Research reveals evolution of deadly new Salmonella strain
2 December 2009
The genetic changes that transformed a previously mild salmonella infection into a new antibiotic-resistant form of the disease have now been described by researchers from the Wellcome Trust Sanger Institute, the Malawi-Liverpool-Wellcome Trust Clinical Research Programme and the KEMRI-Wellcome Trust Programme in Kenya.
The new form of the strain ST313 appears to be better adapted to affect humans than the common form of Salmonella Typhimurium, is resistant to several commonly used antibiotics and may spread from person-to-person. It infects vulnerable children and adults in many regions of sub-Saharan Africa leading to death in up to one in four cases.
The normal ST313 form of S. Typhimurium causes diarrhoea and is rarely fatal. Scientists originally thought the strain acted passively, taking advantage of weakened immune systems, such as those suffering from HIV, malaria, malnutrition or anaemia. But the new study shows that it is actually more invasive and has developed into a more dangerous, drug-resistant form.
"This is a new form of pathogen," said Dr Robert Kingsley from the Sanger Institute. "It seems to have evolved to acquire a unique armoury that allows it to infect vulnerable children and adults efficiently in some African regions."
Multidrug-resistant ST313 has swept through humans in remarkable fashion: in an 18-month period beginning in 2002, it represented 95 per cent of S. Typhimurium isolates identified in Africa.
The researchers studied around 50 samples of ST313 DNA, extracted from blood samples of African patients with severe symptoms of infection and also suffering HIV, malaria, malnutrition or anaemia. They then compared the combined genetic sequence from these samples with those of strains causing milder disease symptoms.
"We saw genetic signatures that suggested ST313 may be adapting to humans," said Dr Kingsley. "For example, this deadly strain has lost around one in 50 of the genes found in the 'typical' S. Typhimurium - a classic sign that it may be becoming more closely adapted to one host, in this case, humans."
The findings suggest that ST313 may be spreading by a new method, not seen before in S. Typhimurium. The pathogen normally circulates among animals and is introduced to humans through food poisoning. However, ST313 may be passing predominantly from person to person and so can adapt more rapidly to its human hosts.
"Our findings show that ST313 has acquired a block of genes that make it resistant to the common antibiotics," said Dr Chisomo Msefula from the Malawi-Liverpool-Wellcome Trust Clinical Research Programme. "Even when treated using drugs against which the bacterium has not gained resistance, the mortality rate remains staggeringly high, at 25 per cent."
"If we can understand what's special about the types of Typhimurium that emerge and susceptible populations, we might be able to predict in future where new pathogens will emerge," said Professor Gordon Dougan from the Sanger Institute. "We may also be able to design vaccines against those pathogens."
Image: Color-enhanced scanning electron micrograph showing Salmonella typhimurium (red) invading cultured human cells. Credit: Rocky Mountain Laboratories, NIAID, NIH
Reference
Kingsley RA et al. Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. Genome Res. 2009 Nov 9. [Epub ahead of print]