Microcosm by Carl Zimmer

Microcosm: E. coli and the New Science of Life by Carl Zimmer

Discovery
Escherichia coli bacteria was discovered by the German-Austrian pediatrician Theodor Escherich. He found it in baby diapers.

Beneficial Bacteria
E. coli inhabit the human colon and most strains of E. coli are beneficial, not pathogens. In fact, most of the bacteria in your colon are non-pathogenic. When you take antibiotics to kill pathogenic bacteria, the antibiotics often also kill friendly bacteria, resulting in diarrhea.

Cadaverine
E. coli bacteria in the intestines neutralize acid by producing an alkaline, foul-smelling substance called cadaverine.

Iron
E. coli makes proteins called siderophores that grab iron atoms in the environment and move it inside the E. coli bacterium, where it is held by an iron storage protein until it is needed by the cell.

Biofilm
Biofilm is an extracellular matrix, largely made up of polysaccharide mucus, that helps the E. coli bacteria to cooperate to promote their group survival. It protects the bacteria from antibiotics, predators, and dehydration.

Evolutionary Cooperation
The author discusses recent theories of evolution that assert that natural selection favors not just traits that help an individual organism survive, but also traits that help the survival of their close genetic relatives, from its immediate family to its species. An E. coli bacterium will often perform acts that harm itself, but help neighboring E. coli bacteria survive, by improving their shared environment.

Oxygen
The E. coli bacteria in the gut are called facultative anaerobes, which means that they can live in either the presence or the absence of oxygen. The E. coli bacteria scavenge oxygen in the gut to maintain the colon in an anaerobic state. This makes the colon hospitable for anaerobic microbes.

Regulation of Heat-Shock Proteins
E. coli produces proteins called heat-shock proteins that help the bacterium to handle proteins that have been partially denatured (unfolded) by heat. There are two kinds of such helpers: (a) ones that help repair (refold) the damaged proteins, and (b) ones that help destroy the proteins which cannot be repaired. The level of production of these heat-shock proteins is regulated in an interesting way. The messenger RNA for the sigma 32 regulatory protein assumes a functional shape for transcription on the ribosome only when bacterium is hot. After the sigma 32 protein is synthesized, it turns on the transcription of the genes for the heat-shock proteins. There is also a feedback loop where excessive amounts of heat-shock protein will shut down their production.

Colicin
E. coli produce toxic proteins called colicins that kill neighboring bacteria of other species. The colicins have three mechanisms of action. Some colicins form pores in the membranes of the enemy bacteria, some prevent protein synthesis, and some attack DNA. E. coli also produce other proteins, called immunity proteins, that protect them from harm by their own colicins.

Type III Secretion System
This is a needle-like structure on the outside membrane of E. coli cells that allows them to inject toxins into the host cell.

Flagella

E. coli have complex structures on their outer membranes called flagella that help them move. Flagella evolved from the more primitive structure described above, the Type III secretion system.

Prophage
A virus that attacks (eats) bacteria is called a bacteriophage (or just phage, for short). If the DNA of the virus integrates into the host chromosome, that DNA segment is called a prophage. It can be passed down to the descendants of the bacterium, and sometimes can cause a viral infection in the descendent bacteria. Many prophages develop mutations that prevent them from ever escaping the host chromosome back into a virus capsid. They are called defective prophages.

Shigella
This form of diarrhea was discovered by Kiyoshi Shiga. Only recently was it discovered that the shigella bacterium is actually a group of strains of E. coli that have developed the ability to move around inside eukaryotic cells. The Shigella bacterium spreads from host cell to cell by loosening the tri-cellular tight junction of intestinal epithelial cells. The Shiga toxin attacks the RNA part of the bacterial ribosomes, halting protein synthesis. Shiga toxin is encoded by a gene in a lambdoid prophage integrated into the bacterial chromosome. These shigella strains also differ from normal E. coli in that they do not have flagella and do not produce cadaverine.

E. coli Strain O157:H7
The pathogenic O157:H7 strain of E. coli occasionally found in undercooked, contaminated ground beef produces a shiga-like protein toxin that is coded for by a defective prophage gene.

