快猫短视频

SOME would call it the ultimate feminist weapon鈥攁 bacterial parasite
that wages a tireless crusade against males and maleness. In some species, it
turns infected males into females. In others, it prevents males from being born.
In still others, it snuffs out any males it infects. This microscopic terrorist
can even alter its method of attack to match the ecology and genetics of its
host.

You may be relieved to hear that the bacterium in question,
Wolbachia, affects insects and worms rather than humans. Nevertheless, it
is probably doing its sexual cleansing right under your nose. Even the ladybirds
munching aphids in your garden are likely to be taking orders from these
bacteria. Wolbachia turns out to be one of the world鈥檚 commonest
parasitic microbes, and it may infect most major groups of invertebrates.

Wherever researchers have looked for it, it鈥檚 there鈥攂e it a Panamanian
jungle, a street in Moscow or an American backyard. At a conservative estimate,
it lurks in at least a fifth of the world鈥檚 insect species, 5 million in all.
鈥淎nd so far, we鈥檝e just scratched the surface,鈥� says Jack Werren of the
University of Rochester, New York, who has looked for Wolbachia鈥檚
molecular fingerprint in samples of insect life from all over the world. 鈥淲e
still don鈥檛 know the limits of its incredibly wide distribution.鈥�

How Wolbachia has become such a widespread and devious influence is
now the focus of intensive research in more than a dozen labs around the world.
The race is on to discover the secrets of its remarkable powers, and the winners
could earn a huge payoff. These strange bacteria could not only provide powerful
new ways of genetically disarming insect pests, they may even hold clues to
human infertility or the perfect male contraceptive pill. 鈥淭he field is going to
explode in the next couple of years,鈥� predicts Scott O鈥橬eill, a geneticist at
Yale University.

Wolbachia鈥檚 disdain for males makes perfect sense from the microbe鈥檚
point of view. It lives within its host鈥檚 cells and relies on the cytoplasm of
the egg to ferry it into the next generation. Males are useless to
Wolbachia, because their sperm cells contain virtually no cytoplasm, so any
bacteria harboured by a male die with him and cannot spread. As a result, these
bacteria do all they can to enhance the survival and mating prospects of the
females that transmit them and to decrease the reproductive fitness of the males
that don鈥檛.

Sometimes, as with woodlice, Wolbachia takes the direct approach:
turning the males into females. The bacteria somehow interfere with the action
of a male hormone normally secreted by the woodlouse鈥檚 androgenic gland. If it
does this in a developing embryo, it suppresses the gland and the gonads develop
into ovaries. But even adult males develop female genitalia once infected.

Thierry Rigaud and his colleagues at the University of Poitiers in France
have now found the gene for the androgenic hormone and are trying to understand
how the bacterium interferes with the gene鈥檚 action. Wolbachia鈥檚
feminisation strategy seems confined to woodlice and their isopod relatives,
perhaps because, with their sex determined by a single hormone, these animals
are relatively easy targets.

If feminisation isn鈥檛 possible, the bacteria try to eliminate male offspring,
either by killing them (see 鈥淔amily dinners鈥�) or by avoiding their birth
altogether. Researchers have long known that strains of some insect species can
reproduce asexually, producing only daughters through a kind of virgin birth.
But in 1990, Richard Stouthamer discovered that he could cure a species of
Californian wasp of the habit by giving it a dose of antibiotics. Stouthamer,
who is now at the Wageningen Agricultural University in the Netherlands, went on
to confirm that Wolbachia lurked in the eggs of asexual females. The
bacteria must somehow manipulate the behaviour of the eggs鈥� chromosomes, causing
them to double at just the right time and thus allow females to reproduce
asexually, says Stouthamer.

When it is unable to find a more elegant way of increasing the fitness of its
female hosts, Wolbachia turns to cruder tactics: it prevents infected
males from fertilising uninfected females. By ensuring that such matings fail,
the bacterium effectively uses the males as sexual decoys to keep uninfected
females childless, thus opening the field to the offspring of
Wolbachia-bearing females. How it accomplishes this so-called 鈥渃ytoplasmic
incompatibility鈥� is still a mystery. One theory is that Wolbachia
produces a blocking protein that binds to the sperm鈥檚 chromosomes and can be
removed only by a 鈥渞escue factor鈥� produced within infected eggs.

A side effect of this stratagem may be to promote the evolution of new
species by creating reproductive barriers between populations bearing different
strains of Wolbachia. Such reproductive isolation would allow the
groups to follow different evolutionary paths and eventually diverge into
separate species. This may have already happened in a group of small parasitic
wasps known as jewel wasps, says Werren.

