Genetic diversity of C. difficile, a particularly problematic pathogen


Date:
April 27, 2022
Source:
University of California - San Diego
Summary:
Researchers have used a systems biology approach to parse the
genetic diversity of Clostridioides difficile, a particularly
problematic pathogen, particularly in health care settings.



FULL STORY ========================================================================== Researchers at University of California San Diego School of Medicine
and Jacobs School of Engineering, with colleagues at Baylor College
of Medicine, have used a systems biology approach to parse the genetic diversity of Clostridioides difficile, a particularly problematic pathogen
in health care settings.


==========================================================================
The Centers for Disease Control estimates that the bacterium causes approximately 500,000 infections in the United States annually, with
severe diarrhea and colitis (inflammation of the colon) as characteristic symptoms.

The researchers' findings are published in the April 27, 2022 online
issue of PNAS.

C. difficile is the most dominant cause of hospital-associated
infections, in part from the use of antibiotics, which can kill enough
healthy bacteria to allow C. difficile to grow unchecked. Infections are particularly dangerous in older persons. One in 11 people over the age
of 65 who are diagnosed with a hospital-associated case of C. difficile
die within one month, reports the CDC.

"C. diff is persistent and pervasive," said senior author Jonathan
M. Monk, PhD, a research scientist in the Systems Biology Research
Group at UC San Diego, directed by Bernhard O. Palsson, PhD, professor
of bioengineering and an adjunct professor in the UC San Diego School
of Medicine. "It doesn't cause typical diarrhea. Most people do recover,
but some become seriously ill, require hospitalization and some die from complications like kidney failure or sepsis." To better understand the
genetic features of C. difficile -- and thus develop models that can
identify and predict its complex and constant evolution - - researchers
used whole-genome sequencing, high-throughput phenotypic screening and metabolic modeling of 451 bacterial strains.

This data was used to construct a "pangenome" or entire set of genes representative of all known C. difficile strains, from which they
identified 9,924 distinct gene clusters, of which 2,899 were considered
to be core (found in all strains) while 7,025 were "accessory" (present
in some strains but missing in others).

Using a new typing method, they categorized 176 genetically distinct
groups of strains.

"Typing by accessory genome allows for the discovery of newly acquired
genes in genomes of pathogens that may otherwise go unnoticed with
standard typing methods," said co-author Jennifer K. Spinler, PhD,
an instructor in pathology and immunology at the Baylor College of
Medicine. "This could be critical in understanding what drives an
outbreak and how to fight its spread." Thirty-five strains representing
the overall set were experimentally profiled with 95 different nutrient sources, revealing 26 distinct growth profiles. The team then built 451 strain-specific genome scale models of metabolism to computationally
produce phenotype diversity in 28,864 unique conditions. The models were
able to correctly predict growth in 76 percent of measured cases.

"One of the strengths of the presented work is the cohesion of distinct biological data types into comprehensive systems biology frameworks that
enable analysis at scale," said first author Charles J. Norsigian, PhD,
a data scientist in the Systems Biology Research Group. "By interpreting strains of C.

difficile in a population context, we were able to bring to light
pertinent strain features regarding nutrient niche, virulence factors,
and antimicrobial resistance determinants that might have otherwise gone undetected." Co-authors include: Bernhard O. Palsson, UC San Diego;
Heather A. Danhof, Colleen K. Brand, Firas S. Midani, Robert A. Britton
and Tor C. Savidge, Baylor College of Medicine; and Jared T. Broddrick
and Jennifer K. Spinier, NASA Ames Research Center.


========================================================================== Story Source: Materials provided by
University_of_California_-_San_Diego. Original written by Scott
LaFee. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Charles J. Norsigian, Heather A. Danhof, Colleen K. Brand, Firas S.

Midani, Jared T. Broddrick, Tor C. Savidge, Robert A. Britton,
Bernhard O. Palsson, Jennifer K. Spinler, Jonathan M. Monk. Systems
biology approach to functionally assess the Clostridioides
difficile pangenome reveals genetic diversity with discriminatory
power. Proceedings of the National Academy of Sciences, 2022; 119
(18) DOI: 10.1073/pnas.2119396119 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220427171442.htm

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