DNA blueprint of deadly cholera bacterium unveiled

August 01, 2000

As reported in this week's issue of the journal Nature, scientists have determined the entire order of paired chemical building blocks that make up the DNA of the deadly cholera bacterium, an ancient infectious foe. The comma-shaped microbe, Vibrio cholerae, causes a severe diarrheal disease that has been endemic in southern Asia for at least 1,000 years. Since 1817, it has spread worldwide to cause seven pandemics. Between outbreaks, the organism thrives in brackish waters in both harmless and disease-causing forms.

"Determining the genomic sequence of medically important pathogens such as Vibrio cholera holds enormous promise for helping us fight some of the world's most intractable infectious diseases," comments Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), which funded the project. "Besides contributing to our understanding of how a microbe causes disease and survives in the environment, sequencing studies enable scientists to locate genes that may lead to potential new targets for vaccine candidates, drugs and diagnostic tools.

"Cholera has been extensively studied by many people, yet important new discoveries continue to be made," he adds. "Having the sequence available will facilitate these efforts immensely."

A talented team of cholera and genome sequencing experts contributed to the success of the project. They include John Mekalanos, Ph.D., of Harvard Medical School, a renowned microbiologist who probes how bacterial virulence factors cause disease; National Science Foundation Director Rita Colwell, Ph.D., of the University of Maryland, an expert in how V. cholerae persists in the environment; and genomics experts Claire M. Fraser, Ph.D., and John Heidelberg, Ph.D., of The Institute for Genomic Research (TIGR) in Rockville, Maryland .

The project began in late 1996, one of the earliest microbial genome sequencing efforts financed by NIAID, and its outcome has been long-awaited. Since that time, NIAID has rapidly expanded its portfolio of such grants, and they now number more than 30.

One of the most unusual findings of the cholera project is that instead of having one circular chromosome, like most bacteria, the organism has two, notes Dennis Lang, Ph.D., NIAID's bacterial and viral enteric diseases program officer. "When the team became aware of new research indicating that cholera strains may have two chromosomes, they rapidly assembled the final sequence into two separate elements."

The larger chromosome, comprising nearly 3 million base pairs, contains most of the organism's critical genes, including those coding for disease-causing toxins and proteins that carry out essential cell functions. The smaller chromosome is roughly one-third its size. "Both chromosomes are essential," says Dr. Lang. "You couldn't do away with either one of them and have the organism be viable."

Besides illuminating the bacterium's role in disease, the sequence information will enable scientists to investigate specific questions about how V. cholerae survives and persists in the environment, which it sometimes does by colonizing algae and other sea life. "Hundreds of different strains of the bacterium exist, and how they interact and evolve is largely a mystery," Dr. Lang notes.

Dr. Colwell and others have long believed that the bacterium enters a quiescent state where, much like bacterial spores, it is alive but fails to multiply unless triggered by specific environmental conditions. "The authors of the Nature paper found some genes in the cholera genome," Dr. Lang says, "that appear to be related to genes from sporulating bacteria. What role these cholera genes may play in that quiescent state, if it exists, remains to be seen, but this information will provide much fodder for that research."

The V. cholerae strain that was sequenced, a virulent El Tor strain used for many years in clinical studies, is also a strain that NIAID has produced in quantity and supplies to investigators worldwide for vaccine studies.

Cholera has a rapid onset and most often occurs in epidemics spread through contaminated water. Oral rehydration is an effective treatment, but left untreated, cholera causes severe diarrhea that has a high mortality rate, particularly in young children. According to information reported to the World Health Organization in 1999, nearly 8,500 people died and another 223,000 were sickened with cholera worldwide.
-end-
NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.

REFERENCES: JF Heidelberg et al. DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406:477-84 (2000).

MK Waldor and D RayChaudhuri. Treasure trove for cholera research. Nature 406:469-70 (2000).

For more information on NIAID's support of microbial genome sequencing projects, visit our Web site at http://www.niaid.nih.gov/dmid/genomes/. Press releases, fact sheets and other NIAID-related materials are available via the NIAID home page at http://www.niaid.nih.gov.

NIH/National Institute of Allergy and Infectious Diseases

Related Infectious Diseases Articles from Brightsurf:

Understanding the spread of infectious diseases
Physicists at M√ľnster University (Germany) have shown in model simulations that the COVID-19 infection rates decrease significantly through social distancing.

Forecasting elections with a model of infectious diseases
Election forecasting is an innately challenging endeavor, with results that can be difficult to interpret and may leave many questions unanswered after close races unfold.

COVID-19 a reminder of the challenge of emerging infectious diseases
The emergence and rapid increase in cases of coronavirus disease 2019 (COVID-19), a respiratory illness caused by a novel coronavirus, pose complex challenges to the global public health, research and medical communities, write federal scientists from NIH's National Institute of Allergy and Infectious Diseases (NIAID) and from the Centers for Disease Control and Prevention (CDC).

Certain antidepressants could provide treatment for multiple infectious diseases
Some antidepressants could potentially be used to treat a wide range of diseases caused by bacteria living within cells, according to work by researchers in the Virginia Commonwealth University School of Medicine and collaborators at other institutions.

Opioid epidemic is increasing rates of some infectious diseases
The US faces a public health crisis as the opioid epidemic fuels growing rates of certain infectious diseases, including HIV/AIDS, hepatitis, heart infections, and skin and soft tissue infections.

Infectious diseases could be diagnosed with smartphones in sub-Saharan Africa
A new Imperial-led review has outlined how health workers could use existing phones to predict and curb the spread of infectious diseases.

The Lancet Infectious Diseases: Experts warn of a surge in vector-borne diseases as humanitarian crisis in Venezuela worsens
The ongoing humanitarian crisis in Venezuela is accelerating the re-emergence of vector-borne diseases such as malaria, Chagas disease, dengue, and Zika virus, and threatens to jeopardize public health gains in the country over the past two decades, warn leading public health experts.

Glow-in-the-dark paper as a rapid test for infectious diseases
Researchers from Eindhoven University of Technology (The Netherlands) and Keio University (Japan) present a practicable and reliable way to test for infectious diseases.

Math shows how human behavior spreads infectious diseases
Mathematics can help public health workers better understand and influence human behaviors that lead to the spread of infectious disease, according to a study from the University of Waterloo.

Many Americans say infectious and emerging diseases in other countries will threaten the US
An overwhelming majority of Americans (95%) think infectious and emerging diseases facing other countries will pose a 'major' or 'minor' threat to the U.S. in the next few years, but more than half (61%) say they are confident the federal government can prevent a major infectious disease outbreak in the US, according to a new national public opinion survey commissioned by Research!America and the American Society for Microbiology.

Read More: Infectious Diseases News and Infectious Diseases Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.