylococcus aureus, and fluconazole, a specific Candida albicans.
The researchers found that significantly higher doses of each antibiotic were required to kill the bacteria when the bacteria were part of a polymicrobial infection than when no other pathogens were present.
“All three species-specific antibiotics were less effective against their targets when all three pathogens were present together,” said Martin Welch, Professor of Microbial Physiology and Metabolism in the Department of Biochemistry at the University of Cambridge and senior author of the paper.
Currently, antibiotics are typically only laboratory tested against the primary pathogen they are designed to target to determine the lowest effective dose. But when the same dose is used to treat a person’s infection, it often doesn’t work, and this study helps explain why. The new model system will enable the effectiveness of potential new antibiotics to be tested against mixtures of microbial species.
Polymicrobial infections are common in the airways of cystic fibrosis patients. These infections often persist for a long time despite treatment with high doses of antibiotics. Chronic airway infections in asthma and chronic obstructive pulmonary disease (COPD) patients are also often multi-microbial.
By looking at the genetic code Pseudomonas In the lab-grown mixture, the researchers were able to pinpoint the specific mutation responsible for this antibiotic resistance. Mutations were found to occur more frequently when other pathogens were also present.
Comparison with genetic code of 800 samples Pseudomonas Researchers from around the world have revealed that these mutations also occur in human patients who have been infected with the virus. Pseudomonas and treated with colistin.
“The problem is that once you treat a microbial infection with an antibiotic, the microbes start to develop resistance to that antibiotic. This is what has happened since colistin started in the early 1990s. This is another reminder of the urgent need to find new antibiotics to treat human infections,” Welch said.