Study of staphylococcal biofilmssearching for new therapeutic targets

  1. Sandra Aguila Arcos
Supervised by:
  1. Itziar Alcorta Calvo Director

Defence university: Universidad del País Vasco - Euskal Herriko Unibertsitatea

Year of defence: 2014

  1. Félix María Goñi Urcelay Chair
  2. Jesús María Arizmendi Bastarrika Secretary
  3. Elisabeth Grohmann Committee member
  4. Maria Victoria Francia Gil Committee member
  5. David Rodríguez Lázaro Committee member

Type: Thesis

Teseo: 116593 DIALNET


Biofilms formed by staphylococci represent one of the major nosocomial infections, especially those related to implanted medical devices. Unfortunately, their inherent resistance to antibiotics makes the treatment of these infections a difficult task. Moreover, they confer an ideal situation for the horizontal gene transfer by bacterial conjugation. This fact allows bacteria to spread antibiotic resistance genes encoded on plasmids. Therefore, knowledge of the factors involved in the biofilm development, as well as identification of DNA molecules responsible for the antibiotic resistance dissemination, could give clues for the search of new therapeutic targets and the production of new drugs against biofilm-associated infections.According to the results obtained in this thesis, the comparative membrane proteome analysis between the commensal strain S. epidermidis CECT 231 grown in biofilm and planktonic conditions revealed that proteins involved in pathogenesis were more abundant in biofilms. In particular, the accumulation associated protein (Aap) seems to be a good candidate as drug target for further investigations. Since S. epidermidis CECT 231 is a non-pathogenic strain, these results also indicate the risk associated with the mode of growth of bacteria and not only to their pathogenic nature.Additionally, conjugative and mobilizable plasmids that codify antibiotic resistance factors were detected in 25 staphylococcal biofilm-forming clinical isolates, and the genes prepT181, aac6-aph2a, ermC and tetK were found as the most prevalent, as well as the sequence oriTpMV158. One of these plasmids (P6) was analysed and it was concluded that this plasmid could be a rolling circle mobilizable plasmid that confers resistance to gentamicin, erythromycin and tetracycline. The characterization of these plasmids could be interesting for designing inhibitors of their transmission and, consequently, to avoid the antibiotic resistance propagation.