Researchers attacking menacing `superbug'

Date:
December 2, 2021
Source:
Texas A&M University
Summary:
Scientists around the world have been working in earnest to improve
understanding of an increasingly virulent superbug, Clostridium
difficile. The highly contagious hospital-acquired pathogen,
designated by the Centers for Disease Control and Prevention as
one of the five most urgent threats to the U.S. healthcare system,
causes more than 500,000 infections and 29,000 deaths each year
at a total societal cost exceeding $5 billion.



FULL STORY ========================================================================== Scientists around the world have been working in earnest to improve understanding of an increasingly virulent superbug, Clostridium
difficile. The highly contagious hospital-acquired pathogen, designated
by the Centers for Disease Control and Prevention as one of the five
most urgent threats to the U.S. healthcare system, causes more than
500,000 infections and 29,000 deaths each year at a total societal cost exceeding $5 billion.


========================================================================== Biologists at Texas A&M University and Baylor College of Medicine have
teamed up in a novel National Institutes of Health-funded systems biology
study aimed at tackling the problem at its source -- the initial point
of infection -- in hopes of pinpointing what makes patients susceptible
to it in the first place.

Prior studies have shown C. difficileinfection to be strongly correlated
with a high abundance of secondary bile acids that are toxic to
C. difficile in laboratory settings. These small molecules are generated
by a healthy gut microbiome from primary bile acids that are synthesized
in the liver.

Texas A&M biologist and 2020 Chancellor's EDGES Fellow Joseph Sorg says scientists have long viewed these small molecules as a key protector
in preventing C. difficileinfection. The research was first featured
by Sorg Laboratory graduate student Andrea Martinez Aguirre in a paper published earlier this fall in the journal PLOS Pathogens with help from
Tor Savidge's group at Baylor College of Medicine.

"Many ongoing efforts are developing probiotic treatment options for
C. diff- infected patients -- efforts that focus on restoring secondary
bile acids to patients," Sorg said. "Our findings show that these
treatments should instead focus on microbes that consume nutrients
important for C. diff growth and that secondary bile acids are a red
herring for protection." As the basis of their study, the team used
mice derived germ-free at Baylor College of Medicine that were colonized
with a single species of bacteria known to be involved in secondary bile
acid generation and strongly correlated with a protective C. difficile environment. As an additional control measure, they selected a mutant
mouse strain purchased through the NIH's Knockout Mouse Project that
was bred at Texas A&M and distinct for its inability to synthesize a
major class of bile acids, thereby further limiting the secondary bile
acid pool.

"Surprisingly, we found that mice colonized with these microbes
(C. scindens, C. hiranonis, or C. leptum) protected against C. diff
disease but did not produce secondary bile acids," Sorg said.

Sorg joined the Texas A&M Department of Biology in 2010 and has been
working since his postdoctoral days to unlock C. difficile's basic
science, from its physiology to its virulence. He earned his doctorate
in microbiology at the University of Chicago in 2006, the same year the
C. difficile genome was sequenced, and since has emerged as one of the
pioneers of C. difficile study.

========================================================================== Story Source: Materials provided by Texas_A&M_University. Original
written by Shana K.

Hutchins. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Andrea Martinez Aguirre, Nazli Yalcinkaya, Qinglong Wu, Alton
Swennes,
Mary Elizabeth Tessier, Paul Roberts, Fabio Miyajima, Tor
Savidge, Joseph A. Sorg. Bile acid-independent protection against
Clostridioides difficile infection. PLOS Pathogens, 2021; 17 (10):
e1010015 DOI: 10.1371/journal.ppat.1010015 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211202162144.htm

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