あなたはここにいる:ホーム > お知らせ > 業界動向 > Potential Pathway to...
著者: アップロード:2017-09-21 閲読回数:
Scientists at the Houston
Methodist Research Institute say they have found an important target on
which to focus for developing a potential Group A Streptococcus (GAS) vaccine or antibiotic to fight
it. GAS infections cause several million cases of strep throat every year,
but also can lead to more severe infections, such as flesh-eating disease and
acute rheumatic heart disease, according to the researchers.
By manipulating this target, they hope to either reduce the severity of
these infections or clear them up faster.
Muthiah Kumaraswami, Ph.D.,
an infectious diseases researcher at Houston
Methodist Hospital,
is the corresponding author and principal investigator in an article
("Leaderless Secreted Peptide Signaling Molecule Alters Global Gene
Expression and Increases Virulence of a Human Bacterial Pathogen”) that
appears in PNAS. Dr.
Kumaraswami and his team discovered a peptide secreted by the bacteria
that signals its neighbors to produce streptococcal pyrogenic exotoxin B
(SpeB), which is critical for the development of necrotizing fasciitis, better
known as flesh-eating disease. Blocking production of that toxin will be
crucial for disease prevention and treatment.
"We have discovered
that GAS uses a previously unknown peptide-mediated intercellular signaling
system to control SpeB production, alter global gene expression, and enhance
virulence. GAS produces an eight-amino acid leaderless peptide [SpeB-inducing
peptide (SIP)] during high cell density and uses the secreted peptide for
cell-to-cell signaling to induce population-wide speB expression. The SIP signaling
pathway includes peptide secretion, reimportation into the cytosol, and
interaction with the intracellular global gene regulator Regulator of Protease
B (RopB), resulting in SIP-dependent modulation of DNA binding and regulatory
activity of RopB,” write the investigators.
“SIP signaling causes differential expression of ∼14% of GAS core genes. Several genes that encode toxins and other virulence genes that enhance pathogen dissemination and infection are significantly up-regulated. Using three mouse infection models, we show that the SIP signaling pathway is active during infection and contributes significantly to GAS pathogenesis at multiple host anatomic sites. Together, our results delineate the molecular mechanisms involved in a previously undescribed virulence regulatory pathway of an important human pathogen and suggest new therapeutic strategies."
"Researchers have
known for more than 100 years that GAS uses the toxin SpeB and that it is
crucial to disease development," Dr. Kumaraswami said. "We did
not know, however, what signals the timely production of SpeB by GAS. Now that
we have discovered how GAS bacteria communicate with each other to coordinate
the production of this toxin, we can target the signaling pathway for vaccine
and antimicrobial development."
Dr. Kumaraswami says that
bacteria interacting and producing toxins is not new. Their communication codes
have been characterized for a long time, so researchers know a lot of the
classic features in these signals. What's different in what his team discovered
is the nature of the language. The GAS communication signal they found lacks a
majority of those classic hallmarks.
"Typically, the signal
is quite long and has a number of characteristic features," Dr.
Kumaraswami explains. "The signal we found is compact and doesn't have
many of what we traditionally see in other bacterial peptides, which is
probably what contributed to the difficulties in finding it for such a long
time. There could be similar atypical signals in other bacteria that have been
overlooked, as well, so we believe the discovery of this peptide will likely
facilitate discovering additional bacterial peptide signals in other
pathogens."