SpoIIIL is a forespore factor required for efficient cell-cell signalling during Bacillus subtilis sporulation.

During endospore formation, the mother cell and developing spore establish cell-cell signalling pathways that lead to compartment-specific transcription and key steps in morphogenesis. Endospore-forming bacteria also assemble a highly conserved essential membrane complex, called the A-Q complex, tha...

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Main Authors: Danae Morales Angeles, Kaitlyn Coleman, Chimezie Progress Odika, Chris L B Graham, Helena Chan, Michael Gilmore, Najwa Taib, Elda Bauda, Christine Moriscot, Benoit Gallet, Hannah Fisher, Per A Bullough, Cécile Morlot, Darius Köster, Simonetta Gribaldo, Felipe Cava, Christopher D A Rodrigues
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-07-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1011768
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author Danae Morales Angeles
Kaitlyn Coleman
Chimezie Progress Odika
Chris L B Graham
Helena Chan
Michael Gilmore
Najwa Taib
Elda Bauda
Christine Moriscot
Benoit Gallet
Hannah Fisher
Per A Bullough
Cécile Morlot
Darius Köster
Simonetta Gribaldo
Felipe Cava
Christopher D A Rodrigues
author_facet Danae Morales Angeles
Kaitlyn Coleman
Chimezie Progress Odika
Chris L B Graham
Helena Chan
Michael Gilmore
Najwa Taib
Elda Bauda
Christine Moriscot
Benoit Gallet
Hannah Fisher
Per A Bullough
Cécile Morlot
Darius Köster
Simonetta Gribaldo
Felipe Cava
Christopher D A Rodrigues
author_sort Danae Morales Angeles
collection DOAJ
description During endospore formation, the mother cell and developing spore establish cell-cell signalling pathways that lead to compartment-specific transcription and key steps in morphogenesis. Endospore-forming bacteria also assemble a highly conserved essential membrane complex, called the A-Q complex, that physically connects these cells and may serve as a molecular conduit between them. While SpoIIIL was previously identified as a putative A-Q complex component in Bacillus subtilis, its exact role remains unclear. Here, we found that SpoIIIL does not function in the A-Q complex but instead acts as a forespore-specific factor required for efficient cell-cell signalling that leads to late mother cell transcription. Quantitative image analysis revealed that spoIIIL mutant spores do not exhibit hallmark phenotypes of A-Q complex mutants. Furthermore, unlike well-characterized A-Q complex proteins, SpoIIIL-GFP localizes uniformly in the forespore membrane before dispersing into the forespore cytoplasm. A synthetic sporulation screen identified a genetic relationship between spoIIIL and murAB, a paralog of murAA, required for efficient peptidoglycan precursor synthesis during sporulation. Cytological analysis indicates that the spoIIIL murAB double mutant is severely defective in the assembly of spore cortex peptidoglycan. Investigations into how SpoIIIL affects the cortex suggest it contributes to the activity of SpoIVB, a secreted forespore protease that initiates the signalling pathway required for processing of inactive pro-σK to active σK in the mother cell, which in turn up-regulates peptidoglycan precursor synthesis required for cortex formation. Accordingly, the spoIIIL mutant exhibits delayed and reduced pro-σK processing and decreased accumulation of peptidoglycan precursors. Thus, cortex assembly defects in the spoIIIL murAB double mutant results from alterations in separate pathways contributing to peptidoglycan precursor synthesis. Finally, phylogenetic analyses reveal that SpoIIIL is restricted to a subset of Bacillales species, highlighting evolutionary specialization in the signalling pathway leading to σK activation. Collectively, our findings redefine SpoIIIL as a forespore factor required for efficient cell-cell signalling that controls late mother-cell transcription.
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spelling doaj-art-85dfcdd0a5e744d18bbcd23b8f21c22d2025-08-20T03:13:30ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-07-01217e101176810.1371/journal.pgen.1011768SpoIIIL is a forespore factor required for efficient cell-cell signalling during Bacillus subtilis sporulation.Danae Morales AngelesKaitlyn ColemanChimezie Progress OdikaChris L B GrahamHelena ChanMichael GilmoreNajwa TaibElda BaudaChristine MoriscotBenoit GalletHannah FisherPer A BulloughCécile MorlotDarius KösterSimonetta GribaldoFelipe CavaChristopher D A RodriguesDuring endospore formation, the mother cell and developing spore establish cell-cell signalling pathways that lead to compartment-specific transcription and key steps in morphogenesis. Endospore-forming bacteria also assemble a highly conserved essential membrane complex, called the A-Q complex, that physically connects these cells and may serve as a molecular conduit between them. While SpoIIIL was previously identified as a putative A-Q complex component in Bacillus subtilis, its exact role remains unclear. Here, we found that SpoIIIL does not function in the A-Q complex but instead acts as a forespore-specific factor required for efficient cell-cell signalling that leads to late mother cell transcription. Quantitative image analysis revealed that spoIIIL mutant spores do not exhibit hallmark phenotypes of A-Q complex mutants. Furthermore, unlike well-characterized A-Q complex proteins, SpoIIIL-GFP localizes uniformly in the forespore membrane before dispersing into the forespore cytoplasm. A synthetic sporulation screen identified a genetic relationship between spoIIIL and murAB, a paralog of murAA, required for efficient peptidoglycan precursor synthesis during sporulation. Cytological analysis indicates that the spoIIIL murAB double mutant is severely defective in the assembly of spore cortex peptidoglycan. Investigations into how SpoIIIL affects the cortex suggest it contributes to the activity of SpoIVB, a secreted forespore protease that initiates the signalling pathway required for processing of inactive pro-σK to active σK in the mother cell, which in turn up-regulates peptidoglycan precursor synthesis required for cortex formation. Accordingly, the spoIIIL mutant exhibits delayed and reduced pro-σK processing and decreased accumulation of peptidoglycan precursors. Thus, cortex assembly defects in the spoIIIL murAB double mutant results from alterations in separate pathways contributing to peptidoglycan precursor synthesis. Finally, phylogenetic analyses reveal that SpoIIIL is restricted to a subset of Bacillales species, highlighting evolutionary specialization in the signalling pathway leading to σK activation. Collectively, our findings redefine SpoIIIL as a forespore factor required for efficient cell-cell signalling that controls late mother-cell transcription.https://doi.org/10.1371/journal.pgen.1011768
spellingShingle Danae Morales Angeles
Kaitlyn Coleman
Chimezie Progress Odika
Chris L B Graham
Helena Chan
Michael Gilmore
Najwa Taib
Elda Bauda
Christine Moriscot
Benoit Gallet
Hannah Fisher
Per A Bullough
Cécile Morlot
Darius Köster
Simonetta Gribaldo
Felipe Cava
Christopher D A Rodrigues
SpoIIIL is a forespore factor required for efficient cell-cell signalling during Bacillus subtilis sporulation.
PLoS Genetics
title SpoIIIL is a forespore factor required for efficient cell-cell signalling during Bacillus subtilis sporulation.
title_full SpoIIIL is a forespore factor required for efficient cell-cell signalling during Bacillus subtilis sporulation.
title_fullStr SpoIIIL is a forespore factor required for efficient cell-cell signalling during Bacillus subtilis sporulation.
title_full_unstemmed SpoIIIL is a forespore factor required for efficient cell-cell signalling during Bacillus subtilis sporulation.
title_short SpoIIIL is a forespore factor required for efficient cell-cell signalling during Bacillus subtilis sporulation.
title_sort spoiiil is a forespore factor required for efficient cell cell signalling during bacillus subtilis sporulation
url https://doi.org/10.1371/journal.pgen.1011768
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