{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:43:36Z","timestamp":1768513416140,"version":"3.49.0"},"posted":{"date-parts":[[2024,6,10]]},"group-title":"Microbiology","reference-count":77,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Borrelia<\/jats:italic>\n                  (or\n                  <jats:italic>Borreliella<\/jats:italic>\n                  )\n                  <jats:italic>burgdorferi<\/jats:italic>\n                  , the causative agent of Lyme disease, is a motile and invasive zoonotic pathogen, adept at navigating between its arthropod vector and mammalian host. While motility and chemotaxis are well established as essential for its enzootic cycle, the function of methyl-accepting chemotaxis proteins (MCPs) in the infectious cycle of\n                  <jats:italic>B. burgdorferi<\/jats:italic>\n                  remains unclear. In this study, we demonstrate that MCP5, one of the most abundant MCPs in\n                  <jats:italic>B. burgdorferi<\/jats:italic>\n                  , is differentially expressed in response to environmental signals as well as at different stages of the pathogen\u2019s enzootic cycle. Specifically, the expression of\n                  <jats:italic>mcp5<\/jats:italic>\n                  is regulated by the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, which are critical for the spirochete\u2019s colonization of the tick vector and mammalian host, respectively. Infection experiments with an\n                  <jats:italic>mcp5<\/jats:italic>\n                  mutant revealed that spirochetes lacking MCP5 could not establish infections in either C3H\/HeN mice or Severe Combined Immunodeficiency (SCID) mice, which are defective in adaptive immunity, indicating the essential role of MCP5 in mammalian infection. However, the\n                  <jats:italic>mcp5<\/jats:italic>\n                  mutant could establish infection and disseminate in NOD SCID Gamma (NSG) mice, which are deficient in both adaptive and most innate immune responses, suggesting a crucial role of MCP5 in evading host innate immunity. In the tick vector, the\n                  <jats:italic>mcp5<\/jats:italic>\n                  mutants survived feeding but failed to transmit to mice, highlighting the importance of MCP5 in transmission. Our findings reveal that MCP5, regulated by the Rrp1 and Rrp2 pathways, is critical for the establishment of infection in mammalian hosts by evading host innate immunity and is important for the transmission of spirochetes from ticks to mammalian hosts, underscoring its potential as a target for intervention strategies.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>SUMMARY<\/jats:title>\n                  <jats:p>\n                    Lyme disease is the most commonly reported arthropod-borne illness in the US, Europe, and Asia. The causative agent of Lyme disease,\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    , is maintained in an enzootic cycle involving arthropod vectors (\n                    <jats:italic>Ixodes<\/jats:italic>\n                    ticks) and rodent mammalian hosts. Understanding how\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    moves within this natural cycle is crucial for developing new strategies to combat Lyme disease. The complex nature of the enzootic cycle necessitates sensory-guided movement in response to environmental stimuli.\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    possesses a unique and intricate chemotaxis signaling system, with methyl-accepting chemotaxis proteins (MCPs) at its core. These proteins are responsible for sensing environmental signals and guiding bacterial movement toward or away from stimuli. This study found that one of the MCPs, MCP5, is highly expressed and differentially regulated during the enzootic cycle by the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways. MCP5 is crucial for mammalian infection, aiding in immune evasion and transmission from ticks to mammals, providing a foundation for further research into\n                    <jats:italic>B. burgdorferi<\/jats:italic>\n                    \u2019s navigation within its hosts.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.06.10.598185","type":"posted-content","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T01:35:12Z","timestamp":1718069712000},"source":"Crossref","is-referenced-by-count":2,"title":["MCP5, a methyl-accepting chemotaxis protein regulated by both the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, is required for the immune evasion of\n                  <i>Borrelia burgdorferi<\/i>"],"prefix":"10.64898","author":[{"given":"Sajith","family":"Raghunandanan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhang","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching Wooen","family":"Sze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raj","family":"Priya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongliang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8234-9991","authenticated-orcid":false,"given":"Brian R","family":"Crane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7231-3167","authenticated-orcid":false,"given":"X. 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