PMID- 38238469 OWN - NLM STAT- MEDLINE DCOM- 20240208 LR - 20240329 IS - 2058-5276 (Electronic) IS - 2058-5276 (Linking) VI - 9 IP - 2 DP - 2024 Feb TI - Yersinia entomophaga Tc toxin is released by T10SS-dependent lysis of specialized cell subpopulations. PG - 390-404 LID - 10.1038/s41564-023-01571-z [doi] AB - Disease-causing bacteria secrete numerous toxins to invade and subjugate their hosts. Unlike many smaller toxins, the secretion machinery of most large toxins remains enigmatic. By combining genomic editing, proteomic profiling and cryo-electron tomography of the insect pathogen Yersinia entomophaga, we demonstrate that a specialized subset of these cells produces a complex toxin cocktail, including the nearly ribosome-sized Tc toxin YenTc, which is subsequently exported by controlled cell lysis using a transcriptionally coupled, pH-dependent type 10 secretion system (T10SS). Our results dissect the Tc toxin export process by a T10SS, identifying that T10SSs operate via a previously unknown lytic mode of action and establishing them as crucial players in the size-insensitive release of cytoplasmically folded toxins. With T10SSs directly embedded in Tc toxin operons of major pathogens, we anticipate that our findings may model an important aspect of pathogenesis in bacteria with substantial impact on agriculture and healthcare. CI - (c) 2024. The Author(s). FAU - Sitsel, Oleg AU - Sitsel O AUID- ORCID: 0000-0002-4496-7489 AD - Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany. FAU - Wang, Zhexin AU - Wang Z AUID- ORCID: 0000-0002-4256-1143 AD - Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany. FAU - Janning, Petra AU - Janning P AD - Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany. FAU - Kroczek, Lara AU - Kroczek L AD - Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany. FAU - Wagner, Thorsten AU - Wagner T AD - Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany. FAU - Raunser, Stefan AU - Raunser S AUID- ORCID: 0000-0001-9373-3016 AD - Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany. stefan.raunser@mpi-dortmund.mpg.de. LA - eng PT - Journal Article DEP - 20240118 PL - England TA - Nat Microbiol JT - Nature microbiology JID - 101674869 RN - Yersinia entomophaga SB - IM MH - *Proteomics MH - *Yersinia/genetics/metabolism PMC - PMC10847048 COIS- O.S. and S.R. are inventors on a filed patent application (PCT/EP2023/074766) for producing insecticidal toxins using the described bacterial strains. The remaining authors declare no competing interests. EDAT- 2024/01/19 00:42 MHDA- 2024/02/08 06:42 PMCR- 2024/01/18 CRDT- 2024/01/18 23:23 PHST- 2023/03/28 00:00 [received] PHST- 2023/11/29 00:00 [accepted] PHST- 2024/02/08 06:42 [medline] PHST- 2024/01/19 00:42 [pubmed] PHST- 2024/01/18 23:23 [entrez] PHST- 2024/01/18 00:00 [pmc-release] AID - 10.1038/s41564-023-01571-z [pii] AID - 1571 [pii] AID - 10.1038/s41564-023-01571-z [doi] PST - ppublish SO - Nat Microbiol. 2024 Feb;9(2):390-404. doi: 10.1038/s41564-023-01571-z. Epub 2024 Jan 18.