Detection of fungal and bacterial carbohydrates: Do the similar structures of chitin and peptidoglycan play a role in immune dysfunction?

Dworkin, Jonathan

doi:10.1371/journal.ppat.1007271

Cited by 10 publications

(7 citation statements)

References 41 publications

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“…This latter possibility seems less likely given that Ile463 is not strongly conserved at this position across LysM domains ( Fig. S5 ) and does not appear to play an important structural role in the LysM domains whose structures have been solved (35).…”

Section: Discussionmentioning

confidence: 99%

SpoIVA-SipL complex formation is essential forClostridioides difficilespore assembly

Touchette

Puebla

Ravichandran

et al. 2019

Preprint

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20Spores are the major infectious particle of the Gram-positive nosocomial pathogen, 21 Clostridioides (formerly Clostridium) difficile, but the molecular details of how this organism 22 forms these metabolically dormant cells remain poorly characterized. The composition of the 23 spore coat in C. difficile differs markedly from that defined in the well-studied organism, 24 Bacillus subtilis, with only 25% of the ~70 spore coat proteins being conserved between the two 25 organisms, and only 2 of 9 coat assembly (morphogenetic) proteins defined in B. subtilis having 26 homologs in C. difficile. We previously identified SipL as a clostridia-specific coat protein 27 essential for functional spore formation. Heterologous expression analyses in E. coli revealed 28 that SipL directly interacts with C. difficile SpoIVA, a coat morphogenetic protein conserved in 29 all spore-forming organisms, through SipL's C-terminal LysM domain. In this study, we show 30 that SpoIVA-SipL binding is essential for C. difficile spore formation and identify specific 31 residues within the LysM domain that stabilize this interaction. Fluorescence microscopy 32 analyses indicate that binding of SipL's LysM domain to SpoIVA is required for SipL to localize 33 to the forespore, while SpoIVA requires SipL to promote encasement of SpoIVA around the 34 forespore. Since we also show that clostridial LysM domains are functionally interchangeable at 35 least in C. difficile, the basic mechanism for SipL-dependent assembly of clostridial spore coats 36 may be conserved. 37 38 39 3 Importance 40 41The metabolically dormant spore-form of the major nosocomial pathogen, Clostridioides 42 difficile, is its major infectious particle. However, the mechanisms controlling the formation of 43 these resistant cell types are not well understood, particularly with respect to its outermost layer, 44 the spore coat. We previously identified two spore morphogenetic proteins in C. difficile: 45 SpoIVA, which is conserved in all spore-forming organisms, and SipL, which is conserved only 46 in the Clostridia. Both SpoIVA and SipL are essential for heat-resistant spore formation and 47 directly interact through SipL's C-terminal LysM domain. In this study, we demonstrate that the 48 LysM domain is critical for SipL and SpoIVA function, likely by helping recruit SipL to the 49 forespore during spore morphogenesis. We further identified residues within the LysM domain 50 that are important for binding SpoIVA and thus functional spore formation. These findings 51 provide important insight into the molecular mechanisms controlling the assembly of infectious 52 C. difficile spores.53 4 Introduction 54 55The Gram-positive pathogen Clostridioides (formerly Clostridium) difficile is a leading 56 cause of antibiotic-associated diarrhea and gastroenteritis in the developed world (1, 2). Since C. 57 difficile is an obligate anaerobe, its major infectious particle is its aerotolerant, metabolically 58 dormant spore form (3, 4). C. difficile spores in the environment ar...

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Section: Discussionmentioning

confidence: 99%

SpoIVA-SipL complex formation is essential forClostridioides difficilespore assembly

Touchette

Puebla

Ravichandran

et al. 2019

Preprint

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“…In plants, the recognition of PG by LysM containing proteins initiates a signaling cascade that can suppress the host immune response (Gust, 2015). Furthermore, several LysM-containing proteins have been described to be involved in diverse processes, including recognition of bacteria, during bacteria-plant symbiosis, bacteriophage infection, and assembly of bacterial spores (Andre et al., 2008; Buist et al., 2008; Zipfel, 2014; Gust, 2015; Dworkin, 2018).…”

