Release Subtitle: Scientists identify an important protein
that increases “bacterial virulence,” when mutated, changing harmless
bacteria to harmful ones
Release Summary Text:
We all know that there are “good” and “bad” bacteria, but scientists
have little insight into how bacteria become “bad” or “pathogenic” and
cause disease. Now, in a new study published in PLoS Pathogens, a team
of scientists from Okayama University, Japan, described how mutations
resulting in the malformation of the lipopolysaccharide transporter—an
essential protein for bacterial growth—caused a non-pathogenic
Escherichia coli strain to become pathogenic.
Full text of release:
As far as humans are concerned, bacteria can be classified as either
harmful, pathogenic bacteria and harmless or beneficial non-pathogenic
bacteria. To develop better treatments for diseases caused by pathogenic
bacteria, we need to have a good grasp on the mechanisms that cause
some bacteria to be virulent. Scientists have identified genes that
cause virulence, or capability to cause disease, but they do not fully
know how bacteria evolve to become pathogenic.
To find out, Professor Chikara Kaito and his team of scientists from
Okayama University, Japan, used a process called experimental evolution
to identify molecular mechanisms that cells develop to gain useful
traits, and published their findings in PLoS Pathogens. “We’re excited
by this research because no one has ever looked at virulence evolution
of bacteria in an animal; studies before us looked at the evolution in
cells,” said Prof Kaito.
The scientists decided to start with a non-pathogenic Escherichia coli
(or E. coli for short) and repeatedly mutate it and use it to infect
silkworms, an insect that is often used as a model for infectious
diseases, and then test whether it will cause death in silkworms.
Through this experiment, the scientists created E. coli strains with a
500-fold increased virulence compared to the original bacterial strain
and found that mutations in the gene that code for one specific protein,
the “lipopolysaccharide transporter (LPS) transporter,” was one of the
reasons for the increased virulence. This protein forms a part of the
bacterial cell membrane and protects the bacteria from harm. Because of
this, the LPS transporter is necessary for E. coli to grow.
The mutations that increased bacterial deadliness appeared to give E.
coli resistance against some antibiotics, as well as some antibacterial
substances from the silkworms. The reason for this is likely a
corresponding increase in the concentration of structures called outer
membrane vesicles, which the bacteria release to absorb harmful
compounds to prevent them from entering the bacteria and harming them.
Researchers also identified the characteristics of substances that
pathogenic strains were resistant to, showing that they were
“hydrophobic” (or water-repelling) and positively charged. This fit with
the increased amount of outer membrane vesicles, which are hydrophobic
and negatively charged, allowing them to hold onto those substances
(because, of course, opposite forces attract). The scientists also
showed that the mutations occurred in parts of LPS transporter that are
directly on the outside of the bacterial membrane. The scientists
suspect that this is because these areas are more exposed to the
environment, thereby experience more natural selection, and are thereby
more susceptible to mutation.
“What we’ve done here is identify several things about pathogenic
bacteria,” explains Prof Kaito. “We showed for the first time that
mutations to LPS transporter can increase virulence, and we provided
evidence for how that virulence actually happens—the mutant bacteria
make more outer membrane vesicles.” And that’s not all, the team also
pinpointed specific structural changes to mutated LPS transporter that
could explain why virulence is different across bacteria—because each
species might have a different structure.
When asked about how his work contributes to scientific understanding
and to medicine, Prof Kaito elaborates, “Before our study, it wasn’t
very clear how bacteria actually evolved properties that made them more
harmful, so our study helps clarify this. An understanding of this
process means the possibility of creating drugs or other therapy that
can keep bacteria from becoming pathogenic, especially if we find more
proteins like LPS transporter, where mutations can have such a big
effect.”
Of course, further studies are needed to explore whether the mutations
observed in this study will also increase virulence when the bacteria
infect animals bigger than silkworms, like mammals. But this study is
definitely the first step toward unraveling the mystery of differences
between dangerous and harmless bacteria.
Release URL: https://www.eurekalert.org/pub_releases/2020-06/ou-fjt062520.php
Reference:
Title of original paper: Non-pathogenic Escherichia coli acquires virulence by mutating a growth-essential LPS transporter
Journal: PLoS Pathogens
DOI: http://dx.doi.org/10.1371/journal.ppat.1008469
Contact Person: KAITO Chikara
E-mail: ckaito(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
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