Microbial communities where cells cooperate have increased drug
tolerance
Date:
March 21, 2022
Source:
The Francis Crick Institute
Summary:
Research has revealed a key mechanism which increases tolerance
to drugs amongst microbial communities. The findings could help
the development of more effective antifungal treatments.
FULL STORY ========================================================================== Research from the Francis Crick Institute has revealed a key mechanism
which increases tolerance to drugs amongst microbial communities. The
findings could help the development of more effective antifungal
treatments.
========================================================================== Antimicrobial drug resistance and tolerance occurs when bacteria,
viruses, fungi or parasites no longer respond, or have less sensitivity,
to treatments.
It is a major issue within medicine, for example, invasive fungal
infections are responsible for 1.6 million deaths annually.
"Around the world, more people die each year from invasive fungal
species than from malaria. There are currently only three classes of
antifungal drugs in clinical use and in an increasing number of cases,
these antifungals fail.
Understanding the mechanisms which increase or decrease the chance of
a drug working is crucial to aid the developments of new treatments,"
explains Jason Yu, co-first author and postdoctoral training fellow in
the Molecular Biology of Metabolism Laboratory at the Crick.
In their study, published in Nature Microbiology today (Monday 21 March),
the scientists analysed data from 12,000 microbial communities from all
over the world, provided by the Earth Microbiome Project.
Within these groups of different microorganisms, which live together
producing and absorbing materials they all need to survive and grow, the researchers found one type in particular was highly prevalent. Auxotrophs, which are unable to create essential metabolites, like amino acids,
vitamins or fatty acids, were present in 99.95% of the 12,538 communities
they studied.
Clara Correia-Melo, co-first author and researcher in the Molecular
Biology of Metabolism Laboratory at the Crick and the Department
of Biochemistry at University of Cambridge, says: "The widespread
nature of auxotrophs has been considered a paradox, a fundamental
problem in our understanding of microbiology. This is because they
must absorb metabolites from the environment and so they have been
thought of as weaker than other cells which can create these chemical
compounds themselves. They have been seen as scrounger cells, a drain on communal resources." By analysing drug exposure data from the project,
the scientists found that communities with auxotrophs are more likely
to have tolerance against hundreds of drugs, than communities without
these cells. Moreover, the research showed that they are not scrounger
cells, but rather cooperative partners as, in exchange for taking up metabolites that are essential for them, they return other metabolites
to the community.
Further experiments using a yeast model showed that this increased
tolerance is because cells that cooperate in metabolism, have increased
levels of metabolic export, the movement of metabolites out of cells. As
a side-effect, this also causes drugs to be moved out of cells at a
higher rate.
Clara Correia-Melo adds: "This work solves a paradox around
auxotroph success by revealing how auxotrophs are very valuable
to their communities. They increase the metabolic interactions
within the communities, and by doing so, increase the tolerance to
drugs. Additionally, the increase in metabolic flow also leads to an
enrichment of the shared environment, with more supplies available that
can be used for growth and survival." Markus Ralser, senior author and
group leader of the Molecular Biology of Metabolism Laboratory at the
Crick and head of the Institute of Biochemistry at Charite', a leading university hospital in Berlin adds: "Our observations go beyond microbial ecology, they open a whole field of research exploring the contribution
of metabolism and the metabolic environment to antimicrobial resistance.
"We hope that this will allow the design of new generations of
antifungals, that target not only cell growth but also tolerance, and
hence will be more effective than the currently available treatments."
The researchers will continue this work, collecting clinically relevant
fungal species and analysing their response to antimicrobials.
========================================================================== Story Source: Materials provided by The_Francis_Crick_Institute. Note:
Content may be edited for style and length.
========================================================================== Journal Reference:
1. Yu, J.S.L., Correia-Melo, C., Zorrilla, F. et al. Microbial
communities
form rich extracellular metabolomes that foster metabolic
interactions and promote drug tolerance. Nat Microbiol, 2022 DOI:
10.1038/s41564-022- 01072-5 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220321132141.htm
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