Accidently Typhoid Toxin Discovered

It's frequently happens in case of science that things are discovered by accident. Alexander Fleming discovered the secrets of antibiotics with a bout of chance – together with an intelligent mind to recognize his good fortune. Currently, it seems that scientists at Yale University have luckily found out, too: they've discovered the real cause of typhoid fever. 

Typhoid fever is a disease that use to affect people dates back to before ancient Greece and still causes as many as 200,000 deaths globally each year, about the population of Birmingham, Ala. For many years, the cause of typhoid fever has remained a mystery. But a paper published last week in Nature exposed the true cause of the disease. 

Jorge Galan, the study's author said that it is  the oldest identifiable disease, it distraught Athens and is credited as the main reason why the Spartans beat the Athenians in war.

It's been recognized for some time that the bacterium which is the cause for the disease is Salmonella typhi, but in spite of mankind's long history with the microbe, we've really been unknown to why this bug is so pathogenic, even if it's a close relative of the other salmonella sickness, food poisoning. 

One of the reasons why human race has been ignorant to the mechanism of S. typhi is because it's a somewhat ignored disease without many researchers functioning on it, said leading typhoid fever expert Dr. Zulfiqar Bhutta, from Aga Khan University in Pakistan. 

Galan's research now discovers how S. typhi has managed to keep its stealth for so long. Its deadliness comes from a novel life strategy: it doesn't free its toxin until it's determinedly inside a mammalian host cell. Normally when microbiologists search for a possible toxin produced by a microbe, they grow the organism in a culture and then crush it up and search for a candidate compound inside the mixture. But S. typhi does not fabricate a toxin unless you've permitted it to enter a host cell, so you couldn't probably find it using conventional methods.

Galan, however, manage a  protocol to look at the microbe after it had infected a host cell. "We happened to be studying the interaction of [S. typhi] with human cells, we weren't in the business of trying to find the typhoid toxin, we just bumped into this," said Galan. 

Once contained by a mammalian host cell, the typhoid bacterium begins to produce the toxin, which is then packaged into courier vessels to be unleashed. 

"The toxin is dumped outside of the cell where the bacterium resides and it enters the blood system to hit its target," said Galan. 

Once Galan had recognized what he thought could be the toxin responsible for typhoid disease, he isolated and purified it. He then infected mice with it and found that its result in typhoid symptoms in the mice, except fever, which is an immune response to the occurrence of the bacterium rather than the toxin itself. 

"I think this is an absolutely fascinating paper, but it's only the first step in the right direction," said Bhutta. "This particular study looked at mutant strains [of S. typhi], the next step is to work out how much of this is true in real life. How much of this can be replicated by other researchers?" 

Bhutta said that it's still "too early to say whether this is a turning point or not," towards the possible eradication of the disease. 

Galan on the other hand said it will be "scientifically trivial" to produce an efficient vaccine from an inactivated version of the toxin he discovered – though he concede that the feasibility of the matter, such as finding enough funding, present a more formidable challenge. 

At present, typhoid treatment relies on a course of antibiotics that targets the bacteria rather than the toxin; occasionally even that fails. 

"There are many instances in which people receive antibiotics but they still can't pull out of the disease. Clearly the bacteria is no longer there. They eventually die. Our hypothesis is that the toxins are still circulating around," said Galan.