A Classic View of Syphilis

So I was sitting here studying for my Tuesday final when I came across an interesting quote from The Breviary of Helthe (an infectious disease textbook written in 1547) describing syphilis:

"...In englyshe Morbus Gallicus [Syphilis] is named the french pockes, whan I was yonge they were named the spanyshe pockes the whyche be of many kyndes of pockes, some be moyst, some be waterashe, some be drye, and some be skorvie, some be lyke scabbes, some be lyke ring wormes, some be fistuled, some be festered, some be cankarus, some be lyke wenne, some be lyke biles, some be lyke knobbles or burres, and some be ulcerous havynge a lytle drye scabbe in the middle of the ulcerous skabbe, some hath ache in the jointes and no singe of the pockes yet it may be the pockes … The cause of these impediments or infyrmytes doth come many wayes, it maye come by lyenge in the shetes or bedde there where a pocky person hath the night before lyenin, it may come with lyenge with a pocky person, it maye come by syttenge on a draught or sege where as a pocky person did lately syt, it may come by drynkynge oft with a pocky person, but specially it is taken when a pocky person doth synne in letchery the one with another."

I guess I don't need to worry about syphilis because I doth not synne in letchery the one with another pocky person, nor doth I lyenge in the shetes or bedde there where a pocky person hath the night before lyenin. Hopefully syphilis doesn't come my way by syttenge on a draught or sege where a pocky person did lately syt!

... alright, back to studying for me. Focus Eric focus!

Salmonella and E.coli

Salmonella:

Get this - In 1996 1994 (thanks Kris for the fact check) 224,000 people in the united states were infected with Salmonella enteritidis after eating Schwan's ice cream (I'm glad I've never heard of that brand)! Why did this happen? Well, take note that Salmonella is commonly found on chickens (estimates reach nearly 80% for chickens infected with Salmonella, or Campylobacter), and that ice cream contains eggs. Now, Schwan's Ice cream making process, as far as eggs go, involves three factories:

1) an egg breaking plant: makes liquid egg
2) a processing plant: makes an ice cream pre-mix using the liquid egg from factory "1" and pasteurizes said mix.
3) The final Ice cream making plant: makes ice cream.

Unfortunately, in order to increase efficiency, Schwan's decided to use the same trucks that transported liquid egg from plant "1" to plant "2," to transport the pasteurized pre-mix from plant "2" to plant "3." Not a bad idea, but apparently nobody told the truck drivers to clean out their tankers before transporting the pre-mix, effectively nullifying pasteurization... DOH! From the New England Journal of Medicine, "Written procedures called for the washing of tanker trailers after the delivery of liquid eggs and specified that the interior of the tanker trailer was to be washed and sanitized and the outlet valve removed for hand cleaning plus sanitization before premix was loaded. Officials of the FDA and the Minnesota Department of Agriculture noted soiled outlet-valve gaskets, inadequate record keeping, and the lack of routine inspection of the interior of the tanker trailer." I guess that's how to get a quarter million people sick with dysentery.

E. coli:

Ever wonder why you should always get your burger "Well done?" E. Coli is present on the surface of meats, so when you cook a steak, in order to kill E. coli, you only really need to thoroughly cook the surface. The problem with ground beef is that you take that bacteria, originally just on the surface, and mix it all up inside the meat. So, don't eat pink burgers!

Jack in the Box learned this the hard way... A rare and particularly virulent form of E. coli (serotype O157:H7) happened to find it's way into their undercooked burgers, infecting 47 people. This is the same serotype of E. coli that caused the recent spinach scare. E. coli O157:H7 (a.k.a. EHEC for EnteroHemorrhagic E. Coli) is the main cause of Haemolytic-uremic syndrom, the main cause if kidney failure in children.

To see a cool video on how EHEC infects a cell go to: http://www.hhmi.org/biointeractive/disease/animations.html
scroll down and click on E. coli infection strategy. And while you're there, check out all the other cool videos about such topics as; Horizontal gene transfer "Bacterial conjugation" (as discussed in a previous post on antibiotic resistance), viral life cycle, recombination of viral genome, and HIV life cycle.

Santa Barbara Century Ride

See the route here: SB ride!

So here was the thought - Let's get 17 people from the triathlon team to ride from UCLA to Santa Barbara! We can rent out some wealthy person's guest house (thank you craigslist) and take the train back to L.A. (thank you amtrak)!

Well, we made it happen and oh what a success it was.

Now for some photos!

We applied sunscreen.











We fixed a flat tire whilst waving to Amtrak.








