Whole Genome Sequencing Speeds Analysis of Shigella Outbreak in California

Dr-Varvara-Kozyreva.jpg

Dr. Varvara Kozyreva

MedicalResearch.com Interview with:
Varvara Kozyreva, PhD
Research Scientist Supervisor I
Genotyping Unit
Foodborne & Waterborne Diseases Section (FWDS)
Microbial Diseases Laboratory Program (MDL)
Division of Communicable Disease Control (DCDC)
Center for Infectious Diseases (CID)
California Department of Public Health (CDPH)
Richmond, CA 94804
California Department of Pubic Health

MedicalResearch.com: What is the background for this study?

CDPH Response: Two large shigellosis outbreaks occurred in San Diego and San Joaquin Counties of California in 2014-2015.

Shigellosis is caused by bacteria of Shigella genus and manifests itself as abdominal pain, diarrhea and other gastrointestinal symptoms. Each year, shigellosis causes around 500,000 infections, 6,000 hospitalizations and 70 deaths in the U.S. The shigellosis outbreaks in California were caused by a rare strain of Shiga-toxin producing Shigella sonnei bacteria. Shigella sonnei normally causes a relatively mild disease and is not known to produce Shiga-toxin. The emergence of this Shiga-toxin producing strain in California was unusual and concerning that shigellosis could become more severe in the future.

The California Department of Public Health Microbial Diseases Laboratory in collaboration with UC Davis tried to understand the origin of the Shigella sonnei strains circulating in California, how the bacteria acquired the Shiga-toxin gene and antibiotic resistance, as well as the relationships of California strains to other lineages around the world. This was the first major whole-genome study of Shigella sonnei bacteria in North America. In order to accomplish this we have sequenced and analyzed genomes of the recent outbreak strains as well as historical Shigella sonnei isolates from our archive going back as far as 1980. We also compared the genomes of California bacteria to other Shigella sonnei genomes from around the world. Among recent isolates we found two distinct outbreak populations: the Shiga-toxin producing strain primarily localized to San Diego and the San Joaquin Valley area, and the strain from the San Francisco Bay Area remarkable for its resistance to broad range of antibiotics.

MedicalResearch.com:  What are the main findings?

CDPH Response: Comprehensive analysis of genomes revealed a common origin of the toxin-producing strains of Shigella sonnei and their connection to earlier strains circulating in California. We learned that these microorganisms were not introduced to California but have originated locally.

It appeared that the toxin gene was introduced to Shigella sonnei with the Shiga-toxin encoding bacteriophage, the virus of bacteria, which interjected itself into Shigella sonnei genome. Most likely this happened via genetic exchange with Escherichia coli and other Shigella species. Furthermore, the bacteriophage in Shigella sonnei from California was very similar to a bacteriophage of Escherichia coli strain, which has caused a large outbreak in Europe in 2011.

 MedicalResearch.com: What should readers take away from this report?

CDPH Response: Whole Genome Sequencing (WGS) of Shigella sonnei allowed in-depth analysis of outbreak strains in California. The knowledge helped strengthen earlier epidemiological analysis of the outbreaks and understand the emerging trends in Shigella sonnei populations circulating in California.

The recent shigellosis outbreaks in California are characterized by two trends: 1) an acquisition of a new virulence factor (Shiga-toxin) by a local bacteria and 2) introduction of the antibiotic-resistant strain from abroad. It demonstrates two possible ways for the pathogens of high public health concern to emerge. This highlights the importance of monitoring the emergence and dissemination of the virulence and antibiotic resistance genetic determinants as well as shifts in local pathogen populations and flow of the bacterial strains between the countries and continents.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

CDPH Response:  Whole Genome Sequencing (WGS) of Shigella sonnei allowed in-depth analysis of outbreak strains in California. The knowledge helped strengthen earlier epidemiological analysis of the outbreaks and understand the emerging trends in Shigella sonnei populations circulating in California.

The recent shigellosis outbreaks in California are characterized by two trends: 1) an acquisition of a new virulence factor (Shiga-toxin) by a local bacteria and 2) introduction of the antibiotic-resistant strain from abroad. It demonstrates two possible ways for the pathogens of high public health concern to emerge. This highlights the importance of monitoring the emergence and dissemination of the virulence and antibiotic resistance genetic determinants as well as shifts in local pathogen populations and flow of the bacterial strains between the countries and continents.

MedicalResearch.com: Is there anything else you would like to add:
CDPH Response:
1. Additional genome analysis of Shigella sonnei is needed to find out if other bacterial traits influence their pathogenic properties.
2. Researchers should foster communications with the healthcare professionals to increase awareness about the potential for serious infectious due to Shigella sonnei.
3. More widespread use of Whole Genome Sequencing (WGS) in public health laboratories would help outbreak investigations, characterization of pathogenic properties of the bacteria and detection of antibiotic resistance genes. This would create a more complete picture of the bacterial world surrounding us, and in turn, help to protect public health

Citation:

Recent Outbreaks of Shigellosis in California Caused by Two Distinct Populations of Shigella sonnei with either Increased Virulence or Fluoroquinolone Resistance
Varvara K. Kozyreva, Guillaume Jospin, Alexander L. Greninger, James P. Watt, Jonathan A. Eisen, Vishnu Chaturvedi
Melanie Blokesch, Editor
DOI: 10.1128/mSphere.00344-16

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Magdalena Cerda, DrPH, MPH Vice Chancellor's Chair in Violence Prevention Associate Director, Violence Prevention Research Program UC Davis Violence Prevention Research Program

Dr. Magdalena Cerda

Magdalena Cerda, DrPH, MPH
Vice Chancellor’s Chair in Violence Prevention
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Diana Miglioretti, PhD

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Associate Professor of Pathology and Infectious Diseases
University of California, Davis School of Medicine
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Associate Professor
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Robert J Canter MD
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