Genetic diversity of C. difficile, a particularly problematic pathogen — ScienceDaily

Researchers from the University of California San Diego School of Medicine and Jacobs School of Engineering, along with colleagues from Baylor College of Medicine, used a systems biology approach to analyze the genetic diversity of Cdifficult perrididioidesa particularly problematic pathogen in healthcare settings.

The Centers for Disease Control estimate that the bacteria causes around 500,000 infections in the United States each year, with severe diarrhea and colitis (inflammation of the colon) as hallmark symptoms.

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

It’s hard 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 unchecked. Infections are especially dangerous in the elderly. One in 11 people over the age of 65 who are diagnosed with a nosocomial illness It’s hard die within a month, reports the CDC.

C difference. is persistent and pervasive,” said lead author Jonathan M. Monk, PhD, a researcher with the Systems Biology Research Group at UC San Diego, led by Bernhard O. Palsson, PhD, professor of bio -engineering and adjunct professor at UC San Diego School of Medicine. “It doesn’t cause typical diarrhoea. Most people recover, but some get seriously ill, need hospitalization, and some die of complications like kidney failure or sepsis.”

To better understand the genetic characteristics of It’s hard — and thus develop models capable of identifying and predicting its complex and constant evolution — the researchers used whole genome sequencing, high-throughput phenotypic screening and metabolic modeling of 451 bacterial strains.

These data were used to construct a “pangenome” or a complete set of genes representative of all known genes. It’s hard strains, from which they identified 9,924 distinct gene clusters, of which 2,899 were considered essential (found in all strains) while 7,025 were “accessory” (present in some strains but missing in others).

Using a new typing method, they classified 176 genetically distinct stem groups.

“Accessory genome typing enables the discovery of newly acquired genes in the genomes of pathogens that might otherwise go undetected with 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 distinct growth profiles. The team then constructed 451 strain-specific genome-wide metabolism models to compute phenotypic diversity under 28,864 unique conditions. The models were able to correctly predict growth in 76% of the cases measured.

“One of the strengths of the work presented is the cohesion of distinct biological data types into comprehensive systems biology frameworks that allow for large-scale analysis,” said first author Charles J. Norsigian, PhD, data within the systems biology research group. “By interpreting strains of It’s hard in a population context, we were able to shed light on relevant strain characteristics regarding nutrient niche, virulence factors, and antimicrobial resistance determinants that might 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 Ames Research Center.

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Material provided by University of California – San Diego. Original written by Scott LaFee. Note: Content may be edited for style and length.

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