We laughed at the person who got a flat tire (Kelsey).








Some of us got very dirty (Kelsey again...).












And, we posed for numerous pictures... well most of us.

For more go to: Pictures!

Whooping Cough

Above: The characteristic "Coccobacillus" shape (stubby rods) of B. Perstussis

Pathogen: Bordetella pertussis (I guess pertussis means "violent cough")

A short history -

• 1906 - Jules Bordet and Octave Gengou are the first to cultivate B. pertussis. This is a very important step as in order to be prove an organism is the etiological cause of disease one must be able to isolate the bacterium in pure culture ( see Koch's postulates).
• 1930s - Development of a "whole-cell" vaccine. The first Bordetella vaccine was essentially killed B. pertussis bacteria. The dead cells were enough to illicit an immune response and cause activation and production of adaptive immune cells.
• 1947 - Childhood vaccination becomes routine. The DTP vaccine (Diphtheria, Tetanus, Pertussis) was very effective (90%).
• 1970s - Concerns about the vaccine arose. Common symptoms included redness, swelling, fever and pain (these are common with almost any vaccine). The main concern was a low frequency of seizures (1/100,00) that was associated but never proven to be caused by the vaccine.
• 1980s - Outbreak of pertussis in Great Britain where mothers were opting out of getting their children vaccinated.
• 1990s - A new vaccine is developed made of purified protein parts of B. pertussis. This vaccine undergoes several different permutations (Tripedia, Infanrix, Daptacel, Boostrix, and Adacel) reaching an efficacy level of 85%. Not quite as effective as original, but fewer side effects.

In the words of E.A. Mortimer, “Some people who go outside after a rainstorm and see frogs believe it rained frogs.” Unfortunately for many parents in Great Britain, the consequences of not vaccinating their children were much higher than the assumed risk of developing "vaccine related" complications. Many children likely died of the following Pertussis epidemic even though the vaccine was never proven to be the cause of any serious complications. Children weren'g vaccinated mainly because of a weak correlation with seizures. This historic example of the "correlation = causation" fallacy (For those who enjoy latin - cum hoc ergo propter hoc) reminds us to be careful about making such false conclusions. It makes sense to err on the side of caution, but it just so happens that the cautious side in this case was to immunize children from a highly virulent and communicable pathogen.

Botulism and Tetanus Toxins

Botox, the miraculous wrinkle eraser known for paralyzing faces of the rich and famous, turns out to be a toxin closely related to Tetanus neurotoxin, known for causing the less sought after "Lock Jaw"(warning: disturbing images).

Why is this interesting? Well botulism neurotoxin (Botox / BoNT) causes paralysis, but tetanus neurotoxin (TeTx) causes the exact opposite - over contraction of opposing muscles. Hmm... how does that work?

TeTx and BoNT are virulence factors released by the bacteria Clostridium tetani, and Clostridium botulinum respectively. As their names might suggest, both of these toxins attack neurons (hence neurotoxins). Now for the technical talk - how do these toxins do their thing?

Let's start with BoNT:

Getting into the neuron -
BoNT consists of two subunits, A and B. The B subunit attaches to a receptor on the membrane surface of the presynaptic neuron (the one that is sending the signal). Once attached, BoNT is endocytosed into the cell (basically it is in a little bubble inside the cell). The B subunit then creates a pore in the membrane of that bubble, allowing subunit A to enter the cell. BoNT is now in the cell and ready to do it's damage.

Doing Damage - Signals sent from neuron to neuron require a release of "neurotransmitters," or signalling proteins, into the synaptic cleft (the area between the presynaptic and postsynaptic neurons). These signalling proteins are made in the main body of the neuron, the soma, where RNA is translated into protein. They are then packaged into vessicles (kinda like the bubble mentioned earlier), and transported down the axon to the presynaptic terminal (where BoNT is). Normally, the vessicle would then dock with the cell membrane via "SNARE" proteins and release it's contents into the synaptic cleft where they could signal the postsynaptic neuron to propagate the signal. BoNT basically cut's up certain "SNARE" proteins, preventing vesicles from being able to dock and release their transmitters. No SNARE --> No docking --> No release of transmitter --> No propagation of signal --> paralysis!

Now for TeTx:
TeTx works in pretty much the exact same way except for it chews up SNAREs that are present in inhibitory neurons. Inhibitory neurons function to relax the opposing muscle of the muscle that is being signaled to contract. So, in the case of the jaw, both the muscle that closes the jaw and the muscle the opens the jaw are simultaneously contracting. The reason your jaw locks shut when this happens is that the muscles that close your jaw are much stronger than the muscles that open.

