Yersinia pestis Biofilm in the Flea Vector and Its Role in the Transmission of Plague

Abstract

Transmission by fleabite is a relatively recent evolutionary adaptation of Yersinia pestis, the bacterial agent of bubonic plague. To produce a transmissible infection, Y. pestis grows as an attached biofilm in the foregut of the flea vector. Biofilm formation both in the flea foregut and in vitro is dependent on an extracellular matrix (ECM) synthesized by the Yersinia hms gene products. The hms genes are similar to the pga and ica genes of Escherichia coli and Staphylococcus epidermidis, respectively, that act to synthesize a poly-β-1,6-N-acetyl-dglucosamine ECM required for biofilm formation. As with extracellular polysaccharide production in many other bacteria, synthesis of the Hms-dependent ECM is controlled by intracellular levels of cyclic-di-GMP. Yersinia pseudotuberculosis, the food-and water-borne enteric pathogen from which Y. pestis evolved recently, possesses identical hms genes and can form biofilm in vitro but not in the flea. The genetic changes in Y. pestis that resulted in adapting biofilm-forming capability to the flea gut environment, a critical step in the evolution of vector-borne transmission, have yet to be identified. During a flea bite, Y. pestis is regurgitated into the dermis in a unique biofilm phenotype, and this has implications for the initial interaction with the mammalian innate immune response.

Roles of pgaABCD Genes in Synthesis, Modification, and Export of the Escherichia coli Biofilm Adhesin Poly-β-1,6- N -Acetyl- d -Glucosamine

“…Poly-␤-1,6-GlcNAc has profound effects on hostmicrobe interactions. It apparently promotes the transmission of the plague bacillus Yersinia pestis from the flea vector to the mammalian host (22,26) and affects colonization, virulence, and immune evasion in infections caused by gram-positive and gram-negative species (see references 4, 8, 9, 24, 41, and 48).…”

Synthetic β-(1→6)-Linked N-Acetylated and Nonacetylated Oligoglucosamines Used To Produce Conjugate Vaccines for Bacterial Pathogens

“…Among important bacterial pathogens, PNAG is known to be produced by S. aureus and Staphylococcus epidermidis (23,25,26), E. coli (13,42), Bordetella pertussis and Bordetella parapertussis (29,36), Aggregatibacter actinomycetemcomitans (15), Acinetobacter spp. (8), and Yersinia pestis (10,12). Based on genetic homology, loci likely encoding PNAG biosynthetic proteins are found in Burkholderia cenocepacia and Klebsiella pneumoniae.…”

Formation and regulation of Yersinia biofilms

“…The development of heavy bacteremia in rodents is crucial to reliably infect fleas, which transmit the disease by biting a new host animal (Lorange et al, 2005). Infected fleas often develop "blockage" in the proventriculi of fleas (Darby, 2008;Hinnebusch and Erickson, 2008). Y. pestis synthesizes biofilms to attach onto the surface of the proventricular spines, and the heavy bacterial proliferation in the biofilms promotes the blockage of the gut of fleas (see reference (Darby, 2008) for a schematic representation of a blocked flea).…”