title: Yersinia pestis halotolerance illuminates plague reservoirs.
abstract: The plague agent Yersinia pestis persists for years in the soil. Two millennia after swiping over Europe and North Africa, plague established permanent foci in North Africa but not in neighboring Europe. Mapping human plague foci reported in North Africa for 70 years indicated a significant location at <3 kilometers from the Mediterranean seashore or the edge of salted lakes named chotts. In Algeria, culturing 352 environmental specimens naturally containing 0.5 to 70 g/L NaCl yielded one Y. pestis Orientalis biotype isolate in a 40 g/L NaCl chott soil specimen. Core genome SNP analysis placed this isolate within the Y. pestis branch 1, Orientalis biovar. Culturing Y. pestis in broth steadily enriched in NaCl indicated survival up to 150 g/L NaCl as L-form variants exhibiting a distinctive matrix assisted laser desorption-ionization time-of-flight mass spectrometry peptide profile. Further transcriptomic analyses found the upregulation of several outer-membrane proteins including TolC efflux pump and OmpF porin implied in osmotic pressure regulation. Salt tolerance of Y. pestis L-form may play a role in the maintenance of natural plague foci in North Africa and beyond, as these geographical correlations could be extended to 31 plague foci in the northern hemisphere (from 15°N to 50°N).
authors.affiliation: Aix Marseille Université, URMITE, UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine, 27 Bd Jean MOULIN, 13385 Marseille Cedex 5, France.|Laboratoire Biodiversité et Environnement: Interactions Génomes, Faculté des Sciences Biologiques Université des Sciences et de la Technologie Houari Boumediene, El Alia, Bab Ezzouar 16111, Algérie.
authors.forename: Maliya Alia
authors.initials: MA
authors.lastname: Malek
authors.affiliation: Aix Marseille Université, URMITE, UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine, 27 Bd Jean MOULIN, 13385 Marseille Cedex 5, France.|Laboratoire Biodiversité et Environnement: Interactions Génomes, Faculté des Sciences Biologiques Université des Sciences et de la Technologie Houari Boumediene, El Alia, Bab Ezzouar 16111, Algérie.
authors.forename: Idir
authors.initials: I
authors.lastname: Bitam
authors.affiliation: Aix Marseille Université, URMITE, UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine, 27 Bd Jean MOULIN, 13385 Marseille Cedex 5, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Levasseur
authors.affiliation: Aix Marseille Université, URMITE, UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine, 27 Bd Jean MOULIN, 13385 Marseille Cedex 5, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Terras
authors.affiliation: Aix Marseille Université, URMITE, UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine, 27 Bd Jean MOULIN, 13385 Marseille Cedex 5, France.|Aix-Marseille Université, UMR912 SESSTIM (INSERM/IRD/AMU), Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Gaudart
authors.affiliation: Aix Marseille Université, URMITE, UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine, 27 Bd Jean MOULIN, 13385 Marseille Cedex 5, France.
authors.forename: Said
authors.initials: S
authors.lastname: Azza
authors.affiliation: Aix Marseille Université, URMITE, UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine, 27 Bd Jean MOULIN, 13385 Marseille Cedex 5, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Flaudrops
authors.affiliation: Aix Marseille Université, URMITE, UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine, 27 Bd Jean MOULIN, 13385 Marseille Cedex 5, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Robert
authors.affiliation: Aix Marseille Université, URMITE, UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine, 27 Bd Jean MOULIN, 13385 Marseille Cedex 5, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.affiliation: Aix Marseille Université, URMITE, UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine, 27 Bd Jean MOULIN, 13385 Marseille Cedex 5, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Drancourt
mesh_terms: D000352:Africa, Northern / Q000453:epidemiology; D004361:Drug Tolerance; D020869:Gene Expression Profiling; D006801:Humans; D026901:Membrane Transport Proteins / Q000032:analysis / Q000235:genetics; D050296:Microbial Viability / Q000187:drug effects; D010930:Plague / Q000453:epidemiology* / Q000382:microbiology*; D020543:Proteome / Q000032:analysis; D012965:Sodium Chloride / Q000378:metabolism*; D012988:Soil Microbiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D019371:Topography, Medical; D015010:Yersinia pestis / Q000737:chemistry / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*
chemical_list: D026901:Membrane Transport Proteins; D020543:Proteome; D012965:Sodium Chloride