Prosthetic joint infections are serious complications that are difficult to treat, which can generate irreversible physical sequelae and high economic costs. Staphylococcus epidermidis is an important commensal in human skin that has had a great impact as an opportunistic pathogen in foreign body related infections. Genes have been described as molecular markers that differentiate infective strains of S. epidermidis from commensal strains. To date, no single marker has been identified to distinguish infective strains from commensal strains of S. epidermidis. In this study, the aim is to identify genetic markers related to the pathogenicity of S. epidermidis that allow discriminating the population of infection and commensal strains. To achieve this objective, 117 strains from 3 populations of S. epidermidis have been studied: 50 strains from patients with joint prosthesis infection (IPA), 50 strains from the skin and nasal swabs of healthy people (PS), and 17 strains of the surgical field during a primary arthroplasty (CQ). The CQ population had not been studied or compared with the other populations. The main objectives were to determine the susceptibility to antibiotics and detect the resistance mechanisms, determine the population structure using pulsed field (PFGE) and multilocus sequence typing (MLST), determine the biofilm formation and detect the genes involved or other elements. Additionally, a whole genome study (WGS) was performed on the ST2 strains. The antibiotic susceptibility study determined high rates of resistance to most of the antibiotics tested, where the IPA strains were the most resistant, followed by the CQ and PS strains. The MLST technique determined in 117 S. epidermidis strains 54 different sequence-type (STs), and 24 STs and 14 new alleles were described for the first time. The ST2 predominated in IPA strains (44%) and was exclusive in this population, followed by ST640 and ST5 (12% both). The PS and CQ strains presented a great variability of STs, without any predominant ST. Most of the strains (68%) were grouped in CC2. The PFGE analysis determined 6 PFGE patterns that included 2-5 strains and 52 unique PFGE patterns. A complementary study was performed by WGS to study the epidemiological relationships through the SNP approach and two possible transmission events from patient to patient were determined. It was not possible to confirm the transmissibility because no clinical-epidemiological relationships were found. All strains were biofilm-producing, suggesting that biofilm formation is not a discriminatory factor for infecting and commensal strains. The genetic content related to biofilm formation varied between different populations of strains. In the IPA strains the sdrF, bhp, the ica operon and the IS256 predominated, and in the commensal strains the embp and hld genes and the mobile element ACME. In conclusion, despite the difficulty of defining the S. epidermidis strains that causing the infection, this study found that the evidence that infectious and commensal strains were not equivalent. No single marker was found to differentiate infection strains from commensal strains, but a combination of several markers allowed us to establish differences between populations. The prosthetic infection strains most frequently belonged to the pathogenic clone ST2 and acquired genetic determinants that promoted infection, such as the ica operon, IS256, sdrF, bhp and mecA. In contrast, commensal strains were characterized by the significant presence of embp, hld, and ACME. WGS is recommended for gene detection and phylogeny studies.
Patogénesis de Staphylococcus epidermidis en la infección de prótesis articular
Sánchez Morillo, A. (Author). 13 Nov 2020
Student thesis: Doctoral thesis
Student thesis: Doctoral thesis