Riboswitch Sensors
Recently, it has been discovered that the synthesis of vitamin B12 (cobalamin) by E. coli is regulated in a novel way. This regulatory mechanism involves the messenger RNAs that code for coenzyme B12 biosynthesis and transport proteins. When vitamin B12 binds to a nucleotide sequence of such a messenger RNA, the mRNA changes its shape. In this new conformation, the mRNA will no longer bind to the ribosome and so will not be translated into a biosynthesis or transport protein for vitamin B12. Ron Breaker of Yale University gave the name riboswitch to the nucleotide sequence of the mRNA that binds the vitamin molecule.

RNA World
Starting in 1968, a number of scientists have speculated that the earliest life on earth consisted not of DNA and proteins, but rather of RNA only. These RNA molecules acted as both holders of genetic information (like DNA) and as performers of chemical reactions (like proteins). In the 1980s there were discoveries supporting this theory. It was discovered that there are RNA molecules that act as enzymes, that is, they catalyze chemical reactions. They are called ribozymes. More recently, French virologist Patrick Forterre has proposed the theory that the switchover from RNA-based life to DNA-based life happened independently for each of the three domains: archaea, bacteria, and eukaryote. He has further proposed that the DNA of cells was first introduced by DNA viruses.

Genetically Modified Organisms (GMO)
The author is an advocate of genetic engineering, which started with E. coli, but which has now spread to higher forms of life. He goes into some detail on a particular plant GMO called “Golden Rice”. Golden Rice was developed by Ingo Potrykos of the Swiss Federal Institute of Technology and Peter Beyer of the University of Freiburg. This rice GMO makes vitamin A, which is needed for vision. Millions of poor children go blind every year, because do not eat enough vitamin A.

Viruses vs. Superbugs: A Solution to the Antibiotics Crisis? by Thomas Häusler

Antibiotic Resistant Bacteria:
We are in trouble because many common pathogenic bacteria have become resistant to antibiotics. Because of bacterial resistance to antibiotics, many patients end up with chronic infections and limbs that need to be amputated. Boils and carbuncles are caused by staphylococcal bacteria on the skin. Pseudomonas aeruginosa often infects burn wounds. Clostridium difficile causes intestinal infections in hospitals. One bacteria studied was Clostridium, which causes gas gangrene. People lost interest in the phage treatment for typhoid fever when the antibiotic chloramphenicol became available in 1947. In India, many typhoid fever infections have become resistant to chloramphenicol. Antibiotics often fail for bone infections, due to poor circulation. Antibiotics kill beneficial bacteria, also.

Viruses That Eat Bacteria:
A novel solution to this problem is to use bacteriophages. Bacteriophages kill bacteria. Phages kill only bacteria, not plant or animal cells. They are specific. Each strain of phage kills only a particular strain of bacteria. They are more specific than antibiotics. Bacteria mutate or receive plasmids that make them resistant to a particular phage, but that phage can evolve so that it can continue killing that strain of bacteria. Hospital sewage is a good place to look for bacteriophages that attack hospital bacteria. Untreated city sewage are also a good place to look for phages. During World War II, Canadian and American scientists studied using phages to treat typhoid fever, with is caused by Salmonella typhi. Using bacteriophages to treat infection was considered during the early years of molecular biology, but abandoned by most researchers when antibiotics came along, so phages no longer seemed necessary.

Pasteur Institute:
Much of the early science was done by French scientist Félix d’Herelle worked at the Pasteur Institute during World War I
d’Herelle investigated the use of bacteriophage against:
• the Shigella bacteria that cause dysentery (a major problem in the trenches)
• the Salmonella bacteria that infect chickens
• the Vibrio cholerae bacteria that causes cholera (major study in India)

Eliava Institute in Tbilisi Georgia:
Georgiy Georgievitch Eliava studied with d”herelle at the Pasteur Institute in Paris. Later, Eliava brought Félix d’Herelle to Tbilisi. The Institute for Microbiology in Tbilisi was founded in 1923 with Eliava as scientific director. It appears that Eliava may have come to the attention Lavrenti Beria. Eliava disappeared in 1937. Eliava’s stepdaughter Hanna was deported to a camp in Kazakhstan. After the breakup of the Soviet Union, the phage research institute in Georgia has fallen on hard times.

