journal club: why virulence??
coker at usuhs.usuhs.mil
coker at usuhs.usuhs.mil
Fri Aug 12 13:18:21 EST 1994
In Article <32arp4$enb at mserv1.dl.ac.uk>
mbpln at s-crim1.dl.ac.uk (M.J. Pallen) writes:
>HYPOTHESIS FOUR:Virulence is short-sighted
>The really interesting part of Levin & Bull's paper is their new idea
>of "short-sighted virulence". What they mean by this is, to quote
> "virulence evolves within the micro-environment of individual
>hosts, without regard for the ultimate 'survival' (transmission) of
>the population of hosts. In this model, the virulence of a pathogen
>is analogous to that of a clone of neoplastic somatic cells, which are
>the product of mutation and selection within a 'host'".
>This strikes me as a fascinating idea. Levin & Bull posit that their
>model of short-sighted virulence requires that mutants arise in host
>tissues which have increased fitness in those tissues, as compared to
>the ancestral, transmissible, population--the micro-organisms that
>are actually responsible for virulence belong to a quite distinct
>population, that is _not_ transmitted from host to host.
>They cite three possible examples--bacterial meningitis, paralytic
>poliomyelitis and AIDS. The example of bacterial meningitis seems
>particularly apt--what possible advantage, in terms of
>transmissibility, does invasion of the brain bring to pneumococci,
>meningococci and Haemophilus influenzae? One might posit the co-
>incidental evolution idea here again, i.e. the virulence factors
>involved in pneumococcal or haemophilus meningitis may have
>evolved to cause the adaptive conditions, pneumonia or epiglottitis
>(adaptive in the sense of aiding transmission). However, Levin &
>Bull quote evidence suggesting that mutations are required before
>these pathogens can cause invasive disease.
>This leads on to the important point of testability. Anyone can put
>forward a nice hypothesis, but Levin & Bull go beyond this to
>discuss the experimental evidence that already exists in support of
>their hypothesis and to suggest ways in which their idea might be
>put to more conclusive tests.
It seems to me since many virulence traits of bacterial pathogens are
multifactoral a number of "mutational events" would have had to occur that
would give rise to the virulence phenotype. In considering a stepwise
accumulation of virulence gene determinants a number of continuous hosts would
have to be involved. (Other models? for example transfer of a group of
"invasion" genes via plasmids-but how did these genes arise and how
did they become linked?)
For example, in the Yersinia model of cellular infection of humans, I would
think that the Yersinia progenote would have had to mutate in such a fashion
that the bacteria would acquire a trait for attachment to eucaryotic cells.
Then mutate to induce uptake, then mutate to evade internal host cell
responses, etc. (or a variation of the above). It is clear that several
distinct genetic loci are involved in these processes thus indicating that
several mutational events would need to be accrued to explain the
modern day virulence phenotype of Yersinia. I would think that simultaneous
mutation of all the "wild type" genes to form their "mutant" virulent
specifying alleles within a single host an unlikely event. Too many
mutational events are required. (What is the mutation rate for nonselectible
markers in pathogens during infection anyway? is it higher than in vitro?)
I would hesitate calling the acquirement of virulence traits in pathogenic
organisms shortsighted for the following reasons:
1. In all of the examples used in the paper a significant proportion
of the ancestral strain (the strain from which the "new" virulent
mutant had arisen) could be passed on to another host. The
original genetic blueprint is still intact. In secondary hosts
this "ancestor" strain could mutate such that the "new" virulence
phenotype, as seen in the primary host, emerges. Although the
actual genetic changes may differ the phenotype is redundent.
I would think that the genetic changes would have to affect the same
locus involved in the "new" virulence trait due to the "selective
pressure" from the host. In this case the mutation is also redundent.
2. Suppose that eventually the host evolves in such a fashion that
transmission of the organism to new host, after mutating to the "new"
virulence phenotype, may occur?
To bypass all of my wind above I don't think that evolution towards
virulence by a parasite in a host may be all that short sighted. The "blind
alley" aproach by the parasite (i.e. mutating to fill a niche from which there
will only be limited replication of the genome) may be another strategy that
the parasite has evolved in order "to explore" new replication possibilities.
Just my two cents,
NOTE: The above opinions are ________________________________
not meant to reflect the views As Homer would say:
of the U.S.U.H.S., Navy, or
the Military. They are the DOH! :-0
views of the author only. ________________________________
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