In the lab, he noticed that although three different species of jewel wasp
will mate with one another, they never produced hybrid offspring. The barriers
broke down, however, when the laboratory wasps were given a dose of antibiotics.
鈥淲hen we cured the wasps of their Wolbachia infections and repeated the
crosses, true hybrid progeny developed,鈥� he says. 鈥淚n other words, reproductive
isolation proved to be `curable鈥�.鈥� No one yet knows how often Wolbachia
infections may have fostered the emergence of new species. But as Werren points
out, 鈥渆ven if intracellular parasites like Wolbachia have played a role
in the evolution of just 5 per cent of insects, it puts a significant new twist
on the origin of species.鈥�

Wolbachia is also remarkably adaptable in its choice of strategy. Closely
related strains often have totally different effects on their hosts.
Male-killing, for instance, is not linked with any particular Wolbachia
lineage. Male-killing variants are closely related to those that cause
cytoplasmic incompatability, asexual reproduction or even feminisation, says
Rigaud. So it looks as though Wolbachia is able to quickly adopt a
different mode of attack to exploit the particular vulnerability of whatever
host it finds itself in. 鈥淚t鈥檚 the characteristics of the host鈥攊ts ecology
and genetics鈥攖hat determine what Wolbachia decides to do,鈥� says
Michael Majerus, an evolutionary geneticist at the University of Cambridge.

What鈥檚 more, the bacterium is not even confined to arthropods such as
insects, spiders and crustaceans. Four years ago, Wolbachia surprised
everyone when Claudio Bandi and his colleagues at the University of Milan found
them in some nematode roundworms. The worms they were found in are parasites of
vertebrates, and some can cause nasty diseases such as elephantiasis and river
blindness. So even humans can carry Wolbachia, albeit encased within
parasitic worms.

The wayward microbe may even be able to escape from its nematode host and
infect human tissues directly, suspects immunologist Mark Taylor of the
Liverpool School of Tropical Medicine. He has found Wolbachia DNA in
blood plasma from people with nematode infections.

No one knows how Wolbachia first got into nematodes, but whatever
happened, it was a long time ago: the worms and their parasites have evolved a
relationship so intimate that the nematodes now can鈥檛 live without them. If the
nematodes are 鈥渃ured鈥� of their Wolbachia by a dose of the antibiotic
tetracycline, the worms die. No one knows what the bacteria do for their host
that makes them indispensable. However, the discovery strengthens suspicions
that antibiotics could be powerful weapons against nematode infections in
humans, which have been notoriously difficult to treat. Clinical trials are now
under way in Tanzania, coordinated by Taylor and his colleagues.

Researchers are also beginning to peep into the molecular bag of tricks that
Wolbachia uses to manipulate its hosts. A new consortium aims to
sequence the genomes of three Wolbachia strains over two years, says
O鈥橬eill, who is coordinating the project. The prime targets are the strains that
infect nematodes, mosquitoes and fruit flies. 鈥淭he sequencing project should
give a huge boost to the whole field,鈥� says Henk Braig, a Wolbachia
researcher at the University of Wales at Bangor.

O鈥橬eill鈥檚 team at Yale University is already trying to manipulate
Wolbachia鈥檚 genome by knocking out some of its genes or introducing foreign
ones. 鈥淥nce we have these tools and the sequence data, we hope we can quickly
pull apart the molecular mechanisms at work in Wolbachia,鈥� he says. The
potential applications are legion.

One idea is to use Wolbachia鈥檚 selfishness to help distribute useful
genes through insect populations鈥攆or example, genes that block the ability
of mosquitoes to carry the malaria parasite that infects humans (New
快猫短视频, 5 August 1995, p 36). If researchers were to add
Wolbachia to their genetically modified mosquitoes, the antimalarial genes
could hitch a ride with the bacteria as they spread through the mosquito
population. Once researchers have identified the genes that cause cytoplasmic
incompatibility, they may eventually be able to use just these genes, rather
than the whole Wolbachia.

Another idea is to exploit a virulent strain of Wolbachia recently
discovered in fruit flies in Seymour Benzer鈥檚 lab at the California Institute of
Technology in Pasadena, California. Called 鈥減opcorn鈥�, this Wolbachia
strain proliferates out of control in the body cells and reproductive cells of
mature insects, 鈥減opping鈥� the cells from within and eventually killing the host.
Because only old mosquitoes and old individuals of many other pest species can
transmit infections to humans, popcorn could be used to weed out older insects
and keep the population forever young and harmless.

