Gene switch that turns bacteria into mighty Hulk
It's the kind of biological horror story you couldn't make up.
Tiny nematode worms burrow into moth larvae guts and release a biological weapon: bacteria that switch from feeble, dormant passengers in the worm's intestine to the bacterial version of the Hulk – except they're red.
Todd Ciche and colleagues at Michigan State University in East Lansing have found that just one gene, randomly switching back and forth between two states, transforms tiny, quiescent bacteria into big, red, glowing killers – a process that may reveal how important human infections like antibiotic-resistant staphylococcus, or MRSA, persist.
Some individuals belonging to one species of nematode worm, Heterorhabditis bacteriophora start life by killing their own mother.
They hatch inside her uterus instead of waiting for her to lay her eggs.
While breaking out – and killing mum – those babies acquire a load of Photorhabdus luminescens bacteria from her body cavity, a gift denied siblings hatched the conventional way.
The tiny, translucent bacteria colonise the baby worms' guts – then go to sleep.
The baby worms then crawl through the soil and into the guts of moth larvae – through its mouth, anus or breathing pores, or just by slashing their way in with a fang.
Once in the larva's gut, the worms vomit up their bacterial passengers.
But these are no tiny dormant gut-clingers: they are seven times larger than 'normal' P. luminescens, glowing red and exuding larva-killing toxins.
Both the bacteria and the worm then feast on the corpse.
The bacteria multiply, process nutrients for the worm and signal it to reproduce – which it does, spawning half a million babies in a two-week infestation.
Wimps to warriors
"The nematode depends on the bacteria to reproduce in addition to killing the insects," says Ciche.
Both then go on to kill again. In fact, you can buy the worms on the internet to kill larval infestations in your lawn.
Biologists studying this ghoulish life cycle knew about the Hulk bacteria but were puzzled by their wimpy alter egos.
Ciche previously found that the Hulk form allows the worm to kill and eat larvae, while the wimps adhere to the mother-worm's anus and burrow into its body cavity to infect the next generation.
The team has now discovered that both kinds are in fact in the worm all the time, and one simple, small stretch of DNA triggers the switch from wimp to Hulk and back.
Locking this madswitch – so-called because it promotes maternal adhesion – stopped the bacteria from switching and infesting new baby worms or parasitising moth larvae.
Surprisingly, the switch flips on and off spontaneously.
"Dogma is that the bacteria would sense a cue or signal and regulate gene expression in response," says Ciche – for instance, turning into Hulks only in the larva's gut. Instead, they use a "bet-hedging strategy" in which they keep both the attacking and colonising forms just in case they get a chance to shine.
Ciche suspects similar Jekyll-and-Hyde transformations occur in human infections.
A stretch of DNA similar to the madswitch regulates gene expression in Escherichia coli that causes fatal disease in humans, such as the one that struck Germany last year.
They may switch bacteria into attack mode to counter antibiotics or the human immune system.
But the wimp bacteria may also be useful.
Similar, slow-growing cells have been found in nasty human bacterial infections such as salmonella or MRSA.
As these are in suspended animation, they are less vulnerable to antibiotics, which attack during bacterial growth – the wimp bacteria in the worms were a hundred times less sensitive to antibiotics than the killers.
Ciche suspects some human infections use such mild-mannered forms to dodge attack, perhaps using some of the same genes