Genetic diversity of C. difficile, a particularly problematic pathogen

Researchers at the University of California San Diego School of Medicine and Jacobs School of Engineering, along with colleagues at Baylor College of Medicine, used a systems biology approach to analyze C genetic diversity.difficult perrididioidsa pathogen especially problematic in healthcare settings.

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

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

It is difficult is the leading cause of hospital-acquired infections, in part due to the use of antibiotics, which can kill enough healthy bacteria to allow C. difficile to grow uncontrollably. Infections are especially dangerous in the elderly. One in 11 people over the age of 65 diagnosed It is difficult He will die in a month, the CDC reports.

C difference. is persistent and widespread, “said lead author Jonathan M. Monk, PhD, researcher in the UC San Diego Systems Biology Research Group, led by Bernhard O. Palsson, PhD, professor of bioengineering and adjunct professor at UC San Diego School of Medicine. “It does not cause typical diarrhea. Most people recover, but some become seriously ill, require hospitalization, and some die from complications such as kidney failure or sepsis. »

To better understand the genetic characteristics of It is difficult —And thus developing models capable of identifying and predicting their complex and constant evolution — the researchers used genome-wide sequencing, high-yield phenotypic screening, and metabolic modeling of 451 bacterial strains.

This data was used to construct a “pangenoma” or a complete set of genes representative of all known genes. It is difficult strains, from which they identified 9,924 different gene groups, of which 2,899 were considered essential (found in all strains) while 7,025 were “accessories” (present in some strains but missing in others).

Using a new method of writing, they classified 176 groups of genetically different stems.

“Accessory genome typing allows the discovery of newly acquired genes in the genomes of pathogens that might otherwise go unnoticed by standard typing methods,” said co-author Jennifer K. Spinler, PhD, professor of Pathology and Immunology at Baylor College of Medicine. “This could be key to understanding what drives an outbreak and how to control its spread.”

Thirty-five strains representing the overall set were experimentally profiled with 95 different nutrient sources, revealing 26 different growth profiles. The team then constructed 451 genome-specific metabolism models to calculate phenotypic diversity under 28,864 unique conditions. The models were able to correctly predict growth in 76% of the measured cases.

“One of the strengths of the work presented is the cohesion of different types of biological data into comprehensive systems biology frameworks that allow for large-scale analysis,” said lead author Charles J. Norsigian, PhD, data within the group. systems biology research. “In interpreting strains of It is difficult in a population context, we were able to shed light on the relevant characteristics of the strain in terms of nutrient niche, virulence factors, and determinants of antimicrobial resistance that would otherwise have gone unnoticed.

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’s Ames Research Center.

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Materials provided by University of California-San Diego. Original written by Scott LaFee. Note: Content can be edited by style and length.

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