Researchers have
identified a protein that powers the virulence of the bacteria that causes gonorrhea,
opening the possibility of a new target for antibiotics and, even better, a
vaccine.
The findings, published today in PLOS Pathogens,
are especially important since the microbe, Neisseria
gonorrhoeae, is considered a "superbug" because of its resistance
to all classes of antibiotics available for treating infections.
Gonorrhea, a sexually transmitted disease that results in
78 million new cases worldwide each year, is highly damaging if untreated or
improperly treated.
It can lead to endometritis, pelvic inflammatory disease,
ectopic
pregnancy, epididymitis and infertility. Babies born to infected mothers
are at increased risk of blindness.
"The infections very often are silent," said
Oregon State University researcher Aleksandra Sikora. "Up to 50 percent of
infected women don't have symptoms, but those asymptomatic cases can still lead
to some very severe consequences for the patient's reproductive health, miscarriage
or premature delivery."
The need for better antibiotic therapy, and a vaccine, is
pressing. N. gonorrhoeae strains resistant to the last effective treatment
options have emerged, and failures in treatment are occurring.
Sikora and her research team at the OSU/OHSU College of
Pharmacy and Ann Jerse's lab at the Uniformed Services University of the Health
Sciences in Bethesda, Maryland, collaborated to discover a novel lipoprotein
that N. gonorrhoeae uses to defeat the body's first line of innate
immune defense.
The body relies on enzymes known as lysozymes that, as
their name suggests, thwart bacteria by causing their cell wall to lyse, or
break apart. Lysozymes are abundant both in epithelial cells, which make up the
tissue on the outside of organs and the inside of body cavities, and in the phagocytic
cells that protect the body by ingesting foreign particles and bacteria.
In turn, many gram-negative bacteria -- characterized by
their cell envelope that includes a protective outer membrane -- have developed
ways of defeating lysozymes. Prior to the work by Sikora's team, however, only
one lysozyme-fighting protein had been discovered in the Neisseria genus.
Now that new targets have been identified, they can be
explored as bullseye candidates for new antibiotics
or a vaccine -- if the lysozyme inhibitor can itself be inhibited, then the
bacteria's infection-causing ability is greatly reduced.
Sikora and her collaborators named the new protein SliC,
short for surface-exposed lysozyme inhibitor of c-type lysozyme.
Studying SliC's function in culture as well as in a
gonorrhea mouse model -- mice were infected with N. gonorrhoeae, then checked
for SliC expression at one, three and five days -- researchers determined the
protein was essential to bacterial colonization because of its anti-lysozyme
role.
"This is the first time an animal model has been
used to demonstrate a lysozyme inhibitor's role in gonorrhea
infection," Sikora said. "Together, all of our experiments show
how important the lysozyme inhibitor is. This is very exciting."
Abstract submission for the conference STD 2018 held
at Toronto, Canada on August 20-21, 2018 is welcome!! Submit your abstract
here: https:/std-hiv-aids.cmesociety.com/abstract-submission
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