Published April 26, 2025 | Version v2

The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD1 and BICD2 adaptors for dynein-based motility.

  • 1. ROR icon MRC Laboratory of Molecular Biology
  • 2. University of Cambridge
  • 1. ROR icon MRC Laboratory of Molecular Biology
  • 2. ROR icon University of Cambridge
  • 3. Cambridge Institute for Medical Research
  • 4. ROR icon Mahidol Oxford Tropical Medicine Research Unit
  • 5. Mahidol-Oxford Tropical Medicine Research Unit
  • 6. ROR icon Lonza (United States)

Description

The intracellular bacterium Orientia tsutsugamushi relies on the microtubule cytoskeleton and the motor protein dynein to traffic to the perinuclear region within infected cells. However, it remains unclear how the bacterium is coupled to the dynein machinery and how transport is regulated. Here, we discover that O. tsutsugamushi uses its autotransporter protein ScaC to recruit the dynein adaptors BICD1 and BICD2 for movement to the perinucleus. We show that ScaC is sufficient to engage dynein-based motility in the absence of other bacterial proteins and that BICD1 and BICD2 are required for efficient movement of O. tsutsugamushi during infection. Using TIRF single-molecule assays, we demonstrate that ScaC induces BICD2 to adopt an open conformation which activates the assembly of dynein-dynactin complexes. Our results reveal a novel role for BICD adaptors during bacterial infection and provide mechanistic insights into the life cycle of an important human pathogen.

Files

Figure 1.zip

Files (12.7 GB)

Name Size
md5:0cef26e59fb23183258a45bb694b2a2e
2.1 GB Preview Download
md5:63f907b9c53b6a1d541867abc0f8b423
12.8 MB Preview Download
md5:a4b429e3969dcd1431c6ab8c9ab7d748
4.2 GB Preview Download
md5:f5fecb02c011fd5f8c6ea102f5b34c03
4.3 GB Preview Download
md5:3e45ecc90aaadab87337f95afcc06ef9
2.9 MB Preview Download
md5:e95b42d587911759c0ead117609ae89d
1.6 GB Preview Download
md5:ef37a0420a9659a579d32dfa3aabc602
2.5 MB Preview Download
md5:b0b659d80df18a65e133facba562e60e
1.0 MB Preview Download
md5:2cfcaa7e9164000b5d627f8a5c70726d
117.1 kB Preview Download
md5:8bac909b876e08689c1e049c923217b9
563.7 MB Preview Download