Effectiveness of antibiotics significantly reduced when multiple bugs
present

Date:
March 19, 2022
Source:
University of Cambridge
Summary:
A study has found that much higher doses of antibiotics are needed
to eliminate a bacterial infection of the airways when other
microbes are present. It helps explain why respiratory infections
often persist in people with lung diseases such as cystic fibrosis
despite treatment.



FULL STORY ==========================================================================
A study has found that much higher doses of antibiotics are needed to
eliminate a bacterial infection of the airways when other microbes are
present. It helps explain why respiratory infections often persist in
people with lung diseases such as cystic fibrosis despite treatment.


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In the study, published today in The ISME Journal, researchers say that
even a low level of one type of microbe in the airways can have a profound effect on the way other microbes respond to antibiotics.

The results highlight the need to consider the interaction between
different species of microbe when treating infections with antibiotics --
and to adjust dosage accordingly.

"People with chronic infections often have co-infection with several
pathogens, but the problem is we don't take that into account in deciding
how much of a particular antibiotic to treat them with. Our results might
help explain why, in these people, the antibiotics just don't work as
well as they should," said Thomas O'Brien, who carried out the research
for his PhD in the University of Cambridge's Department of Biochemistry
and is joint first author of the paper.

Chronic bacterial infections such as those in the human airways are very difficult to cure using antibiotics. Although these types of infection
are often associated with a single pathogenic species, the infection
site is frequently co-colonised by a number of other microbes, most of
which are not usually pathogenic in their own right.

Treatment options usually revolve around targeting the pathogen, and
take little account of the co-habiting species. However, these treatments
often fail to resolve the infection. Until now scientists have had little insight into why this is.



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To get their results the team developed a simplified model of the human airways, containing artificial sputum ('phlegm') designed to chemically resemble the real phlegm coughed up during an infection, packed with
bacteria.

The model allowed them to grow a mixture of different microbes, including pathogens, in a stable way for weeks at a time. This is novel, because
usually one pathogen will outgrow the others very quickly and spoil the experiment. It enabled the researchers to replicate and study infections
with multiple species of microbe, called 'poly-microbial infections',
in the laboratory.

The three microbes used in the experiment were the bacteria Pseudomonas aeruginosaandStaphylococcus aureus,and the fungus Candida albicans --
a combination commonly present in the airways of people with cystic
fibrosis.

The researchers treated this microbial mix with an antibiotic called
colistin, which is very effective in killing Pseudomonas aeruginosa.But
when the other pathogens were present alongside Pseudomonas aeruginosa,the antibiotic didn't work.

"We were surprised to find that an antibiotic that we know should clear an infection of Pseudomonaseffectively just didn't work in our lab model when other bugs were present," said Wendy Figueroa-Chavez in the University of Cambridge's Department of Biochemistry, joint first author of the paper.



==========================================================================
The same effect happened when the microbial mix was treated with fusidic
acid - - an antibiotic that specifically targets Staphylococcus aureus,and
with fluconazole -an antibiotic that specifically targetsCandida albicans.

The researchers found that significantly higher doses of each antibiotic
were needed to kill bacteria when it was part of poly-microbial infection, compared to when no other pathogens were present.

"All three species-specific antibiotics were less effective against their target when three pathogens were present together," said Martin Welch, Professor of Microbial Physiology and Metabolism in the University of Cambridge's Department of Biochemistry and senior author of the paper.

At present antibiotics are usually only laboratory tested against the
main pathogen they are designed to target, to determine the lowest
effective dose.

But when the same dose is used to treat infection in a person it often
doesn't work, and this study helps to explain why. The new model system
will enable the effectiveness of potential new antibiotics to be tested
against a mixture of microbe species together.

Poly-microbial infections are common in the airways of people with
cystic fibrosis. Despite treatment with strong doses of antibiotics,
these infections often persist long-term. Chronic infections of the
airways in people with asthma and chronic obstructive pulmonary disorder
(COPD) are also often poly- microbial.

By looking at the genetic code of the Pseudomonasbacteria in their
lab-grown mix, the researchers were able to pinpoint specific mutations
that give rise to this antibiotic resistance. The mutations were found
to arise more frequently when other pathogens were also present.

Comparison with the genetic code of 800 samples ofPseudomonasfrom around
the world revealed that these mutations have also occurred in human
patients who had been infected with Pseudomonas and treated with colistin.

"The problem is that as soon as you use an antibiotic to treat a microbial infection, the microbe will start to evolve resistance to that antibiotic.

That's what has happened since colistin started to be used in the
early 1990's.

This is another reminder of the vital need to find new antibiotics to
treat human infections," said Welch.


========================================================================== Story Source: Materials provided by University_of_Cambridge. The original
text of this story is licensed under a Creative_Commons_License. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Thomas James O'Brien, Wendy Figueroa, Martin Welch. Decreased
efficacy of
antimicrobial agents in a polymicrobial environment. The ISME
Journal, 2022; DOI: 10.1038/s41396-022-01218-7 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220319081652.htm

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