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A team of scientists from the Institut Pasteur, the CNRS and Paris Diderot University has identified a new regulation mechanism that enables a pathogenic bacterium of the Streptococcus genus to rapidly adapt to its host. This study was published on January 16, 2014 in PLoS Pathogens. The mechanism in question enables the bacterium to minimize its exposure to the immune system while maintaining effective tissue colonization. This work was carried out on Streptococcus gallolyticus, an intestinal tract bacterium responsible for endocarditis and septicemia in the elderly.
Paris, January 24, 2014
Streptococcus gallolyticus (S. gallolyticus) is a bacterium of the intestinal flora, and is present in approximately 10% of the human population. It may become pathogenic in those with a compromised or fragile immune system and is an emerging cause of septicemia and endocarditis in the elderly. In addition, epidemiological studies indicate that there is a strong correlation – up to 65% - between S. gallolyticus endocarditis and colon cancer.
Shaynoor Dramsi and her team from the Institut-Pasteur/CNRS Gram-positive Pathogens Unit (led by Patrick Trieu-Cuot) have discovered and characterized a novel regulatory mechanism which enables S. gallolyticus to minimize its exposure to the immune system and therefore facilitate its dissemination in the bloodstream, ensuring optimal tissue colonization.
The mechanism identified involves the Pil1 pilus in S. gallolyticus. Pili are long, filamentous structures on the bacterial surface. The adhesive properties they confer to the bacterial cells are key to effective colonization of the host. Pili are also highly immunogenic, which means that they are easily detected by the immune system.
In this study, the scientists discovered why, in a population of S. gallolyticus, the Pil1 pilus is present different amounts between individual bacteria. They showed that Pil1 expression is controlled by genetic micro-rearrangements within a gene located upstream of the Pil1 gene.
These random rearrangements occur at a high frequency and result in highly variable levels of Pil1 between individual bacterial cells. The bacteria therefore have differing levels of adhesiveness and immunogenicity.
The system described by the scientists enables S. gallolyticus to reduce its susceptibility to immune response pressure, and represents a new bacterial persistence strategy within the host.
These results confirm the potential value of pili as a therapeutic target in the fight against infections caused by pathogenic bacteria of the Streptococcus genus.
Illustration - Copyright Institut Pasteur
Caption - Streptococcus gallolyticus observed under an electron microscope. Pil1 pili are shown as white beads.
Single cell stochastic regulation of pilus phase variation by an attenuation-like mechanism, PLoS Pathogens, January 16, 2014.
Camille Danne (1,2,3), Sarah Dubrac (1,2), Patrick Trieu-Cuot (1,2) and Shaynoor Dramsi (1,2)
1 Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram-Positif, F-75015 Paris, France
2 Centre National de la Recherche Scientifique, CNRS ERL3526, F-75015 Paris, France
3 Université Paris Diderot-Sorbonne Paris Cité, France
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