Article type : Review ArticleA current review of pathogenicity determinants of Streptococcus spp.

Streptococcus agalactiae is among the most relevant aetiologic agent of bovine clinical and subclinical mastitis, a major problem for the dairy industry. The disease may cause significant economic loss due to decreased production and milk quality and increased use of medicaments. Presently, data demonstrated that biofilm formation favours the establishment of infectious process in health mammary tissue by S. agalactiae and emphasizes that an acidic pH promotes adhesion by biofilm-forming bacterial strains. S. agalactiae strains (25%) showed resistance to tetracycline, azithromycin, erythromycin and clindamycin, and consequently were classified as multidrug-resistant strains.

Sepsis is a generalized disease characterized by an extreme response to a severe infection. Moreover, challenges remain in the diagnosis, treatment and management of septic patients. In this mini-review we demonstrate developments on cellular pathogenesis and the role of Caveolin-1 (Cav-1) in sepsis. Studies have shown that Cav-1 has a significant role in sepsis through the regulation of membrane traffic and intracellular signaling pathways. In addition, activation of apoptosis/autophagy is considered relevant for the progression and development of sepsis. However, how Cav-1 is involved in sepsis remains unclear, and the precise mechanisms need to be further investigated. Finally, the role of Cav-1 in altering cell permeability during inflammation, in sepsis caused by microorganisms, apoptosis/autophagy activation and new therapies under study are discussed in this mini-review.

BACKGROUND Streptococcus agalactiae capsular type III strains are a leading cause of invasive neonatal infections. Many pathogens have developed mechanisms to escape from host defense response using the host membrane microdomain machinery. Lipid rafts play an important role in a variety of cellular functions and the benefit provided by interaction with lipid rafts can vary from one pathogen to another. OBJECTIVES This study aims to evaluate the involvement of membrane microdomains during infection of human endothelial cell by S. agalactiae. METHODS The effects of cholesterol depletion and PI3K/AKT signaling pathway activation during S. agalactiae-human umbilical vein endothelial cells (HUVEC) interaction were analysed by pre-treatment with methyl-β-cyclodextrin (MβCD) or LY294002 inhibitors, immunofluorescence and immunoblot analysis. The involvement of lipid rafts was analysed by colocalisation of bacteria with flotillin-1 and caveolin-1 using fluorescence confocal microscopy. FINDINGSIn this work, we demonstrated the importance of the integrity of lipid rafts microdomains and activation of PI3K/Akt pathway during invasion of S. agalactiae strain to HUVEC cells. Our results suggest the involvement of flotillin-1 and caveolin-1 during the invasion of S. agalactiae strain in HUVEC cells.CONCLUSIONS The collection of our results suggests that lipid microdomain affects the interaction of S. agalactiae type III belonging to the hypervirulent ST-17 with HUVEC cells through PI3K/Akt signaling pathway.Key words: S. agalactiae -lipid rafts -flotillin-1 -caveolin-1 -HUVEC -PI3K/Akt pathway Streptococcus agalactiae is a leading cause of neonatal infections, such as meningitis, sepsis and pneumonia. (1) In particular, S. agalactiae capsular type III strains belonging to the hypervirulent clonal complex 17 have been significantly associated with meningitis and account for up to 44 early onset disease and 67% late onset disease cases compared with less than 10% of colonising isolates. (2,3) Microorganisms interact with host cell lipid rafts microdomains to enter and survive inside the cell. (4) Lipid rafts play an important role in a variety of cellular functions, including polarisation, signal transduction, endocytosis, secretion, cell-cell and cell-pathogen adhesion. Several pathogens, such as viruses, bacteria and protozoa, can use the host-cell lipid rafts to secure their entrance and maintenance inside target cells. The benefit provided by interaction with lipid rafts can vary from one pathogen to another. (5) Lipid rafts are considered as dynamic assemblies of cholesterol and sphingolipids in

No abstract