Lytic transglycosylases: concinnity in concision of the bacterial cell wall

Dik, David A.; Marous, Daniel R.; Fisher, Jed F.; Mobashery, Shahriar

doi:10.1080/10409238.2017.1337705

Cited by 134 publications

(203 citation statements)

References 300 publications

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“…Addition of 0.2% glucose could not phenotypically suppress MltE complementation of the ∆2 LTG mutant chaining defect (data not shown), suggesting that perhaps leaky expression from P tac (Rosano and Ceccarelli, ) is sufficient for supporting cell separation. MltE has a relatively broad spectrum of PG substrate specificity, shown in vitro to generate products indicative of both endo‐ and exolytic cleavage on denuded or un‐crosslinked muropeptides (Lee et al , ; Dik et al , ; Byun et al , ), and has no known homolog in V. cholerae. Overexpression of mltE was not toxic in a WT background, suggesting that it primarily digests septal PG in the V. cholerae ∆2 LTG mutant (Fig. )…”

Section: Resultsmentioning

confidence: 99%

“…. MltE has a strong preference for uncrosslinked PG (Lee et al , ; Dik et al , ; Byun et al , ), providing a possible explanation for its lack of general toxicity, since the main body of the cell’s PG is generally crosslinked (Desmarais et al , ). Incidentally, this also suggests that septal PG in ∆2 LTG is largely uncrosslinked; which would be consistent with completed or concurrent amidase or endopeptidase activity.…”

Section: Resultsmentioning

confidence: 99%

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

Weaver

Jiménez-Ruiz

Tallavajhala

et al. 2019

Molecular Microbiology

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Summary The cell wall is a crucial structural feature in the vast majority of bacteria and comprises a covalently closed network of peptidoglycan (PG) strands. While PG synthesis is important for survival under many conditions, the cell wall is also a dynamic structure, undergoing degradation and remodeling by ‘autolysins’, enzymes that break down PG. Cell division, for example, requires extensive PG remodeling, especially during separation of daughter cells, which depends heavily upon the activity of amidases. However, in Vibrio cholerae, we demonstrate that amidase activity alone is insufficient for daughter cell separation and that lytic transglycosylases RlpA and MltC both contribute to this process. MltC and RlpA both localize to the septum and are functionally redundant under normal laboratory conditions; however, only RlpA can support normal cell separation in low‐salt media. The division‐specific activity of lytic transglycosylases has implications for the local structure of septal PG, suggesting that there may be glycan bridges between daughter cells that cannot be resolved by amidases. We propose that lytic transglycosylases at the septum cleave PG strands that are crosslinked beyond the reach of the highly regulated activity of the amidase and clear PG debris that may block the completion of outer membrane invagination.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Weaver

Jiménez-Ruiz

Tallavajhala

et al. 2019

Molecular Microbiology

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“…MltB, a member of the lytic transglycosylase (LT) family, cleaves the glycosidic bond between N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) residues of peptidoglycan (PG), concommittantly forming a 1,6-anhydro bond in the MurNAc residue (Dik et al, 2017;Höltje et al, 1975;Scheurwater et al, 2008). These enzymes are involved in remodeling of the PG layer and releasing PG fragments (1,6-anhydro-muropeptides), and consequently, important for cell wall integrity (Dik et al, 2017). Recently, it was shown that LTs are important for pathogenesis in Neisseria gonorrhoeae, Brucella abortus and Edwardsiella tarda (Bao et al, 2017;Knilans et al, 2017;Liu et al, 2012;Ragland et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

The lytic transglycosylase MltB connects membrane homeostasis and in vivo fitness of Acinetobacter baumannii

