parasitic strategies - loooong

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<pennyhoule@y...> wrote:

> Okay, doesn't this last paragraph seem kind of significant?

> Actually, kind of huge???

>

> " Five of the Missouri isolates were obtained from the Dowd farm

which

> is the site of a human patient with a classical erythema migrans

(EM)

> lesion and clinically diagnosed with LD. Interestingly, however,

> preliminary experiments involving needle injection of 2 of the

> isolates into mice failed to infect the mice. "

>

> Why would injecting the isolates not infect the mice? Does this

mean

> we're dealing with an immune system problem first, not a contagion

> problem?

In short, no. (No as in " not necessarily " .) Many bacteria are able to

infect only certain mammals. I am familiar with many examples of this

phenomenon but not with work delving into the reasons (which must be

considered extremely fascinating from a long-term therapy-development

perspective).

Actually I am gonna have to pull back from that a bit, because I am

learning more every month about benign (asymptomatic) bacterial

infections of mammals. We dont know yet if this benignity comes

mostly from low bacterial numbers or from a " bad " host reaction.

Therefore the failure of Treponema pallidum (syphilis) and

Mycobacterium leprae (leprosy) to cause disease in the mouse doesnt

altogether prove that mice cant have the same sort of infections with

these organisms (but without disease) as humans have when they are

diseased by the same organisms. (This is especially so because late

syphilis and many cases of leprosy are small-biomass infections, at

least according to observations *so far*, which is why these diseases

are often " blamed " on the host immunity.) However, it still appears

likely that Tp and M leprae simply cant survive in the mouse at all.

Anyways, I think there are probably examples of large-biomass

infections which fail to thrive in certain mammals.

But of course, we *could* be dealing with an immune system problem.

This could be an immunodeficiency allowing borrelia to persist - but

in light of the data on how well borrelia infects so many mammals,

almost always asymptomatically or nearly so, I would be more tempted

to conclude that the immune system problem is one of hyperreactivity

to an organism that ought to be tolerated.

Still, my personal favorite " guess " is that none of those scenarios

is true. Heres a bit of speculation - bear in mind I am just blowing

off steam, because I havent read what anyone has to say on these

topics:

Divide microparasites into two classes - obligate and free. An

obligate parasite *has* to have a specific living host, but a free

organism is nonspecialized, and when its not eating you its eating

dead leaves in the woods, algae, or your dead skin cells (on the

outside of your skin), or living in your bowel, or whatever. I think

Vibrio cholerae and Mycobacterium leprae are like this; they can live

in the environment. And of course things like Staph epidermis and E

coli live with you, but 99% of the time, stay on the exterior of the

body proper (this includes the lumen of the GI, its not

really " inside " you).

To, say, Bacillus anthracis (anthrax), youre just one more thing to

exploit. Youre like a rotting log that it can sink its teeth into.

You have a nasty immune system for it to deal with, but at least you

arent full of hostile fungi like a rotting log is. Whether you die or

whatever is no big deal to it. In fact, things are simpler for it if

you do die, which is one reason for its spewing this totally

incredble macrophage-shredding toxin that is so often lethal to

infected humans. Once anthrax devours you it will just go back to

eating leaves, having multiplied extensively.

An obligate parasite cant do that; it has to spread to other hosts.

If its going to kill you, it needs to also get out of you and into

your mammal brethren, or else there was no point getting into you in

the first place (which doesnt mean such things dont happen anyway -

everything that persists in nature does have a purpose, but of course

not all of nature persists - therefore not all of what we see

happening in nature right now necessarily has a purpose).

Because of its dependance, what advantages a specialised obligate

parasite is much more subtle and complex than what advantages a free

parasite that is taking opportunistic advantage of you. An obligate

parasite needs you and needs to take your needs into account.

Some obligate pathogens, like smallpox virus, seem to usually kill

the host. They do not leave any fodder for their progeny. Thats why

they have to bounce around the earth in waves; if they stopped moving

theyd become extinct. Thier strategy presumably requires that they

always be extremely well-adapted to savage a host (this is where Im

starting to " make stuff up " provisionally because I dont really know

if any germs of this stripe have chronic benign persister states like

EBV etc do). They must seize have every advantage in exploiting the

host and opposing immunity. In many or most cases they may want to be

thru with you within several days, before the powerful adaptive

branch of the mammalian immune system can even mobilize. The price

is, again, geographical nomadism, because hosts get devastated.

Something like EBV and Bb has a whole different angle. It wants to

stay with you. Forever. And all your mammal buddies too. Look at

these data for Missouri, things like 65% of assorted mammal species

carrying Bb. How are EBV and Bb so successful at evading immunity? Bb

has very few exposed proteins, according to Radolf, and its exposed

lipids are probably not immunogenic, again according to Radolf. This

makes Bb (and Tp even moreso) able to avoid the immune systems

scrutiny to a high degree. (The cost to them may be that they grow

very slowly, because with few exposed proteins they are not able to

pump many nutrients into themselves. Hence the 36h and 12h ideal

generation times of Tp and Bb are no shock.)

