The idea of a journal club for bio.microbiology, raised in an earlier
thread by Martin Latterich, seems pretty good to me. I'm not quite
sure what format Martin had in mind, but here's my attempt at a
kick-off. I've tried to combine a review of a paper with a few
provocative by-lines, to try to stimulate discussion in this thread.
"Short-sighted evolution and the virulence of pathogenic micro-
organisms", by Bruce Levin and James Bull, 1994, Trends in
Microbiology, 2 (3);76-81.
This paper puts forward a new answer to the question "why
virulence?" (or "what is the selective value of virulence?" for those
of you who don't like teleological questions). Before looking at this
new answer, let's look at some of the older ideas on the subject.
HYPOTHESIS ONE:Virulence is a sign of immaturity
One traditional answer to this question, not discussed by Levin &
Bull, is that virulence is a sign of an immature host-pathogen
relationship--the smartest parasites evolve so as to minimise damage
to their hosts. The only two bits of evidence that I've come across to
support this argument are the reports of the rabbit/myxomatosis
interaction in Australia and of the avian origin of the most virulent of
the human malarial parasites, P. falciparum (anyone got any other
examples?). I don't think many people, apart from those who write
textbooks :-) , take this argument seriously any more (anyone wish
to disagree?).
Levin & Bull discuss two established hypotheses to account for the
evolution of virulence in addition to their novel explanation of
virulence:
HYPOTHESIS TWO:Virulence is co-incidental
"...virulence is a co-incidental by-product of some other feature
of the phenotype of a microparasite. In this 'co-incidental virulence'
hypothesis, the genes responsible for the pathology evolved for
some other function (possibly in a different host)."
A possible example that springs to my mind here is legionellosis,
where one might hypothesise that the virulence factors involved in
human disease evolved to enable the bacteria to infect amoebas. Any
legionellologists wish to comment?
HYPOTHESIS THREE:Virulence is adaptive
"..virulence is itself adaptive:the host morbidity and mortality
resulting from infection is to the advantage of the parasite for its
transmission between hosts".
Ewald discussed this sort of thing in Scientific American in April
last year (and in a book, which I've not yet seen--anyone read it? is
it any good?). This hypothesis appears to fit the bill for many
infectious diseases--it seems reasonable to me to suppose that
cholera, the disease, helps transmit V. cholerae, the bacterium (but
some other diarrhoeal diseases may fit the co-incidental evolution
model better, e.g. salmonella or yersinia gastro-enteritis, where
human-to-human spread is usually unable to sustain the pathogen in
human populations).
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
them, that
"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.
I found Levin & Bull's paper stimulating and provocative. I would
urge readers to take a look at it, and then think about the pathogens
and diseases that they are working on. Which of the hypotheses
outlined above fit(s) your organism? (NB the above hypothesis are
not mutually exclusive.)
Here are a few more provocative questions to stimulate the
discussion:
Is the acquisition of mucoidy by Pseudomonas aeruginosa in CF
patients an example of short-sighted virulence--are the mucoid forms
actually transmitted between patients?
How far is the emergence of secondary drug resistance in
tuberculosis an example of short-sighted virulence, given that drug
resistance is said to be associated with decreased virulence in
experimental animals.
Why is Staphylococcus aureus so virulent? What selective advantage
does all that cellulitis, pus and tissue destruction bring? Is an
example of co-incidental evolution--does tissue destruction aid
transmission in bovine mastitis--or is an example of short-sighted
virulence again?
Are the adaptations towards increased fitness in stationary phase,
described by Zambrano, Kolter et al short-sighted, in the sense that
bacteria bearing them are less fit in log phase. Are the organisms that
grow back out of stationary phase into log phase derived from a
minority population that is relatively unfit at stationary-phase
survival?
And, finally... if Levin & Bull are listening in... Sorry if I've
misrepresented or distorted or simplified your ideas--at the very least
I'll have stimulated people to read your paper!
"Most people are other people. Their thoughts are someone else's
opinions, their lives a mimicry, their passions a quotation."
Oscar Wilde
Mark Pallen: m_pallen at v1.barts.lon.ac.uk
or mpallen at seqnet.dl.ac.uk
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