A refined model of how Yersinia pestis produces a transmissible infection in its flea vector
Open Access
- 15 April 2020
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Pathogens
- Vol. 16 (4), e1008440
- https://doi.org/10.1371/journal.ppat.1008440
Abstract
In flea-borne plague, blockage of the flea's foregut by Yersinia pestis hastens transmission to the mammalian host. Based on microscopy observations, we first suggest that flea blockage results from primary infection of the foregut and not from midgut colonization. In this model, flea infection is characterized by the recurrent production of a mass that fills the lumen of the proventriculus and encompasses a large number of Y. pestis. This recurrence phase ends when the proventricular cast is hard enough to block blood ingestion. We further showed that ymt (known to be essential for flea infection) is crucial for cast production, whereas the hmsHFRS operon (known to be essential for the formation of the biofilm that blocks the gut) is needed for cast consolidation. By screening a library of mutants (each lacking a locus previously known to be upregulated in the flea gut) for biofilm formation, we found that rpiA is important for flea blockage but not for colonization of the midgut. This locus may initially be required to resist toxic compounds within the proventricular cast. However, once the bacterium has adapted to the flea, rpiA helps to form the biofilm that consolidates the proventricular cast. Lastly, we used genetic techniques to demonstrate that ribose-5-phosphate isomerase activity (due to the recent gain of a second copy of rpiA (y2892)) accentuated blockage but not midgut colonization. It is noteworthy that rpiA is an ancestral gene, hmsHFRS and rpiA2 were acquired by the recent ancestor of Y. pestis, and ymt was acquired by Y. pestis itself. Our present results (i) highlight the physiopathological and molecular mechanisms leading to flea blockage, (ii) show that the role of a gene like rpiA changes in space and in time during an infection, and (iii) emphasize that evolution is a gradual process punctuated by sudden jumps. Plague is a deadly flea-borne disease caused by the bacillus Yersinia pestis. This bacterium blocks the flea's foregut (proventriculus) to increase its likelihood of being regurgitated by fleas trying to take a blood meal. Understanding the mechanisms leading to flea blockage may help to find ways of controlling plague. Here, we propose a model in which blockage results from primary infection of the foregut and not from midgut colonization. In the proventriculus, Y. pestis induces, resists and then consolidates the formation of a bactericidal matrix that can be recurrently dislodged by a blood meal before it becomes firmly anchored to the proventriculus and thus definitively obstructs it. Induction, resistance, and then consolidation of the mass in the proventriculus were made possible by the sequential acquisition of genetic material by the ancestors of Y. pestis and by Y. pestis itself–emphasizing that evolution is a gradual process punctuated by sudden jumps.Keywords
Funding Information
- Agence Nationale de la Recherche (ANR-15-CE39-0017)
This publication has 54 references indexed in Scilit:
- Induction of the Yersinia pestis PhoP-PhoQ Regulatory System in the Flea and Its Role in Producing a Transmissible InfectionJournal of Bacteriology, 2013
- Hfq Regulates Biofilm Gut Blockage That Facilitates Flea-Borne Transmission of Yersinia pestisJournal of Bacteriology, 2012
- Localization of an accessory helicase at the replisome is critical in sustaining efficient genome duplicationNucleic Acids Research, 2010
- Biofilm formation is not required for early-phase transmission of Yersinia pestisMicrobiology, 2010
- The helicases DinG, Rep and UvrD cooperate to promote replication across transcription units in vivoThe EMBO Journal, 2009
- TheYersinia pestis caf1M1A1Fimbrial Capsule Operon Promotes Transmission by Flea Bite in a Mouse Model of Bubonic PlagueInfection and Immunity, 2009
- Experimental evidence for negative selection in the evolution of a Yersinia pestis pseudogeneProceedings of the National Academy of Sciences of the United States of America, 2008
- Resistance of Yersinia pestis to Complement-Dependent Killing Is Mediated by the Ail Outer Membrane ProteinInfection and Immunity, 2008
- Early-phase transmission of Yersinia pestis by unblocked fleas as a mechanism explaining rapidly spreading plague epizooticsProceedings of the National Academy of Sciences of the United States of America, 2006
- Transmission ofYersinia pestisfrom an Infectious Biofilm in the Flea VectorThe Journal of Infectious Diseases, 2004