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New targets for combating infections in medical implants

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18.10.2004

Navarre researcher, Jaione Valle Turrillas, has identified two genes that could help as targets for pharmaceutical drugs that fight the Staphylococcus aureus “one of the bacteria which causes most infections in medical implants”. The results of her research have been published in her PhD thesis, "The role of the global regulators SarA and õB in Staphylococcus aureus biofilm formation", defended at the Public University of Navarre.

Bacterias a thousand time more resistant

The bacteria Staphylococcus aureus is one of those which are associated with greater frequency of infections in implants carried out in hospitals. Usually, the bacteria adheres to the surface of the implant, “where microorganism communities are formed that grow on being absorbed into a matrix of polysaccharides, commonly known as biofilm”, according to Jaione Valle.

Once inside this biofilm, the bacteria can be “up to a thousand times more resistant to antibiotic treatments”. Because of this, infections associated with bacterial biofilms are “difficult to eradicate” and, in the majority of cases, “can only be resolved with substitution of the contaminated implant”, she adds.

However, the Navarre biologist has identified two genes “essential for the formation process and maintenance of the biofilm”, that can be used as “promising targets of activity” for new pharmaceutical drugs that “either avoid the forming of the biofilm produced by the said bacteria, or destabilise a biofilm already formed in infections associated with medical implants”.

These are the global regulators SarA and õB. The first is a gene involved in the synthesis of the main exopolysaccharide of the biofilm matrix and, in its absence, “produces a decrease in the amount of exopolysaccharide produced and so the bacteria stops forming biofilm”, the authoress points out.

Moreover, on investigating the role of other regulators in the process of the biofilm formation, it was found that, in the absence of õB, bacteria appear that “had lost their ability to form biofilm”.

Genetics of the biofilm

For the genetic investigation of the process of the biofilm generation, the ability for biofilm formation in clinically isolated strains of S. aureus was analysed first, using a number of laboratory tests. The results of this analysis showed that a high number of analysed strains were able to form biofilm - 80% in fact. Likewise, it was found that biofilm formation with this bacteria “depends on the conditions of the culture used”, Jaione Valle points out.

Of the strains analysed, “clinical strain 15981” was selected as a model bacteria for the molecular study of biofilm formation with S. aureus. Thus, with the aim of identifying the genes involved in the biofilm formation, a collection of 10,000 mutants was generated “in which a transposon provoked, in each of the mutants, the inactivation of a gene in the chromosome in a random manner”, explains the PhD researcher. In this way, the ability to form biofilm in each of the 10,000 mutants was analysed and it was observed that “only three mutants had lost this ability”.

Garazi Andonegi | Source: alphagalileo
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