Lysozyme Counteracts β-Lactam Antibiotics by Promoting the Emergence of L-Form Bacteria

Kawai, Yoshikazu; Mickiewicz, Katarzyna; Errington, Jeff

doi:10.1016/j.cell.2018.01.021

Cited by 102 publications

(136 citation statements)

References 48 publications

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…Intriguingly, Errington and colleagues have recently shown that B. subtilis can enter into the L‐form state when coping stress inside macrophages and that these bacteria retain viability (Kawai et al, ). Host PG degrading enzymes, like lysozyme and PGLYRP2, are proposed to induce emergence of these cell wall deficient intracellular bacteria (Kawai et al, ). Unlike persistent dormant bacteria, L‐forms grow in the presence of beta‐lactam antibiotics and this is much concern to control bacterial infections.…”

Section: Cell Wall Deficiency In Intracellular Bacteriamentioning

confidence: 99%

“…Work from decades has accumulated evidence supporting the capacity of many bacteria to switch to a physiological state in which they undergo growth and division in the absence of cell wall (Claessen & Errington, 2019). These cell wall deficient bacteria, known as L-forms, have been extensively studied in Gram-positive bacteria like the intracellular pathogen L. monocytogenes (Studer, Borisova, et al, 2016a;Studer, Staubli, et al, 2016) and Bacillus subtilis (Kawai, Mickiewicz, & Errington, 2018). How this physiological state is represented in the adaptation process to the intracellular lifestyle is currently unknown.…”

Section: Cell Wall Defi Cien C Y In Intr Acellul Ar Bac Teriamentioning

confidence: 99%

See 1 more Smart Citation

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

Portillo

2020

Molecular Microbiology

View full text Add to dashboard Cite

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.

show abstract

Section: Cell Wall Deficiency In Intracellular Bacteriamentioning

confidence: 99%

Section: Cell Wall Defi Cien C Y In Intr Acellul Ar Bac Teriamentioning

confidence: 99%

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

Portillo

2020

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

“…It was believed previously that the PBP loss of function was directly bactericidal. PBP inactivation by β‐lactams is seen now as the triggering event that initiates more complex, and perhaps even species‐specific, pathways that culminate in bactericidal cell lysis . Perhaps as a consequence (but at the molecular level, for reasons not understood) some resistance mechanisms against the β‐lactams exert a cellular cost.…”

Section: Miraculous Chemistrymentioning

confidence: 99%

“…PBP inactivation by β-lactams is seen now as the triggering event that initiates more complex, and perhaps even species-specific, pathways that culminate in bactericidal cell lysis. [115][116][117][118][119][120] Perhaps as a consequence (but at the molecular level, for reasons not understood) some resistance mechanisms against the β-lactams exert a cellular cost. The notorious Grampositive pathogen S. aureus does not activate its resistance mechanisms until it detects the presence of a β-lactam.…”

Section: Miraculous Chemistrymentioning

confidence: 99%

Constructing and deconstructing the bacterial cell wall

Fisher

Mobashery

2019

Protein Science

View full text Add to dashboard Cite

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.

show abstract

“…The peptidoglycan layer is also the site of action for antimicrobial agents. Lysozyme, an antimicrobial enzyme critical in animal host defense, is one of the most abundant proteins present on the mucosal surfaces and in body secretions, such as saliva and tears [5, 6]. The epithelial cells secrete lysozyme to protect the host’s mucosal surfaces from infectious bacteria.…”

Section: Introductionmentioning

confidence: 99%

Peptidoglycan layer and disruption processes inBacillus subtiliscells visualized using quick-freeze, deep-etch electron microscopy

Tulum

Tahara

Miyata

2019

Preprint

View full text Add to dashboard Cite

25Peptidoglycan, which is the main component of the bacterial cell wall, is a 26 heterogeneous polymer of glycan strands crosslinked with short peptides and is 27 synthesized in cooperation with the cell division cycle. Although it plays a critical 28 role in bacterial survival, its architecture is not well understood. Herein, we 29 visualized the architecture of the peptidoglycan surface in Bacillus subtilis at the 30 nanometer resolution, using quick-freeze, deep-etch electron microscopy. 31 Filamentous structures were observed on the entire surface of the cell, where 32 filaments about 11-nm wide formed concentric circles on cell poles, filaments 33 about 13-nm wide formed a circumferential mesh-like structure on the cylindrical 34 part, and a "piecrust" structure was observed at the boundary. When growing 35 cells were treated with lysozyme, the entire cell mass migrated to one side and 36 came out from the cell envelope. Fluorescence labeling showed that lysozyme 37 preferentially bound to a cell pole and cell division site, where the peptidoglycan 38 synthesis was not complete. Ruffling of surface structures was observed during 39 electron microscopy. When cells were treated with penicillin, the cell mass came 40 out from a cleft around the cell division site. Outward curvature of the protoplast 41 at the cleft seen using electron microscopy suggested that turgor pressure was 42 applied as the peptidoglycan was not damaged at other positions. When 43 muropeptides were depleted, surface filaments were lost while the rod shape of 44 the cell was maintained. These changes can be explained on the basis of the 45 working points of the chemical structure of peptidoglycan. 46 47 Bacteria, the major inhabitants of the Earth, are in a constant battle to outlast 49 3 their competitors in the environment and the immune system of host organisms. 50 Most bacterial cells are surrounded by a rigid shield called the "peptidoglycan 51 layer," which protects them from chemical agents, including lytic enzymes and 52 antibiotics, that are produced by their competitors [1-4]. 53 Peptidoglycan is an essential component of the bacterial cell wall that is found 54 on the outside of the cytoplasmic membrane of almost all bacterial cells except 55 the class Mollicutes. This polymer provides strength, rigidity, and shape stability 56 by maintaining turgor pressure. In peptidoglycan, the glycan strands comprise 57 alternating β-1,4-linked N-acetylglucosamine (GlcNAc) and N-acetylmuramic 58 acid (MurNAc), and the peptide stems are covalently linked to the glycan 59 strands with an amide bond to the carboxyl carbon of the MurNAc. The 60 peptidoglycan layer is also the site of action for antimicrobial agents. Lysozyme, 61 an antimicrobial enzyme critical in animal host defense, is one of the most 62 abundant proteins present on the mucosal surfaces and in body secretions, 63 such as saliva and tears [5, 6]. The epithelial cells secrete lysozyme to protect 64 the host's mucosal surfaces from infectious bacteria. Lysozyme is also pre...

show abstract

Lysozyme Counteracts β-Lactam Antibiotics by Promoting the Emergence of L-Form Bacteria

Cited by 102 publications

References 48 publications

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

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

Constructing and deconstructing the bacterial cell wall

Peptidoglycan layer and disruption processes inBacillus subtiliscells visualized using quick-freeze, deep-etch electron microscopy

Contact Info

Product

Resources

About