This work provides first evidence that the GAD system might play an essential role in the resistance of an environment-borne, pathogenic Brucella species to extreme acid shock and during passage through the host stomach following oral infection.

f Brucella is an expanding genus of major zoonotic pathogens, including at least 10 genetically very close species occupying a wide range of niches from soil to wildlife, livestock, and humans. Recently, we have shown that in the new species Brucella microti, the glutamate decarboxylase (Gad)-dependent system (GAD system) contributes to survival at a pH of 2.5 and also to infection in mice by the oral route. In order to study the functionality of the GAD system in the genus Brucella, 47 isolates, representative of all known species and strains of this genus, and 16 strains of the closest neighbor genus, Ochrobactrum, were studied using microbiological, biochemical, and genetic approaches. In agreement with the genome sequences, the GAD system of classical species was not functional, unlike that of most strains of Brucella ceti, Brucella pinnipedialis, and newly described species (B. microti, Brucella inopinata BO1, B. inopinata-like BO2, and Brucella sp. isolated from bullfrogs). In the presence of glutamate, these species were more acid resistant in vitro than classical terrestrial brucellae. Expression in trans of the gad locus from representative Brucella species in the Escherichia coli MG1655 mutant strain lacking the GAD system restored the acid-resistant phenotype. The highly conserved GAD system of the newly described or atypical Brucella species may play an important role in their adaptation to acidic external and host environments. Furthermore, the GAD phenotype was shown to be a useful diagnostic tool to distinguish these latter Brucella strains from Ochrobactrum and from classical terrestrial pathogenic Brucella species, which are GAD negative. Brucellae are the etiologic agents of brucellosis, the most widespread bacterial zoonosis, infecting livestock and humans (human incidence, 500,000/year). The disease is endemic in the Mediterranean, in Near East and Middle East countries, and in Latin America (1, 2). These pathogens are classified as different species on the basis of specific phenotypic traits and their natural hosts (3): Brucella melitensis (isolated from goats and sheep), Brucella abortus (cattle and bison), Brucella suis (pigs and wild boar), and Brucella canis (dogs). Transmitted to humans via the mucosal, cutaneous, respiratory or, most frequently, oral route, these species may induce undulant fever (Malta fever) and a wide range of clinical manifestations, including encephalitis and endocarditis. With a few exceptions, Brucella species isolated from marine mammals (Brucella pinnipedialis and Brucella ceti) have not been described as human pathogens. Two other species are nonpathogenic for humans: Brucella ovis (sheep) and Brucella neotomae (desert woodrat) (3). Being known for 20 years or longer, these eight species are considered "classical". More recently, three "new" species/strains were identified: B. microti from common vole, red fox, and also soil (4-7) and Brucella inopinata BO1 and B. inopinata-like BO2 from patients with a breast implant infection (8, 9) and a chronic destructiv...

Indirect evidence suggests that adipose tissue-derived stromal cells (ASCs) possess different physiological and biological variations related to the anatomical localization of the adipose depots. Accordingly, to investigate the influence of the tissue origin on the intrinsic properties of ASCs and to assess their response to specific stimuli, we compared the biological, functional and ultrastructural properties of two ASC pools derived from mediastinal and subcutaneous depots (thoracic compartment) by means of supplements such as platelet lysate (PL) and FBS. Subcutaneous ASCs exhibited higher proliferative and clonogenic abilities than mediastinal counterpart, as well as increased secreted levels of IL-6 combined with lower amount of VEGF-C. In contrast, mediastinal ASCs displayed enhanced pro-angiogenic and adipogenic differentiation properties, increased cell diameter and early autophagic processes, highlighted by electron microscopy. Our results further support the hypothesis that the origin of adipose tissue significantly defines the biological properties of ASCs, and that a homogeneric function for all ASCs cannot be assumed.

The consumption of extra virgin olive oil (EVOO), a common dietary habit of the Mediterranean people, seems to be related to a lower incidence of certain types of cancer including bladder neoplasm. Metastases are the major cause of bladder cancer-related deaths and targeting cell motility has been proposed as a therapeutic strategy to prevent cancer spread. This study aimed to investigate the potential antimetastatic effect of total phenols extracted from EVOO against the human transitional bladder carcinoma cell line T24. We also aimed at verifying that EVOO extract exerts cytotoxic effect on tumor cells without affecting normal urothelial fibroblasts. Our results show that EVOO extract can significantly inhibit the proliferation and motility of T24 bladder cells in a dose-dependent manner. In the same experimental conditions fibroblast proliferation and motility were not significantly modified. Furthermore the enzymatic activity of MMP-2 was inhibited at nontoxic EVOO extract doses only in T24 cells. The qRT-PCR revealed a decrease of the MMP-2 expression and a simultaneous increase of the tissue inhibitors of metalloproteinases expression. Our results may support the epidemiological evidences that link olive oil consumption to health benefits and may represent a starting point for the development of new anticancer strategies.