When Bb is do damn good at what it does (so good that it infects 65%

to virtually 100% of wild possums or mice or whatever), it doesnt

want to kill them. Where would it be then? Heck, it doesnt even want

to make them sick. Healthy mice are good, they bring home the bacon,

of which Bb can appropriate its share. An " endurance " pathogen has

absolutely no interest in savaging a population, moving on to the

next continent, and waiting 20 years to come back again. Bb is so

good at avoiding immunity that it doesnt need to " win " against the

mammal, like smallpox does, in order to reproduce at all. The Goths

or whoever wouldnt have sacked Rome if theyd had some stable way of

leaching off of it long-term.

When syphilis first reached Europe circa 1500, it is said to have

been an extremely lethal infection. Within a few years it learned to

treat its new hosts more gently, helping it to spread much more

rapidly.

The larger percentage of a mouse population Bb infects, the greater

the incentive for Bb not to harm the mice *at all* if possible. One

good way for it to do that is to infect each mouse in very small

numbers. HOWEVER, the key is to realize the counterpressure here. Bb

doesnt just need to survive, it needs to be transmitted (presumably

this happens mainly via tick in mice, but perhaps also sexually and

congenitally). It is going to be much more likely to be transmitted

from a mouse if it is present in HIGHER numbers, even if this does

risk making the mouse a little sick.

So, these forces are in opposition. For strain X of Bb, there might

usually be 10^8 bacteria per mammal, and for strain Y, 10^12, which

is 10,000x more. Say there are 10 unicorns infected with strain Y;

they have so many bacteria that five of them might get sick and die,

which is too bad for strain Y. But if there are 10 ticks feeding on a

unicorn that has strain X, 5 of them might not ingest enough borrelia

to become infected, which is too bad for strain X.

Moreover, if strain X is in a unicorn, arousing little immune

response, and then strain Y comes along and infects the same unicorn,

there is going to be a larger immune response against epitopes that

both strains have. Now under these new circumstances there might end

up being only 10^6 organisms of strain X, so X is unlikely to be

transmitted to ticks biting this unicorn, and its strategy of

being " nicer " to the host makes it a loser in this particular

scenario.

Therefore, these opposing forces keep things in balance.

In something like H pylori, you see different strategies

simultaneously just like this, at least according to my soft reading.

A huge percentage of people have Hp, and most of them are A-OK for

all we know. Only a few people have the pathogenic Hp strain; this

one is more aggressive. It presumably(?) is less likely to be

eradicated by the host and more likely to spread, the cost being that

it harms the hosts to a degree and therefore ultimately harms itself

proportionally.

At any rate, what a " permanent " parasite CANT afford, above all, is

to be eradicated. I think it may be that one of Bb's anti-eradication

strategies may find itself unopposed by the peculiar immunity of the

human, and therefore Bb multiplies more successfuly than it " planned "

to, causing illness. Who knows tho. Speculation only gets you so far,

because as I said, the acts of organisms have no purpose, unless they

turn out to, which is only the case if the organisms survive. Bb

therefore doesnt necessarily have to benefit from infecting humans -

it can just do it anyway. Only more microscope work can tell us what

the hells going on. I have a paper from the 80s in which the authors

state that they knew of ZERO electron microscopy of tissues of

tertiary syphilis. Its a black hole.

> Does anybody know if IGENEX has done any trials with healthy

> patients as controls? Do we know whether the same number of healthy

> people tested positive on their tests? (I remember a friend telling

> me that the founder of Igenex told her something along these lines).

I am not aware that they have published anything. However I just

looked up Dr in pubmed and found this published comment, which

I lack access to right now: PMID 11690582.

There is (or was last fall) an assertion at the site that they used

negative controls in setting their sensitivity/specificity standards.

Many assays for this or that have a US national standard for

processing and interpretation, but this is *not the case* for the Bb

WB. When you see studies involving Bb WB, they are just doin their

own thing, and you dont know for sure how it would compare with

somebody elses WB.

> That would mean the question is why can't some of us recover from

> these organisms? Or why do we get overwhelmed by them when others

> don't? It's the same with staph. Everyone carries staph. But why do

> we have billions times more of the critters than other people?

> That's why even though I'm sick, I don't make other people sick,

> unless they are also predisposed or some how exposed to the same

> conditions I have making us more susceptible.

>

> penny

>

>

>

> > This is a crosspost from lymenet. Wherever its from, its not in

> > pubmed yet. Whole text from lymenet is below, but I'll spare ya

> the

> > suspense:

> >

> > " Western blots are being conducted to confirm positive ELISA

> results.

> > Rabbits, deer, white-footed mice, cotton mice, and deer all show

a

> > prevalence of 65% or more positive for presence of IgG antibodies

> to

> > the MOD-1 Bb isolate. "

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