Lytic transglycosylases RlpA and MltC assist in <i>Vibrio cholerae</i> daughter cell separation

Weaver, Anna; Jiménez-Ruiz, Valeria; Tallavajhala, Srikar; Ransegnola, Brett; Wong, Kimberly; Dörr, Tobias

doi:10.1111/mmi.14349

Cited by 34 publications

(53 citation statements)

References 80 publications

(129 reference statements)

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“…Denuded glycans are known to pose a significant impediment to the completion of cell division based on results from Pseudomonas aeruginosa, where inactivation of RlpA, a denuded glycan-specific LT, was shown to cause a cell chaining phenotype (34). From these results, we conclude that amidase activation remains functional when Tol-Pal is inactivated, but that the denuded glycan products produced are not efficiently processed and impair cell separation, presumably because they remain anchored at each end to opposite daughter poles (40). Thus, the chaining phenotype of tol-pal mutants cannot simply be interpreted as a defect in OM constriction.…”

Section: Discussionmentioning

confidence: 83%

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The Tol-Pal system is required for peptidoglycan-cleaving enzymes to complete bacterial cell division

Yakhnina

Bernhardt

2020

Proc. Natl. Acad. Sci. U.S.A.

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Tol-Pal is a multiprotein system present in the envelope of Gram-negative bacteria. Inactivation of this widely conserved machinery compromises the outer membrane (OM) layer of these organisms, resulting in hypersensitivity to many antibiotics. Mutants in thetol-pallocus fail to complete division and form cell chains. This phenotype along with the localization of Tol-Pal components to the cytokinetic ring inEscherichia colihas led to the proposal that the primary function of the system is to promote OM constriction during division. Accordingly, a poorly constricted OM is believed to link the cell chains formed upon Tol-Pal inactivation. However, we show here that cell chains ofE. coli tol-palmutants are connected by an incompletely processed peptidoglycan (PG) layer. Genetic suppressors of this defect were isolated and found to overproduce OM lipoproteins capable of cleaving the glycan strands of PG. Among the factors promoting cell separation in mutant cells was a protein of previously unknown function (YddW), which we have identified as a divisome-localized glycosyl hydrolase that cleaves peptide-free PG glycans. Overall, our results indicate that the cell chaining defect of Tol-Pal mutants cannot simply be interpreted as a defect in OM constriction. Rather, the complex also appears to be required for the activity of several OM-localized enzymes with cell wall remodeling activity. Thus, the Tol-Pal system may play a more general role in coordinating OM invagination with PG remodeling at the division site than previously appreciated.

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Section: Discussionmentioning

confidence: 83%

“…In E. coli and Vibrio cholerae, the deletion of multiple LTencoding genes is required to generate a chaining phenotype that resembles the severity of the defect caused by inactivating Tol-Pal in these organisms (40,41). Also, the inactivation of several LT enzymes in P. aeruginosa was found to compromise the OM permeability barrier (42).…”

Section: Discussionmentioning

confidence: 99%

The Tol-Pal system is required for peptidoglycan-cleaving enzymes to complete bacterial cell division

Yakhnina

Bernhardt

2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Cell separation in E. coli is primarily achieved through the combined activity of three LytC-type N -acetylmuramoyl- l- alanine amidases (AmiA, AmiB, and AmiC), which cleave the peptide stem from the glycan backbone of PG to produce stemless (“denuded”) glycans ( 39 , 40 ). Certain endopeptidases and lytic transglycosylases may also assist in cell separation ( 41 – 43 ).…”

