Salmonella gets its host to arm its secret weapon
Bacteria wield all sorts of molecular weapons that allow them to infiltrate their hosts. But one microbe – Salmonella enterica – has a particularly devious trick. It uses weapons that arm themselves by manipulating the host’s own proteins. When this bacterium infects cells, it turns them into accomplices to their own downfall.
S.enterica causes a variety of different illnesses including food poisoning and typhoid fever. There are over 2,500 different varieties and Chittur Srikanth from Harvard Medical School has been studying one called Typhimurium, which infects mice. In the first moments of infection, Typhimurium injects a small arsenal of proteins into its victim, which subvert its structure, defences and communications.
One of these injected weapons is known appropriately enough as SipA, or Salmonella invasion protein A. It has two business ends, both of which pose a threat to a host cell. One of them causes a host protein called actin to clump together into long filaments. These act as guide ropes that help to draw Salmonella into the cell. The other end of SipA causes white blood cells to enter the lining of the intestines, leading to inflammation and diarrhoea – a symptom that allows Salmonella to spread from one individual to another.
The problem is that SipA – in its initial form – doesn’t do either job very well. The protein needs to be split in two so that each end can go about its business separately. To do that, it recruits one of its host’s own proteins – a molecular executioner called caspase-3.
Caspases cut up other proteins. Their hacking and slashing typically provides a way for damaged or unwanted cells to commit suicide, but they can also encourage cells to divide and trigger inflammation. Srikanth found that caspase-3 cuts SipA right down the middle, producing two proteins when once there was one.
This is an essential event. When Srikanth engineered a version of SipA without the amino acids that normally attract caspase-3, the protein couldn’t be cleaved in two. As a result, Salmonella’s invasion was cut short. Infected mice showed no signs of inflamed bowels or symptoms of food poisoning.
It might seem that Salmonella is unduly reliant on its host; after all, its weapon stays capped unless it gets a hand from caspase-3. But the bacterium takes a more active hand than that. Srikanth found that SipA actually activates caspase-3, producing more of the very protein that it needs to activate itself.
This trick isn’t limited to SipA. Other proteins that are injected by Salmonella, and those from other gut bacteria like Escherichia coli and Shigella flexneri, also carry targets for caspase-3. And the majority of these proteins, like SipA, have two functions, with different ends performing different jobs.
Srikanth thinks that the release of caspase-3 in the lining of the intestine may originally have evolved as a defence against invading bacteria, helping to kill or disarm the intruders. However, it seems that a whole host of bacteria have managed to subvert these defences, using the executioner protein to activate and double their own arsenal.
Reference: Science http://dx.doi.org/10.1126/science.1194598
More on infectious bacteria:
- Why gonorrhoea is like a general sabotaging his own siege
- Disease by coincidence – why we’re caught in the crossfire of a hidden war
- When bacteria fight bacteria, we lose
- MRSA in pigs and pig farmers
- Super-bacteria eat antibiotics for breakfast
Go Further
Animals
- Soy, skim … spider. Are any of these technically milk?Soy, skim … spider. Are any of these technically milk?
- This pristine piece of the Amazon shows nature’s resilienceThis pristine piece of the Amazon shows nature’s resilience
- Octopuses have a lot of secrets. Can you guess 8 of them?
- Animals
- Feature
Octopuses have a lot of secrets. Can you guess 8 of them? - This biologist and her rescue dog help protect bears in the AndesThis biologist and her rescue dog help protect bears in the Andes
Environment
- This pristine piece of the Amazon shows nature’s resilienceThis pristine piece of the Amazon shows nature’s resilience
- Listen to 30 years of climate change transformed into haunting musicListen to 30 years of climate change transformed into haunting music
- This ancient society tried to stop El Niño—with child sacrificeThis ancient society tried to stop El Niño—with child sacrifice
- U.S. plans to clean its drinking water. What does that mean?U.S. plans to clean its drinking water. What does that mean?
History & Culture
- Gambling is everywhere now. When is that a problem?Gambling is everywhere now. When is that a problem?
- Beauty is pain—at least it was in 17th-century SpainBeauty is pain—at least it was in 17th-century Spain
- The real spies who inspired ‘The Ministry of Ungentlemanly Warfare’The real spies who inspired ‘The Ministry of Ungentlemanly Warfare’
- Heard of Zoroastrianism? The religion still has fervent followersHeard of Zoroastrianism? The religion still has fervent followers
- Strange clues in a Maya temple reveal a fiery political dramaStrange clues in a Maya temple reveal a fiery political drama
Science
- Soy, skim … spider. Are any of these technically milk?Soy, skim … spider. Are any of these technically milk?
- Can aspirin help protect against colorectal cancers?Can aspirin help protect against colorectal cancers?
- The unexpected health benefits of Ozempic and MounjaroThe unexpected health benefits of Ozempic and Mounjaro
- Do you have an inner monologue? Here’s what it reveals about you.Do you have an inner monologue? Here’s what it reveals about you.
- Jupiter’s volcanic moon Io has been erupting for billions of yearsJupiter’s volcanic moon Io has been erupting for billions of years
Travel
- Follow in the footsteps of Robin Hood in Sherwood ForestFollow in the footsteps of Robin Hood in Sherwood Forest
- This chef is taking Indian cuisine in a bold new directionThis chef is taking Indian cuisine in a bold new direction
- On the path of Latin America's greatest wildlife migrationOn the path of Latin America's greatest wildlife migration
- Everything you need to know about Everglades National ParkEverything you need to know about Everglades National Park