FdeC expression regulates motility and adhesion of the avian pathogenic Escherichia coli strain IMT5155.

Adaptation of avian pathogenic E. coli (APEC) to changing host environments including virulence factors expression is vital for disease progression. FdeC is an autotransporter adhesin that plays a role in uropathogenic Escherichia coli (UPEC) adhesion to epithelial cells. Expression of fdeC is known to be regulated by environmental conditions in UPEC and Shiga toxin-producing E. coli (STEC). The observation in a previous study that an APEC strain IMT5155 in which the fdeC gene was disrupted by a transposon insertion resulted in elevated adhesion to chicken intestinal cells prompted us to further explore the role of fdeC in infection. We found that the fdeC gene prevalence and FdeC variant prevalence differed between APEC and nonpathogenic E. coli genomes. Expression of the fdeC gene was induced at host body temperature, an infection relevant condition. Disruption of fdeC resulted in greater adhesion to CHIC-8E11 cells and increased motility at 42 °C compared to wild type (WT) and higher expression of multiple transporter proteins that increased inorganic ion export. Increased motility may be related to increased inorganic ion export since this resulted in downregulation of YbjN, a protein known to supress motility. Inactivation of fdeC in APEC strain IMT5155 resulted in a weaker immune response in chickens compared to WT in experimental infections. Our findings suggest that FdeC is upregulated in the host and contributes to interactions with the host by down-modulating motility during colonization. A thorough understanding of the regulation and function of FdeC could provide novel insights into E. coli pathogenesis.

Shotgun proteomics of archival triple-negative breast cancer samples.

PURPOSE: Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers, and has a worse prognosis compared with hormone receptor-positive disease. Its unfavorable outcome and the lack of hormonal receptors determine the use of adjuvant chemotherapy as part of the standard treatment for these tumors, although several studies have documented that the current standard combination chemotherapy is suboptimal. Therefore, a new functional taxonomy of breast cancer and new targets for therapeutic development are urgently needed. EXPERIMENTAL DESIGN: In this study, we have analyzed the proteome of TNBC applying a high-throughput proteomics approach to routinely archived formalin-fixed, paraffin-embedded tumor tissues. RESULTS: We have been able to identify and quantify more than 1000 protein groups. Some of these proteins are of outstanding interest in the biology and clinical management of this disease, such as CD44 and PARP1. Moreover, we have characterized some signaling pathways that could be related to TNBC genesis and development. CONCLUSION AND CLINICAL RELEVANCE: Our results open up new avenues for the use of proteomics technologies in clinically relevant studies using archival samples. Shotgun LC-MS/MS studies could serve to discover new biomarkers and may provide clues to the genesis of TNBC and underlying molecular alterations.