No one yet knows whether popcorn exists in the wild. At first glance, it
makes no evolutionary sense for a parasite to kill off its host. Yet popcorn may
persist even so, because it kills only after its host has reproduced. But
popcorn has a deeper significance, because it shows Wolbachia can alter
not just reproductive tissue but the other cells of the body as well. 鈥�
Wolbachia may be having lots of effects in body tissue,鈥� says O鈥橬eill.
鈥淪ince Wolbachia was discovered, scientists have been thinking about it
in the context of reproduction, but now it鈥檚 possible that Wolbachia is
having even more far-reaching effects. There is perhaps a whole new field
waiting to be opened up.鈥�

Research into Wolbachia is mushrooming, agrees Braig, who is currently
tracking down the bacterium in spiders. 鈥淓very month, it seems, a new group
starts up.鈥� And no wonder. 鈥淲e can learn such a lot from Wolbachia,鈥� he
says. The molecular machinery underlying cytoplasmic incompatibility, for
instance, could shed light on aspects of human infertility, he speculates, or
suggest an entirely new means of creating a contraceptive pill for men.

The secret may lie in Wolbachia鈥檚 ability to block the normal
interaction between maternal and paternal chromosomes during fertilisation.
Researchers are now eagerly searching for the molecular key鈥攖he
鈥渕odification factor鈥� that somehow marks infected males鈥� genomes in sperm and
the 鈥渞escue鈥� factor in the eggs of infected females.

Everyone agrees that Wolbachia probably has other
as-yet-undiscovered tricks up its genome for twisting its host鈥檚 reproductive
behaviour to its advantage. And everything suggests that there are many more
microbes every bit as weird as Wolbachia out there, just waiting to be
noticed. Already, Majerus, Gregory Hurst at University College London and their
colleagues all over the world have detected four male-killing bacteria unrelated
to Wolbachia in ladybirds alone. 鈥淲e found three different male killers
in the same species of ladybird after only a single day of collecting,鈥� says
Majerus.

An incredible diversity of microbial tricksters remains to be discovered,
agrees Rigaud. What we鈥檝e stumbled across so far, he reckons, may be just one
tree in the forest.

The most bloodthirsty trick in Wolbachia鈥檚 repertoire鈥攌illing
all the males it infects in some hosts鈥攑ays a big dividend to females and
the bacteria they carry. Ladybird beetles, for example, are ripe for
exploitation by male-killers, says Michael Majerus of Cambridge University.

Females lay their eggs in batches, which provides a convenient if
cannibalistic meal for the first larvae to hatch, found Majerus and Greg Hurst,
now at University College London. Snacking on a sibling is advantageous, because
young ladybirds are much smaller than their aphid prey and have trouble catching
them. As a result, many starve. But in ladybirds infected with Wolbachia
or any of several other male-killing bacteria, all the would-be
males are killed early in development, long before they hatch out of the eggs.
So the infected ladybird鈥檚 daughters can scavenge on their dead brothers, and
are much more likely to survive to reproduce themselves, which is good news for
the bacteria. The inevitable consequence is a severely biased sex ratio: in some
species of ladybirds, it鈥檚 common to find two females for every male, and the
sex ratio can become even more skewed in the females鈥� favour as Wolbachia
or another male-killing bacterium sweeps through a population.

So why haven鈥檛 ladybirds died out for lack of males? It turns out that
uninfected beetles are being produced all the time, Hurst and Majerus
discovered. Occasionally, a male-killing bacterium misses its ride from
generation to generation: up to a tenth of an infected female鈥檚 daughters may be
free of the bacterium. Even among Wolbachia, where transmission from
mother to daughter seems to have a success rate of almost 100 per cent, the few
uninfected daughters, together with uninfected migrants coming in, produce
much-needed males. And because the resident bacteria inevitably drain nutrients
from their host, the uninfected ladybirds can also produce more offspring.

Although both inefficient transmission and lowered breeding success sound
like bad news for Wolbachia in the short term, they are better than the
alternative. A bacterium that wiped out all males would soon go extinct along
with its spinster hosts.

That has nearly happened in two species of Wolbachia-infected
African butterfly investigated by Majerus鈥檚 graduate student Francis Jiggins.
Again, the butterflies鈥� caterpillars cannibalise eggs, making male-killing
beneficial to Wolbachia-infected females in these species. 鈥淭he
butterflies are virtually all female,鈥� says Majerus, 鈥渁nd probably most of the
females die virgins, as a result of the severe shortage of males.鈥� This peculiar
situation has encouraged the evolution of unusual mating behaviour. 鈥淎s males
become the limiting sex, there are signs of sex-role reversal,鈥� says Majerus,
with females courting males rather than vice versa.