Biofilm is a Major Virulence Determinant in Bacterial Colonization of Chronic Skin Ulcers Independently from the Multidrug Resistant Phenotype.

Bacterial biofilm is a major factor in delayed wound healing and high levels of biofilm production have been repeatedly described in multidrug resistant organisms (MDROs). Nevertheless, a quantitative correlation between biofilm production and the profile of antimicrobial drug resistance in delayed wound healing remains to be determined. Microbial identification, antibiotic susceptibility and biofilm production were assessed in 135 clinical isolates from 87 patients. Gram-negative bacteria were the most represented microorganisms (60.8%) with MDROs accounting for 31.8% of the total isolates. Assessment of biofilm production revealed that 80% of the strains were able to form biofilm. A comparable level of biofilm production was found with both MDRO and not-MDRO with no significant differences between groups. All the methicillin-resistant Staphylococcus aureus (MRSA) and 80% of Pseudomonas aeruginosa MDR strains were found as moderate/high biofilm producers. Conversely, less than 17% of Klebsiella pneumoniae extended-spectrum beta-lactamase (ESBL), Escherichia coli-ESBL and Acinetobacter baumannii were moderate/high biofilm producers. Notably, those strains classified as non-biofilm producers, were always associated with biofilm producer bacteria in polymicrobial colonization. This study shows that biofilm producers were present in all chronic skin ulcers, suggesting that biofilm represents a key virulence determinant in promoting bacterial persistence and chronicity of ulcerative lesions independently from the MDRO phenotype.

The expression ratios of estrogen receptor α (ERα) to estrogen receptor ß1 (ERß1) and ERα to ERß2 identify poor clinical outcome in endometrioid endometrial cancer.

The prognostic relevance of estrogen (ER) and progesterone receptor (PR) expression in endometrioid endometrial cancer is still controversially discussed. The present study has focused on the evaluation of the prognostic value of ERα, ERß1, ERß2, and PR in this histotype. Specifically, we were interested in evaluating whether the relative level of ER subtype-specific expression (in terms of a ratio ERα/ERß1 and ERα/ERß2) would predict clinical outcome better than their absolute levels in patients with endometrioid endometrial cancer. To this end, protein content was assessed by immunohistochemistry in a group of 121 cases and staining was analyzed in relation to clinicopathologic variables, disease-free survival and overall survival. Results obtained have demonstrated that none of the biological markers analyzed possess an independent prognostic role with regard to disease-free survival. Multivariate analysis of overall survival has shown that ERα alone is not an independent prognostic indicator in patients with endometrioid endometrial cancer (hazard ratio [HR]; 0.5; 95% confidence interval [CI], 0.09-3.0; P = .5). On the other hand, an ERα/ERß1 ratio of 1 or less or an ERα/ERß2 ratio of 1 or less has proved to be independently associated with a higher risk of death (HR, 6.4 [95% CI, 1.0-40.6; P = .04] and 9.7 [95% CI, 1.1-85.3; P = .04], respectively) along with age, tumor stage, and Ki-67. In conclusion, we report here that the ERα/ERß1 and ERα/ERß2 expression ratios are independent prognostic markers of survival in endometrioid endometrial cancer; these findings suggest that phenotyping these interacting markers conjointly may better predict patient survival than each individual marker alone.

Modelling co-infection of the cystic fibrosis lung by Pseudomonas aeruginosa and Burkholderia cenocepacia reveals influences on biofilm formation and host response.

The Gram-negative bacteria Pseudomonas aeruginosa and Burkholderia cenocepacia are opportunistic human pathogens that are responsible for severe nosocomial infections in immunocompromised patients and those suffering from cystic fibrosis (CF). These two bacteria have been shown to form biofilms in the airways of CF patients that make such infections more difficult to treat. Only recently have scientists begun to appreciate the complicated interplay between microorganisms during polymicrobial infection of the CF airway and the implications they may have for disease prognosis and response to therapy.To gain insight into the possible role that interaction between strains of P. aeruginosa and B. cenocepacia may play during infection, we characterised co-inoculations of in vivo and in vitro infection models. Co-inoculations were examined in an in vitro biofilm model and in a murine model of chronic infection. Assessment of biofilm formation showed that B. cenocepacia positively influenced P. aeruginosa biofilm development by increasing biomass. Interestingly, co-infection experiments in the mouse model revealed that P. aeruginosa did not change its ability to establish chronic infection in the presence of B. cenocepacia but co-infection did appear to increase host inflammatory response.Taken together, these results indicate that the co-infection of P. aeruginosa and B. cenocepacia leads to increased biofilm formation and increased host inflammatory response in the mouse model of chronic infection. These observations suggest that alteration of bacterial behavior due to interspecies interactions may be important for disease progression and persistent infection.