OKAYAMA, Japan, Nov. 30, 2020
/PRNewswire/ -- In a study recently published in PLoS Pathogens,
researchers at Okayama University reveal novel mutations which transform
bacteria into infectious bugs that are resistant to antibiotics.
Not all bacteria are naturally infectious. Several strains of
innocuous bacteria turn infectious over their lifespan. However, the
mechanisms by which such bacteria acquire pathogenic properties (known
as virulence in microbiology terms) are still a mystery. Now, a research
team led by Professor KAITO Chikara from Okayama University has identified specific gene mutations which drive this deadly switch in the microorganisms.
The researchers employed a non-pathogenic strain of Escherichia coli,
bacteria commonly used in the laboratory, and exposed them to
mutation-inducing processes. The bacteria were subsequently injected
into silkworms. After multiple rounds of mutagen exposure, the E.coli
started swiftly killing the worms, turning 500 times more lethal at a
certain point. A closer look at the DNA of this dangerous strain
revealed mutations in a protein known as the lipopolysaccharide (LPS)
transporter. The LPS transporter resides on the bacterial membrane and
funnels LPS, a bacterial toxin, from within the cell onto its surface.
To understand how these mutations were linked to bacterial toxicity, the
mutant E.coli were treated with host antimicrobial peptides or
antibiotics. These antimicrobial molecules, however, did not hamper the
growth of the mutant bacteria suggesting that the mutants had developed
resistance against host immune response and antibiotics.
Bacteria store an arsenal of chemicals on their surface within small
vesicles. The mutant E.coli had an abundance of such vesicles which were
also rich in LPS. It thus seemed that the bugs had developed a clever
mechanism to expel toxins and chemicals out of the cell. The team then
analysed the LPS transporter to investigate whether its mutations played
a role in this regard. Indeed, the structure of the LPS transporter was
found altered in the mutant strains. A plug which keeps the channel of
the transporter closed, appeared defective. Lastly, to see whether
similar mutations in the LPS transporter occur naturally, the team
examined bacterial samples taken from patients. As expected, these
samples contained similar mutants of E.coli which were also resistant to
antimicrobials. Mutations in the LPS transporter were thus conferring
bacteria with crafty mechanisms to stay alive and infect host cells.
"These findings suggest that non-pathogenic bacteria can gain
virulence traits by changing the functions of essential genes, and
provide new insight to bacterial evolution in a host environment,"
conclude the researchers. Information on such toxic mutations in
bacteria are vital for diagnosing infections and developing appropriate
antibacterial drugs.
Background
Virulence – A microorganism's ability to infect a host cell is known
as virulence. Organisms have varying mechanisms of virulence known as
virulence factors. Common virulence factors driving bacterial toxicity
are chemicals that help bacteria invade and adhere to host cells or
poisons that damage host cells. A thorough understanding of these
factors is key to developing strategies for combatting bacterial
toxicity.
Lipopolysaccharide (LPS) – LPS is a chemical that forms a major
component of the outer membrane of bacteria. Once synthesized within the
bacterial cell, it is pushed out through a channel known as the LPS
transporter to subsequently reside within the outer membrane. LPS
protects the bacterial membrane from foreign attacks and induces
responses such as inflammation, fever, and septic shock when bacteria
infect hosts. Thus, LPS is a crucial component of the bacterial defense
system.
Reference
Chikara Kaito, Hirono Yoshikai, Ai Wakamatsu, Atsushi Miyashita, Yasuhiko Matsumoto, Tomoko Fujiyuki, Masaru Kato, Yoshitoshi Ogura, Tetsuya Hayashi, Takao Isogai,
Kazuhisa Sekimizu. Non-pathogenic Escherichia coli acquires virulence
by mutating a growth-essential LPS transporter. PLoS Pathogens, 2020
Apr; 16(4): e1008469.
DOI : 10.1371/journal.ppat.1008469
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008469
Related Figure
https://www.okayama-u.ac.jp/up_load_files/research_highlights/117_image_1.jpg
Caption
Induction of ischemia (lack of oxygen) resulted in a considerable
decrease in healthy cells and contractility (red = highest contractions
and blue = lowest contractions) compared to the control group which had
normal oxygen levels throughout the experiment.
Correspondence to
Professor KAITO Chikara, Ph.D.
Division of Immunobiology,
Graduate School of Medicine, Dentistry and Pharmaceutical
Sciences, Okayama University, 1-1-1, Tsushima-naka, Kita-ku,
Okayama 700-8530, Japan
e-mail : ckaito(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
http://www.pharm.okayama-u.ac.jp/lab/bunsei/
Further information
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