Thanks to All the Little Genomes

By M.L. Baker  |  Posted 2005-03-07

Thanks to All the Little Genomes

Yes, the Human Genome Project is impressive, but our self-centered fixation is causing us to overlook genetic work that could be just as important—and yield rewards far sooner.

The top 50 human pathogens have all been sequenced. Malaria, tuberculosis, typhus and your ilk, weve got your number. Actually, better yet, weve got your genomes.

Those who think this is only good news for the developing world should remember that the research community was shocked to learn bacteria cause stomach ulcers, and that infections are suspected in heart disease, atherosclerosis, cancer and even some psychoses.

But its not the genomes themselves that will spark ideas for fighting disease. Nowadays, applications of genomics owe more to computational tools (bioinformatics) than to the sequencing machines that actually read out the As, Gs, Ts and Cs.

Even the head of one of the worlds leading sequencers says so. "Bioinformatics is an enabling technology," said Claire Fraser, president of TIGR (The Institute for Genomic Research); "DNA sequencing would be of little value without it."

Read more here about the developing standards for bioinformatics.

Bioinformatics turns a string of letters into useful information. Though the technology isnt perfect, it means computers can hunt through gene sequences and make broad guesses as to what they do.

Does the protein made from the gene stay inside the cell to keep its innards running smoothly? Is it, like insulin or growth hormone, pumped out of the cell to trigger action elsewhere? Or perhaps the protein lodges in the cell membrane to detect whats happening outside and tell the cell how to adapt?

With sequences of related bacteria, bioinformaticians can figure out what genes make one bacteria harmless and another dangerous. Or what makes one bacteria unable to infect humans while its cousin wreaks havoc in our organs.

As powerful as antibiotics are, our armory is limited, and shrinking with antibiotic resistance. The thirty or so marketed antibiotics fall into just three classes, Fraser told attendees at a scientific conference last month. They either disrupt cell walls, muck up DNA replication and repair, or keep a pathogen from making the proteins it needs. But sorting through the genomes reveals all sorts of other ways to attack infectious disease.

To some of you, the last sentence sounds awfully familiar. In the 1990s, biotech stocks skyrocketed in anticipation of the medical windfall from the human genome sequence. That has been slow in coming, but their counterparts are arriving for infectious disease, which have less than a tenth the number of genes we do.

A leading medical journal called for genomic data on pathogens to remain widely available, saying the benefits of promoting medical research far outweigh the risks of helping bioterrorists. Click here to read more.

Researchers can find the genes that code for how a pathogen interacts with human cells, or look for drugs that can knock off problematic bacteria without attacking the helpful ones in your gut.

But the most promising developments may be the technologies use for designing vaccines in silico.

First, bacterial genes are analyzed by a computer to find ones that make proteins that are located where the human immune system can detect them, like those on the bacterias cell wall. Next, lab experiments determine which are likely to prompt an appropriate immune response.

Using this approach, researchers working together at Chiron and TIGR discovered five new experimental vaccines for meningitis. These moved from idea to human trials in just two years, a pretty speedy pace for vaccine development.

With the sequences in hand, such an approach to vaccine-making can become routine, predicted Fraser.

Next Page: Non-viral pathogens that infect humans.


-Viral Pathogens That Infect Humans">

For an idea of what researchers have to work with, the list of sequenced non-viral pathogens that infect humans, along with closely related pathogens, is below. Of course, along with the chicken, chimpanzee, dog, rice and other well-known organisms, many microscopic ones have been sequenced. The complete list includes many bacteria that infect plants as well as many bacteria useful for food, manufacturing and health.

Bacillus anthracis (causes anthrax, nine strains sequenced)

Bacillus cereus (causes food poisoning, four strains sequenced)

Bacillus subtilis (relative of the bacteria that causes pneumonia)

Bacteroides fragilis (normally lives harmlessly in the gut, but can cause fatal infection if it escapes into the body)

Bartonella henselae (causes cat-scratch disease)

Bartonella quintana (causes trench fever, characterized by fatigue and a rash)

Bordetella bronchiseptica (causes respiratory problems)

Bordetella parapertussis (relative of bacteria that causes whooping cough)

Bordetella pertussis (causes whooping cough)

