Gallego-Hernandez AL, DePas WH, Park JH, Teschler JK, Hartmann R, Jeckel H, Drescher K, Beyhan S, Newman DK, Yildiz FH
Upregulation of virulence genes promotes Vibrio cholerae biofilm hyperinfectivity.
Proceedings of the National Academy of Sciences of the United States of America. 2020-04-30;
remains a major global health threat, disproportionately impacting parts of the world without adequate infrastructure and sanitation resources. In aquatic environments, exists both as planktonic cells and as biofilms, which are held together by an extracellular matrix. biofilms have been shown to be hyperinfective, but the mechanism of hyperinfectivity is unclear. Here we show that biofilm-grown cells, irrespective of the surfaces on which they are formed, are able to markedly outcompete planktonic-grown cells in the infant mouse. Using an imaging technique designed to render intestinal tissue optically transparent and preserve the spatial integrity of infected intestines, we reveal and compare three-dimensional colonization patterns of planktonic-grown and biofilm-grown cells. Quantitative image analyses show that colonizes mainly the medial portion of the small intestine and that both the abundance and localization patterns of biofilm-grown cells differ from that of planktonic-grown cells. In vitro biofilm-grown cells activate expression of the virulence cascade, including the toxin coregulated pilus (TCP), and are able to acquire the cholera toxin-carrying CTXФ phage. Overall, virulence factor gene expression is also higher in vivo when infected with biofilm-grown cells, and modulation of their regulation is sufficient to cause the biofilm hyperinfectivity phenotype. Together, these results indicate that the altered biogeography of biofilm-grown cells and their enhanced production of virulence factors in the intestine underpin the biofilm hyperinfectivity phenotype.