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Paris, April 2, 2007

How bacteria resist the best-known natural antibacterial : lysozyme

The CNRS Laboratory for Genomic and Structural Information has just elucidated the structure and mechanism of action of a protein used by numerous bacteria to protect themselves from lysozyme. Lysozyme is the first natural antibacterial, and was discovered over eighty-five years ago, in 1921, by Sir Alexander Fleming. The CNRS study is published in the Proceedings of the National Academy of Sciences of the USA, April 3 2007.

In vivo, lysozyme is a small protein present in high concentrations in tears, saliva and the serum of vertebrates.  This protein specifically degrades peptidoglycan, a complex molecule which forms “gram-positive” bacteria cell-walls. Many of these “gram-positive” bacteria are amongst the most common pathogens, such as Staphylococcus, Streptococcus, or the formidable Bacillus anthracis (anthrax). Therefore, lysozyme appears as the first line of defence in vertebrates' anti-infective arsenal.

 

Because every attack triggers a counter-attack in the world of micro-organisms, one would expect that bacteria menaced by lysozyme would develop the means to inhibit its functioning. This prediction was confirmed in 2001 when Chantal Abergel's team from the Laboratory for Genomic and Structural Information (CNRS) discovered the strong anti-lysozyme properties of a protein produced by a gene of the Escherichia coli. This protein was given the name of Ivy (Inhibitor of vertebrate lYsozyme).  In an article in PNAS this team confirmed the protective properties of Ivy as well as the detailed molecular structure of the complex between lysozyme and E. coli's Ivy protein. It is a complex which is also found in E. Coli's distant cousin, the bacteria Pseudomonas aeruginosa.

 

Ivy's three-dimensional structure reveals a type of folding never before described (an increasingly rare discovery) and detail of a small loop of a few amino acids (identically present in related bacteria), which fits, extremely specifically, the active site of lysozyme. This structural information made it possible to look for the presence of an equivalent gene in all known bacterial genomes (almost 500). It was in this way that a veritable family of Ivy proteins was reconstituted, bearing witness to the evolving duel between lysozome and these micro-organisms in a variety of biotopes. A phylogenetic analysis even shows that the gene coding for Ivy was transferred horizontally between certain species of bacteria. This appears to attest to the survival advantage it provides in a natural milieu.

Nevertheless, this study leads us to a new paradox.  Effectively, the Ivy gene is only found in the genomes of so-called “gram-negative” bacteria which are surrounded by a double cell-wall which renders them naturally impermeable and therefore insensitive to lysozyme. None of the numerous genomes of “gram-positive” bacteria, whose cell-walls are lysozyme's usual substrate, contain it. More than eighty years after Fleming's discovery, and countless research projects, the role of lysozyme in controlling bacterial population, though reconfirmed, continues nonetheless to retain a degree of mystery.

image_lysozyme

© Chantal Abergel / CNRS Photothèque (this image is available in the CNRS photo library. Tel: 01 45 07 57 90, phototheque@cnrs-bellevue.fr)

Three-dimensional structure chracteristic of the Ivy protein


References:

Structure and evolution of the Ivy protein family, unexpected lysozyme inhibitors in Gram-negative bacteria, Abergel C, Monchois V, Byrne D,
Chenivesse S, Lembo F, Lazzaroni JC, Claverie JM., Proceedings of the National Academy of Sciences of the USA- avril 2007.

Contact information:

Researcher
Chantal Abergel
T. 04 91 82 54 20
Chantal.Abergel@igs.cnrs-mrs.fr

Media relations
Cécile Pérol
T. 01 44 96 43 09
cecile.perol@cnrs-dir.fr


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