Borrelia burgdorferi (causes Lyme disease)

Brucella melitensis (causes Malta fever)

Brucella suis (causes flu-like disease)

Burkholderia mallei (causes glanders, used as a bioweapon in the Civil War)

Burkholderia pseudomallei (causes meliodosis)

Campylobacter jejuni (major cause of food poisoning)

Candida glabrata (a yeast that causes yeast infections)

Chlamydia muridarum (relative of bacteria that causes chlamydia)

Chlamydia trachomatis (causes chlamydia, which can lead to infertility)

Chlamydophila caviae (related to a bacteria that can cause blindness)

Chlamydophila pneumoniae (causes pneuomonia and bronchitis)

Clostridium perfringens (causes food poisoning)

Corynebacterium diphtheriae (causes diptheria)

Coxiella burnetii (causes Q fever)

Cryptosporidium hominis (a parasite that causes diarrhea)

Cryptosporidium parvum (a parasite that causes diarrhea, sometimes spread in swimming pools)

Encephalitozoon cuniculi (a parasite that causes diarrhea, pneumonia and bronchitis)

Enterococcus faecalis (normal a peaceful resident of the gut, can infect wounds and the urinary tract)

Escherichia coli (though most strains are harmless, some can cause food poisoning or other disease, four strains sequenced)

Fusobacterium nucleatum (infects liver, neck, chest and lung, associated with gum disease)

Haemophilus ducreyi (causes ulcers, may help transmit HIV)

Haemophilus influenzae (not to be confused with the flu virus, this bacteria causes respiratory and ear infections and was the first organism to be sequenced)

Helicobacter hepaticus (relative to bacteria causing ulcers)

Helicobacter pylori (leading cause of stomach ulcers, can cause stomach cancer)

Legionella pneumophila (causes a form of pneumonia, Legionnaires disease)

Leptospira interrogans (causes leptospirosis)

Listeria monocytogenes (causes listeriosis)

Mycobacterium bovis (relative of bacteria causing tubercolosis, infects cattle)

Mycobacterium leprae (causes leprosy)

Mycobacterium tuberculosis (causes tubercolosis)

Mycoplasma genitalium (causes infections of humans reproductive tracts)

Mycoplasma mycoides (causes infections of cattles reproductive tracts)

Mycoplasma penetrans (causes infections of the urogenital and respiratory tracts)

Mycoplasma pneumoniae (causes a pneumonia-like disease)

Mycoplasma pulmonis (causes respiratory infections in rodents)

Neisseria meningitidis (causes meningitis)

Nocardia farcinica (causes potentially fatal lung or nerve infection)

Pasteurella multocida (causes cholera in birds and infectious arthritis in humans)

Plasmodium falciparum (this parasite causes malaria)

Plasmodium yoelii yoelii (this parasite causes malaria in rodents)

Porphyromonas gingivalis (causes gum disease)

Propionibacterium acnes (causes pimples and, perhaps, corneal ulcers and gallstones)

Protochlamydia amoebophila (relative to bacteria that cause pneumonia and venereal disease)

Pseudomonas aeruginosa (can cause fatal lung infections in people with cystic fibrosis)

Rickettsia conorii (causes spotted fever)

Rickettsia typhi (causes a milder form of typhus)

Rickettsia prowazekii (causes typhus, responsible for millions of deaths)

Rickettsia sibirica (causes North Asian tick fever)

Salmonella enterica (causes typhoid fever)

Salmonella typhimurium (causes gastrointestinal disease)

Shigella flexneria (causes severe diarrhea, leading to many infant deaths in developing countries)

Staphylococcus epidermidis (normally harmless, can infect wounds)

Streptococcus agalactiae (known as group B strep, causes life-threatening infections)

Streptococcus mutans (causes much tooth decay)

Streptococcus pyogenes (known as group A strep, causes Strep throat, toxic shock syndrome and rheumatic fever)

Treponema denticola (causes gum disease)

Tropheryma whipplei (causes Whipple disease)

Ureaplasma urealyticum (infects the urinary tract)

Vibrio cholerae (causes cholera)

Vibrio parahaemolyticus (causes gatrointestinal disease)

Vibrio vulnificus (relative of bacteria that causes cholera)

Yersinia pestis (causes plague)

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