Section: Detection Of Released Muropeptidesmentioning

confidence: 99%

Peptidoglycan Muropeptides: Release, Perception, and Functions as Signaling Molecules

2019

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Peptidoglycan (PG) is an essential molecule for the survival of bacteria, and thus, its biosynthesis and remodeling have always been in the spotlight when it comes to the development of antibiotics. The peptidoglycan polymer provides a protective function in bacteria, but at the same time is continuously subjected to editing activities that in some cases lead to the release of peptidoglycan fragments (i.e., muropeptides) to the environment. Several soluble muropeptides have been reported to work as signaling molecules. In this review, we summarize the mechanisms involved in muropeptide release (PG breakdown and PG recycling) and describe the known PG-receptor proteins responsible for PG sensing. Furthermore, we overview the role of muropeptides as signaling molecules, focusing on the microbial responses and their functions in the host beyond their immunostimulatory activity.

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“…The latter possibility seems less likely, given that Ile463 is not strongly conserved at this position across LysM domains (Fig. S5) and does not appear to play an important structural role in the LysM domains whose structures have been solved ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

“…LysM domains frequently bind to N -acetylglucosamine (NAG) residues in chitin (e.g., in eukaryotic LysM domains) and peptidoglycan in prokaryotic LysM-containing proteins ( 35 , 36 ). Recent structural analyses have revealed the molecular basis for LysM binding to peptidoglycan ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

SpoIVA-SipL Complex Formation Is Essential for Clostridioides difficile Spore Assembly

et al. 2019

View full text Add to dashboard Cite

Spores are the major infectious particle of the Gram-positive nosocomial pathogen Clostridioides difficile (formerly Clostridium difficile), but the molecular details of how this organism forms these metabolically dormant cells remain poorly characterized. The composition of the spore coat in C. difficile differs markedly from that defined in the well-studied organism Bacillus subtilis, with only 25% of the ∼70 spore coat proteins being conserved between the two organisms and with only 2 of 9 coat assembly (morphogenetic) proteins defined in B. subtilis having homologs in C. difficile. We previously identified SipL as a clostridium-specific coat protein essential for functional spore formation. Heterologous expression analyses in Escherichia coli revealed that SipL directly interacts with C. difficile SpoIVA, a coat-morphogenetic protein conserved in all spore-forming organisms, through SipL’s C-terminal LysM domain. In this study, we show that SpoIVA-SipL binding is essential for C. difficile spore formation and identify specific residues within the LysM domain that stabilize this interaction. Fluorescence microscopy analyses indicate that binding of SipL’s LysM domain to SpoIVA is required for SipL to localize to the forespore while SpoIVA requires SipL to promote encasement of SpoIVA around the forespore. Since we also show that clostridial LysM domains are functionally interchangeable at least in C. difficile, the basic mechanism for SipL-dependent assembly of clostridial spore coats may be conserved. IMPORTANCE The metabolically dormant spore form of the major nosocomial pathogen Clostridioides difficile is its major infectious particle. However, the mechanisms controlling the formation of this resistant cell type are not well understood, particularly with respect to its outermost layer, the spore coat. We previously identified two spore-morphogenetic proteins in C. difficile: SpoIVA, which is conserved in all spore-forming organisms, and SipL, which is conserved only in the clostridia. Both SpoIVA and SipL are essential for heat-resistant spore formation and directly interact through SipL’s C-terminal LysM domain. In this study, we demonstrate that the LysM domain is critical for SipL and SpoIVA function, likely by helping recruit SipL to the forespore during spore morphogenesis. We further identified residues within the LysM domain that are important for binding SpoIVA and, thus, functional spore formation. These findings provide important insight into the molecular mechanisms controlling the assembly of infectious C. difficile spores.

show abstract

Detection of fungal and bacterial carbohydrates: Do the similar structures of chitin and peptidoglycan play a role in immune dysfunction?

Cited by 10 publications

References 41 publications

SpoIVA-SipL complex formation is essential forClostridioides difficilespore assembly

SpoIVA-SipL complex formation is essential forClostridioides difficilespore assembly

Peptidoglycan Muropeptides: Release, Perception, and Functions as Signaling Molecules

SpoIVA-SipL Complex Formation Is Essential for Clostridioides difficile Spore Assembly

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