Section: Peptidoglycan Metabolismmentioning

confidence: 99%

Bacterial Cell Wall Quality Control during Environmental Stress

Mueller

Levin

2020

mBio

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Single-celled organisms must adapt their physiology to persist and propagate across a wide range of environmental conditions. The growth and division of bacterial cells depend on continuous synthesis of an essential extracellular barrier: the peptidoglycan cell wall, a polysaccharide matrix that counteracts turgor pressure and confers cell shape. Unlike many other essential processes and structures within the bacterial cell, the peptidoglycan cell wall and its synthesis machinery reside at the cell surface and are thus uniquely vulnerable to the physicochemical environment and exogenous threats. In addition to the diversity of stressors endangering cell wall integrity, defects in peptidoglycan metabolism require rapid repair in order to prevent osmotic lysis, which can occur within minutes. Here, we review recent work that illuminates mechanisms that ensure robust peptidoglycan metabolism in response to persistent and acute environmental stress. Advances in our understanding of bacterial cell wall quality control promise to inform the development and use of antimicrobial agents that target the synthesis and remodeling of this essential macromolecule. IMPORTANCE Nearly all bacteria are encased in a peptidoglycan cell wall, an essential polysaccharide structure that protects the cell from osmotic rupture and reinforces cell shape. The integrity of this protective barrier must be maintained across the diversity of environmental conditions wherein bacteria replicate. However, at the cell surface, the cell wall and its synthesis machinery face unique challenges that threaten their integrity. Directly exposed to the extracellular environment, the peptidoglycan synthesis machinery encounters dynamic and extreme physicochemical conditions, which may impair enzymatic activity and critical protein-protein interactions. Biotic and abiotic stressors—including host defenses, cell wall active antibiotics, and predatory bacteria and phage—also jeopardize peptidoglycan integrity by introducing lesions, which must be rapidly repaired to prevent cell lysis. Here, we review recently discovered mechanisms that promote robust peptidoglycan synthesis during environmental and acute stress and highlight the opportunities and challenges for the development of cell wall active therapeutics.

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“…The mutant carrying the minimal PG biosynthesis machinery does not show a growth phenotype in laboratory media, however it is impaired for virulence and become highly susceptible to antibiotics (Reed et al, ). Another case of enzyme specialization includes the lytic transglycosylase RlpA, which is absolutely required for separation of Vibrio cholerae cells in low salt medium (Weaver et al, ). A lesson to learn from these studies is that restricting the study of PG metabolism to laboratory conditions can hide the action of defined enzymes or structural variations in the PG that might be relevant in other, more natural niches.…”

Section: Redundancy and Specialization Of Pg Enzymes In Intracellularmentioning

confidence: 99%

Building peptidoglycan inside eukaryotic cells: A view from symbiotic and pathogenic bacteria

Portillo

2020

Molecular Microbiology

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The peptidoglycan (PG), as the exoskeleton of most prokaryotes, maintains a defined shape and ensures cell integrity against the high internal turgor pressure. These important roles have attracted researchers to target PG metabolism in order to control bacterial infections. Most studies, however, have been performed in bacteria grown under laboratory conditions, leading to only a partial view on how the PG is synthetized in natural environments. As a case in point, PG metabolism and its regulation remain poorly understood in symbiotic and pathogenic bacteria living inside eukaryotic cells. This review focuses on the PG metabolism of intracellular bacteria, emphasizing the necessity of more in vivo studies involving the analysis of enzymes produced in the intracellular niche and the isolation of PG from bacteria residing within eukaryotic cells. The review also points to persistent infections caused by some intracellular bacterial pathogens and the extent at which the PG could contribute to establish such physiological state. Based on recent evidences, I speculate on the idea that certain structural features of the PG may facilitate attenuation of intracellular growth. Lastly, I discuss recent findings in endosymbionts supporting a cooperation between host and bacterial enzymes to assemble a mature PG.

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Lytic transglycosylases RlpA and MltC assist in Vibrio cholerae daughter cell separation

Cited by 34 publications

References 80 publications

The Tol-Pal system is required for peptidoglycan-cleaving enzymes to complete bacterial cell division

The Tol-Pal system is required for peptidoglycan-cleaving enzymes to complete bacterial cell division

Bacterial Cell Wall Quality Control during Environmental Stress

Building peptidoglycan inside eukaryotic cells: A view from symbiotic and pathogenic bacteria

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