Antibiotic Resistant Salmonella Typhimurium Emerges in Africa

A new multi drug resistant strain of Salmonella typhimurium is causing life-threatening disease in Africa.

Genetic changes in the organism transformed this infection into a new antibiotic-resistant form of the disease. The new strain, called ST313, appears to be better adapted to affect humans, is resistant to several commonly used antibiotics, and may spread from person to person.

A team of scientists studied approximately 50 samples of the bacterial DNA, extracted from blood samples of African patients with severe symptoms of infection and suffering from HIV, malaria, malnutrition, or anemia. They used these samples to produce a high-quality reference genome sequence. Based on this sequence, the team was able to look in fine detail at the genetic differences between ST313 and strains associated with milder disease symptoms across the globe.

The severe effects of ST313--invasive disease and high mortality rates--are seen predominantly in individuals with the immune compromising conditions, HIV, malaria, malnutrition, or anemia. It had been assumed that this wasn't a new deadly form of the organism but, rather, that the existing diarrhea causing strain of the pathogen was taking advantage of the weakened immune system of patients with underlying health problems to cause a more severe disease.

"When we started looking in detail at our newly completed reference genome sequence, we saw the genetic signatures that suggested it might be adapting to humans," explained Dr Robert Kingsley from the Welcome Trust Sanger Institute (Cambridge, UK). "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 scientists also found patterns of genome degeneration. Six out of 10 of the regions that showed degradation in the invasive ST313 are also degraded in S. typhimurium, suggesting that the genomes have converged in their ability to thrive in the human host. This theory is supported by the finding that eroded areas of the genome tend to play important roles in the intimate interaction with cells of the human host.

The team's findings suggest that ST313 may be spreading by a new method, not seen before in S. typhimurium. The pathogen normally circulates among animals and it is introduced to humans through food poisoning. It spends much of its time in the animal hosts. However, ST313 may be passing predominantly from person to person and so can adapt more rapidly to its human hosts: it does not spend time acquiring mutations to help it thrive in the animal host; in fact, it may be losing them.

However, ST313 acquired a block of genes that make it resistant to the common antibiotics. The genes jumped into ST313 on a mobile genetic element called a transposon, bringing with it additional genes that make the strain more deadly.

The study was published in the December 8, 2009 edition of the journal Genome Research.

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Welcome Trust Sanger Institute