Effect of alanine ester substitution and other structural features of lipoteichoic acids on their inhibitory activity against autolysins of Staphylococcus aureus

Fischer, Werner; Rösel, Peter; Koch, Hans-Georg

doi:10.1128/jb.146.2.467-475.1981

Cited by 126 publications

(39 citation statements)

References 35 publications

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“…Lipoteichoic acids directly modulate the activity of many autolysins -repressing some and activating others (Fischer et al, 1981;Bierbaum and Sahl, 1987;Smith et al, 2000;Fedtke et al, 2007). Auto activity may also directly be regulated by LTA.…”

Section: Role Of the Gw Domainsmentioning

confidence: 99%

Structural basis for autoinhibition and activation of Auto, a virulence‐associated peptidoglycan hydrolase of Listeria monocytogenes

Bublitz

Polle

Holland

et al. 2009

Molecular Microbiology

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SummaryDuring a bacterial infection, each successive step is orchestrated by a dedicated set of virulence factors. In Gram-positive bacteria, the presentation or release of such factors is crucially dependent on the continual remodelling of the cell wall. We have investigated the autolysin or peptidoglycan hydrolase Auto (Lmo1076) from the human pathogen Listeria monocytogenes to structurally and biochemically underpin its role in host cell invasion. We demonstrate that Auto is an N-acetylglucosaminidase, that it is autoinhibited when newly secreted but activated by proteolytic cleavage, that it has an acidic pH optimum and that it preferentially cleaves acetylated over de-acetylated peptidoglycan. The crystal structure of Auto, the first for glycoside hydrolase family 73, and the first for a listerial autolysin, indicates that autoinhibition is due to an N-terminal a-helix unique to Auto that physically blocks the substrate-binding cleft. We identify Glu122 and Glu156 as the two catalytically essential carboxylate groups. The physical properties of Auto as well as its localization to lipoteichoic acid by its four C-terminal GW modules imply cell wall degradation by Auto to be highly co-ordinated. Its spatio-temporally controlled activation and localized activity in an acidified environment indicate that it facilitates remodelling of the cell wall and may be involved in co-ordinating the release of virulence factors at specific stages of an infection.

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Section: Role Of the Gw Domainsmentioning

confidence: 99%

Structural basis for autoinhibition and activation of Auto, a virulence‐associated peptidoglycan hydrolase of Listeria monocytogenes

Bublitz

Polle

Holland

et al. 2009

Molecular Microbiology

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“…Nevertheless, LTA derived from Streptococcus mutans but neither deacylated LTA nor teichoic acid, inhibited polycation‐induced bacteriolysis by acting directly on the muramidases (46). The inhibitory effect of LTA on the autolysins was found to reside in a sequence of glycerophosphate units, and it was deduced that the negative charges of appropriately spaced phosphodiester groups could play a crucial role in its inhibitory effect (45).…”

Section: Lta and Phospholipids May Deregulate The Autolytic Systemsmentioning

confidence: 99%

“…How then can the synergism among microbial and host‐derived agonists be controlled at the bedside? (1–3, 13–55, 23, 105).…”

Section: Possible Therapeutic Strategiesmentioning

confidence: 99%

The role of bacteriolysis in the pathophysiology of inflammation, infection and post‐infectious sequelae

Ginsburg

2002

APMIS

114

102

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The literature dealing with the biochemical basis of bacteriolysis and its role in inflammation, infection and in post-infectious sequelae is reviewed and discussed. Bacteriolysis is an event that may occur when normal microbial multiplication is altered due to an uncontrolled activation of a series of autolytic cell-wall breaking enzymes (muramidases). While a low-level bacteriolysis sometimes occurs physiologically, due to "mistakes" in cell separation, a pronounced cell wall breakdown may occur following bacteriolysis induced either by beta-lactam antibiotics or by a large variety of bacteriolysis-inducing cationic peptides. These include spermine, spermidine, bactericidal peptides defensins, bacterial permeability increasing peptides from neutrophils, cationic proteins from eosinophils, lysozyme, myeloperoxidase, lactoferrin, the highly cationic proteinases elastase and cathepsins, PLA2, and certain synthetic polyamino acids. The cationic agents probably function by deregulating lipoteichoic acid (LTA) in Gram-positive bacteria and phospholipids in Gram-negative bacteria, the presumed regulators of the autolytic enzyme systems (muramidases). When bacteriolysis occurs in vivo, cell-wall- and -membrane-associated lipopolysaccharide (LPS (endotoxin)), lipoteichoic acid (LTA) and peptidoglycan (PPG), are released. These highly phlogistic agents can act on macrophages, either individually or in synergy, to induce the generation and release of reactive oxygen and nitrogen species, cytotoxic cytokines, hydrolases, proteinases, and also to activate the coagulation and complement cascades. All these agents and processes are involved in the pathophysiology of septic shock and multiple organ failure resulting from severe microbial infections. Bacteriolysis induced in in vitro models, either by polycations or by beta-lactams, could be effectively inhibited by sulfated polysaccharides, by D-amino acids as well as by certain anti-bacteriolytic antibiotics. However, within phagocytic cells in inflammatory sites, bacteriolysis tends to be strongly inhibited presumably due to the inactivation by oxidants and proteinases of the bacterial muramidases. This might results in a long persistence of non-biodegradable cell-wall components causing granulomatous inflammation. However, persistence of microbial cell walls in vivo may also boost innate immunity against infections and against tumor-cell proliferation. Therapeutic strategies to cope with the deleterious effects of bacteriolysis in vivo include combinations of autolysin inhibitors with combinations of certain anti-inflammatory agents. These might inhibit the synergistic tissue- and- organ-damaging "cross talks" which lead to septic shock and to additional post-infectious sequelae.

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“…U waŝ hypothesized that the observed increase in chain length could be caused by increased celJ-to-cell adhesion or the re-"loval of a fector that promotes dechaining. Other studies have indicated that wall components such as lipoteichoic acids may also play a role in cell division and separation (3,7,9,17).…”

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confidence: 99%

Chain formation and de‐chaining in Streptococcus sobrinus SL‐1

Thibodeau

Ford

1991

Oral Microbiology and Immunology

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Regulation of chain length by chain-forming bacteria is believed to depend on wall-associated autolytic activity and environmental conditions. In this study, the chain length of Streptococcus sobrinus SL-1 was determined under various initial culture and pH conditions and NaF concentrations. Crude wall extracts were prepared by dilute alkali treatment of whole cells and were tested for de-chaining activity. The results indicate that S. sobrinus SL-1 grows primarily as short chains under alkaline growth conditions and at high (3.0 mM) medium fluoride levels, and growth as long chains occurs under acidic growth conditions. De-chaining activity was observed following incubation of the longer chain form of the organism with crude wall extracts. The evidence suggests that the chain length of S. sobrinus SL-1 depends on environmental conditions, including pH and fluoride, and that cell wall-associated factors may be active in regulating the chain length of the organism.

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Effect of alanine ester substitution and other structural features of lipoteichoic acids on their inhibitory activity against autolysins of Staphylococcus aureus

Cited by 126 publications

References 35 publications

Structural basis for autoinhibition and activation of Auto, a virulence‐associated peptidoglycan hydrolase of Listeria monocytogenes

Structural basis for autoinhibition and activation of Auto, a virulence‐associated peptidoglycan hydrolase of Listeria monocytogenes

The role of bacteriolysis in the pathophysiology of inflammation, infection and post‐infectious sequelae

Chain formation and de‐chaining in Streptococcus sobrinus SL‐1

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