There you have it! Two toxins that do essentially the same thing, but with drastically different results.

Now for a few cool facts:

• 1 gram of crystallin BoNT could kill more than 10,000 adults
• Babies shouldn't eat honey because honey often contains botulinium spores found in the wild. Botulinium spores are not a problem for adults because we have a mature intestinal flora (lots of bacteria that outcompete the botulinium spores allowing them to pass through our system without germinating and colonizing)
• Both of these bacteria are anaerobic (meaning they grow in conditions without oxygen). Rusty nails happen to have rough surfaces allowing for exclusion of oxygen, so rusty nails happen to be a good location for bacteria like tetanus to grow. Tetanus has nothing to do with rust, it just happens that rusty nails allow for a good environment for the bacteria to grow, and a way for the bacteria to be transmitted into humans (don't step on that rusty nail!).

That's all for now!

Staphylococcus aureus and Antibiotic Resistance

Does MRSA ring a bell? Yeah, Methicillin-Resistant Staphylococcus Aureus, known for causing nasty infections in hospitals around the country. Well, If you ever wanted to know where MRSA may have developed it's methicillin resistance, read the following:

Bacteria Subsisting on Antibiotics (The full article is no longer freely available. This link will take you to the free abstract.)

So, an "antibiotic resistome" eh? My favorite line, "We cultured clonal bacterial isolates from 11 diverse soils (table S2) that were capable of using one of 18 different antibiotics as their sole carbon source." Wow! Not only were bacteria found to be merely resistant to antibiotics, they were found to be using them as their SOLE energy source! That's what I call specialization!

The relatively recent development of antibiotic resistance in strains of Staph might lead one to wonder, considering the relatively little time humans have been using antibiotics in medicine, how have bacteria been able to adapt so quickly to our treatments to become so resistant in only a matter of decades? Though bacteria do reproduce quickly allowing for accelerated evolution, random mutations seem like an unlikely culprit for how fast Staph has been able to adapt to our treatments. Then how did it happen? One possible answer is in this paper. The problem is thinking in such a human centric manner. Ultimately, resistance mechanisms did have to evolve at some point in time, but these resistance genes did not likely evolve in the past hundred years.

Think about where we got our first antibiotics - from fungi, molds, plants! Bacteria have been evolving alongside all of these hosts for far more than thousands of years. So, how did Staph, a human pathogen, manage to get the resistance gene from a bacteria that colonizes on fungi? Horizontal Gene Transfer (HGT). Hence, the concept of the "antibiotic resistome," an environmental reservoir of antibiotic resistance. From this reservoir, bacteria can essentially share genes that they have evolved through co-evolution with another species of bacteria.

Put simply, bacteria can share certain defenses. Staph can pick up what it needs to survive our "advanced" treatments by just picking up the defenses another species of bacteria has used to survive these antibiotics for thousands of years.

Anyhow... I thought that was interesting.

"...enabling same-sex couples to have their own genetic offspring."

A must read article from Nature...

New Sources of Sex Cells

A little background for those who might need it - so, some scientists set out to determine the differences between pluripotent cells (stem cells, a.k.a. cool cells that can differentiate into any type of tissue) and differentiated cells (like a skin cell). Turns out that if you transfect (insert genes via a virus) 4 specific genes into a differentiated cell you can "induce pluripotency" to form an induced pluripotent stem (iPS) cell. In other words, you can make what looks and acts like a stem cell from almost any cell... woah. They did this in 2006 with mice cells and then again in 2007 with human cells.

Two important notes -

1. Though iPS cells have a gene expression profile that is very similar to embryonic stem cells, they are NOT exactly the same. So, there is some concern that these cells might not differentiate in an expected manner, or may become cancerous (freaky mutant petri dish babies!!!!!), and so on.

2. The current method of gene introduction, transfection, is known to cause some problems (this is why they stopped gene therapy experiments). The problem is achieving site-specific integration of those 4 special genes. If one of those genes happens to, say, integrate into a tumor suppressor gene, thus knocking out that gene, voila! you have a potentially cancerous cell. hmmm... problems. Well, needless to say, scientists have been working on developing new techniques of gene introduction (some completely new and some just special forms of transfection) and I have been told by one of my professors that "the near future looks promising."

So, obviously there are some interesting ethical discussions to be had... Perhaps another time. I need to get some sleep.

[Important note: I am not an expert on this field. In fact, I haven't even finished my B.S., so if I have any details wrong, which is probably the case, please feel free to enlighten me.]