The S. sonnei
bacteria has been associated with major shigellosis outbreaks in California in 2014 and 2015.
In a study that could have significant impact on how disease
outbreaks are managed, researchers at UC Davis and the California
Department of Public Health (CDPH) have sequenced and analyzed genomes
from S. sonnei
‘Genomic sequencing and analysis of Shigella sonnei bacteria could offer new insights into how the bacteria acquired virulence and antibiotic resistance genes.’
The results offer new insights into how the bacteria acquired
virulence and antibiotic resistance genes, as well as the California
strains' relationships to other strains around the world. This was the
first major, whole-genome study of S. sonnei
strains found in North America. The research was published in the journal mSphere
"If you have an outbreak and you want to know what is causing a
particular problem, like antibiotic resistance, sequencing the genome
can identify the genes involved," said Jonathan Eisen, professor with
appointments in the Department of Medical Microbiology and Immunology
and the Department of Evolution and Ecology at UC Davis and a
collaborator on the study.
"Eventually, we should be able to sequence whole genomes of bacteria to support patient care," he said.
The investigators from the Microbial Diseases Laboratory at CDPH
sequenced the genomes of 68 isolates, including samples from the recent
California outbreaks and historical strains from California, Asia and
elsewhere. They also tested for antibiotic resistance.
The team found two clusters in these outbreaks: one that primarily
struck San Diego and the San Joaquin Valley and one more localized to
the San Francisco Bay Area.
The San Diego/San Joaquin strain has been in California since at
least 2008. However, some of the isolates had been infected with a
bacteriophage (a virus that attacks bacteria) that carried a Shiga toxin
(STX) gene found in the more virulent S. flexneri and S. dysenteriae.
bacteria normally cause a less severe
disease and are not known to produce Shiga toxin," said Dr. James Watt,
Chief, Division of Communicable Disease Control at CDPH.
"The toxin gene was most likely acquired by Shigella sonnei
via genetic exchanges with E. coli and other Shigella species.
Discovering a functional toxin gene was concerning in this large
outbreak. Finding this gene raises concerns that illness due to Shigella sonnei
could become more severe in the future," Watt said.
By contrast, the strain that hit San Francisco lacked STX but
contained genes that gave it resistance to the broad-spectrum
fluoroquinolone class of antibiotics. The fluoroquinolone-resistance
genes were similar to ones found in strains from Southeast Asia. These
findings provide important clues to the strains' origins.
"We know these movements of DNA can be important for the spread of
antibiotic resistance, virulence and pathogenicity factors," Eisen said.
"Having the genome data from outbreaks allows us to try to figure out
The researchers believe similar studies might ultimately benefit
patients. Understanding a pathogen's genetic variants could inform
antibiotic choices and even help improve hospital procedures.
"If you can show that the transfer of antibiotic resistance genes
came in response to some kind of treatment, you would certainly think
about isolating people who were receiving that treatment, potentially
sampling them more often or even changing treatments," explained Eisen.
Before that can happen, genomic sequencing must become a routine part of the nation's pathogen-surveillance model.
"It is clear, from a technical, economic, and scientific point of
view, that we can and should be integrating more genome sequencing into
infectious disease studies," Eisen said.