Crépin

Ottosen

Peters

et al. 2018

Molecular Microbiology

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SUMMARY Acinetobacter baumannii has emerged as a leading nosocomial pathogen, infecting a wide range of anatomic sites including the respiratory tract and the bloodstream. In addition to being multi-drug resistant, little is known about the molecular basis of A. baumannii pathogenesis. To better understand A. baumannii virulence, a combination of a transposon-sequencing (TraDIS) screen and the neutropenic mouse model of bacteremia was used to identify the full set of fitness genes required during bloodstream infection. The lytic transglycosylase MltB was identified as a critical fitness factor. MltB cleaves the MurNAc-GlcNAc bond of peptidoglycan, which leads to cell wall remodeling. Here we show that MltB is part of a complex network connecting resistance to stresses, membrane homeostasis, biogenesis of pili and in vivo fitness. Indeed, inactivation of mltB not only impaired resistance to serum complement, cationic antimicrobial peptides and oxygen species, but also altered the cell envelope integrity, activated the envelope stress response, drastically reduced the number of pili at the cell surface and finally, significantly decreased colonization of both the bloodstream and the respiratory tract.

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“…The breadth of study of this β‐lactamase‐resistance response—from the molecular (antibiotic structure) to the macromolecular (protein‐ligand interaction, biochemical pathways) to the microbiological and the clinical—requires the medium of the comprehensive review . Here, we focus on the involvement of a family of important enzymes—the lytic transglycosylases—in peptidoglycan recycling and β‐lactamase induction …”

Section: Abetting the β‐Lactam Antibiotics Against Gram‐negative Bactmentioning

confidence: 99%

“…[221][222][223][224][225][226][227][228] Here, we focus on the involvement of a family of important enzymes-the lytic transglycosylases-in peptidoglycan recycling and β-lactamase induction. 229,230 The lytic transglycosylases (LTs) are periplasmic enzymes (many, but not all, lipoproteins) that catalyze the deconstruction (hence "lytic") of the polymeric peptidoglycan through the nonhydrolytic cleavage of the glycan strand of the peptidoglycan (hence, the awkward "transglycosylase"). Among the ensemble of cell-wall deconstructing enzymes that are found in the periplasm, 98,231,232 the lytic transglycosylases have a central position both with respect to key pathways and events.…”

Section: Abetting the β-Lactam Antibiotics Against Gram-negative Bamentioning

confidence: 99%

Constructing and deconstructing the bacterial cell wall

Fisher

Mobashery

2019

Protein Science

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The history of modern medicine cannot be written apart from the history of the antibiotics. Antibiotics are cytotoxic secondary metabolites that are isolated from Nature. The antibacterial antibiotics disproportionately target bacterial protein structure that is distinct from eukaryotic protein structure, notably within the ribosome and within the pathways for bacterial cell‐wall biosynthesis (for which there is not a eukaryotic counterpart). This review focuses on a pre‐eminent class of antibiotics—the β‐lactams, exemplified by the penicillins and cephalosporins—from the perspective of the evolving mechanisms for bacterial resistance. The mechanism of action of the β‐lactams is bacterial cell‐wall destruction. In the monoderm (single membrane, Gram‐positive staining) pathogen Staphylococcus aureus the dominant resistance mechanism is expression of a β‐lactam‐unreactive transpeptidase enzyme that functions in cell‐wall construction. In the diderm (dual membrane, Gram‐negative staining) pathogen Pseudomonas aeruginosa a dominant resistance mechanism (among several) is expression of a hydrolytic enzyme that destroys the critical β‐lactam ring of the antibiotic. The key sensing mechanism used by P. aeruginosa is monitoring the molecular difference between cell‐wall construction and cell‐wall deconstruction. In both bacteria, the resistance pathways are manifested only when the bacteria detect the presence of β‐lactams. This review summarizes how the β‐lactams are sensed and how the resistance mechanisms are manifested, with the expectation that preventing these processes will be critical to future chemotherapeutic control of multidrug resistant bacteria.

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Lytic transglycosylases: concinnity in concision of the bacterial cell wall

Cited by 134 publications

References 300 publications

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

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

The lytic transglycosylase MltB connects membrane homeostasis and in vivo fitness of Acinetobacter baumannii

Constructing and deconstructing the bacterial cell wall

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