Scientific Rigor:
Early research on the medical use of bacteriophages failed to adhere to the modern standard of scientific rigor. After World War II, Rene Dubos studied the treatment of mouse dysentery with phage in a rigorously scientific way. In order to prove definitively that phages are a good treatment, hundreds of millions of dollars of more research is required. The expense to perform clinic studies to obtain FDA approval for drugs for humans is so great, that much phage research is now being directed towards veterinary products.

Biotech:
In recent years, a number of biotech companies have pursued phage therapeutics:
• Gangagen Biotechnologies of Bangalore (half-bacterial-half-viral hybrid protein to fight staph infections)
• Intralytix (who product ListShield™ is used to kill Listeria monocytogenes on seafood)
• OmniLytics (producer of AgriPhage, a pesticide for bacterial stem canker in tomato plants)
• Viridax (developing phage therapies for staphylococcus aureus respiratory infections)

Soviet Georgia:
The most fascinating item in the book does not concern bacteriophages at all. It is a memoir by a Georgian that states that during Stalin’s reign of terror in the 1930s, members of cinema audiences were afraid to be the first one to stop clapping when Stalin’s photograph was shown, because it might lead to an arrest by the secret police.

Parasite Rex by Carl Zimmer

Parasite Rex: Inside the Bizarre World of Nature’s Most Dangerous Creatures by Carl Zimmer

Trypanosomes

Trypanosomes are one-celled eukaryotes (not bacteria or viruses) that are spread by the tsetse fly and cause sleeping sickness in humans. They also infect cattle, making it difficult to raise cattle in many parts of sub-Saharan Africa. When Western colonists, ignorant of this fact, forced the Africans to raise cattle in areas with tsetse flies, they caused epidemics which killed millions of Africans. The parasite damages the part of the brain that regulates the sleep cycle.

Immunoglobulin E

One type of antibody, called immunoglobulin E, is specialized to fight parasites. It coats the insides of the intestines to prevent the entry of parasites. With an absence of parasites in modern, hygienic society, the immunoglobulin E has nothing to do, so it has latched around for something else to attack. This is where allergies come from. Ulcerative colitis and Crohn’s disease are common only in societies with good sanitation and few people with parasitic intestinal worms. Some scientists are experimenting with using parasitic worms to treat inflammatory bowel disease.

Elephantiaisis

The author interviewed parasitologist Michael Sukhdeo of Rutgers University. Sukhedo himself has suffered from parasitic disease. When he was 11 years old in British Guyana, he contracted elephantiasis. The disease is caused by thread-like worms that reside in the lymph glands and cause swelling. The worms are transmitted by the mosquito.

Cook Your Pork Well

The nematode Trichinella spirals causes the disease Trichinosis, which is acquired by eating undercooked pork. The nematode mates in the cells of the lining of the intestines. Baby nematodes travel through the bloodstream to the muscle cells. The liver fluke Fasciola hepatica infects many cattle in tropical countries. Sukhdeo discovered how they migrate from the intestines to the liver. They crawl to the top of the abdominal cavity, where the diaphragm meets the liver, then enter the liver.

Blood Fluke

The blood fluke causes the disease schistosomaiasis, also called bilharzia and snail fever. It lives in water snails. The flukes drill their way through human skin to get into the bloodstream. The male and female slukes meet in the human liver and mate. Looking schistosomiasis up in Wikipedia I discovered that civil engineers in Africa unwittingly contributed to the spread of these blood flukes, because they were ignorant of the fact that when they build irrigation systems, they had to keep the water moving above a certain speed, to prevent the snails from attaching themselves to the sides.

Sex

Sexual reproduction creates a diversity of hosts within a species that is difficult for the parasite to adapt to. In fact, sexual reproduction may have involved largely as a defense mechanism against parasites.