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Microorganisms that inhabit unchartered unique soil such as in the highly saline and hot Red Sea lagoons on the Saudi Arabian coastline, represent untapped sources of potentially new bioactive compounds. In this study, a culture-dependent approach was applied to three types of sediments: mangrove mud (MN), microbial mat (MM), and barren soil (BS), collected from Rabigh harbor lagoon (RHL) and Al-Kharrar lagoon (AKL). The isolated bacteria were evaluated for their potential to produce bioactive compounds. The phylogenetic characterization of 251 bacterial isolates based on the 16S rRNA gene sequencing, supported their assignment to five different phyla: Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Planctomycetes. Fifteen putative novel species were identified based on a 16S rRNA gene sequence similarity to other strain sequences in the NCBI database, being ≥98%. We demonstrate that 49 of the 251 isolates exhibit the potential to produce antimicrobial compounds. Additionally, at least one type of biosynthetic gene sequence, responsible for the synthesis of secondary metabolites, was recovered from 25 of the 49 isolates. Moreover, 10 of the isolates had a growth inhibition effect towards Staphylococcus aureus, Salmonella typhimurium and Pseudomonas syringae. We report the previously unknown antimicrobial activity of B. borstelensis, P. dendritiformis and M. salipaludis against all three indicator pathogens. Our study demonstrates the evidence of diverse cultured microbes associated with the Red Sea harbor/lagoon environments and their potential to produce antimicrobial compounds. [ABSTRACT FROM AUTHOR]

Wnt ligand-driven tumor growth is inhibited by the soluble Wnt inhibitor Fzd8CRD, but the mechanism through which this effect is mediated is unknown. In the MMTV-Wnt1 mouse model, regression of mammary tumors by Fzd8CRD treatment coincides with an acute and strong induction of insulin-like growth factor (IGF)- binding protein IGFBP5, an antagonist of IGF signaling that mediates involution of mammary gland in females after offspring are weaned. In this study, we show that repression of this IGF inhibitory pathway is crucial for Wntdriven growth of mammary tumors. We found that IGFBP5 regulation was mediated by the β-catenin-dependent Wnt pathway. Wnt, in addition to IGF ligands, facilitated tumor growth by paracrine communication among tumor cells. In addition, Fzd8CRD caused precocious induction of IGFBP5 in normal mammary glands undergoing involution, implying an acceleration of the involution process by inhibition of Wnt signaling. The molecular and phenotypic parallel between tumor regression and mammary gland involution suggests that Wntdriven mammary tumors use the same growth mechanism as proliferating normal mammary glands. [ABSTRACT FROM AUTHOR]

Background: Histological examinations of MMTV-Wnt1 tumors reveal drastic differences in the tumor vasculature whenqcompared to MMTV-Her2 tumors. However, these differences have not been formally described, nor have any angiogenicqfactors been implicated to be involved in the Wnt1 tumors. Methodology/Principal Findings: Here, we show that MMTV-Wnt1 tumors were more vascularized than MMTV-Her2qtumors, and this correlated with significantly higher expression of a CXC chemokine, stromal cell-derived factor-1 (SDF1/qCXCL12) but not with VEGFA. Isolation of various cell types from Wnt1 tumors revealed that SDF1 was produced by bothqtumor myoepithelial cells and stromal cells, whereas Her2 tumors lacked myoepithelial cells and contained significantly lessqstroma. The growth of Wnt1 tumors, but not Her2 tumors, was inhibited by a neutralizing antibody to SDF1, but not byqneutralization of VEGFA. Anti-SDF1 treatment decreased the proportion of infiltrating Gr1+ myeloid cells in the Wnt1 tumors,qwhich correlated with a decrease in the percentage of endothelial cells. The involvement of Gr1+ cells was evident from theqretardation of Wnt1 tumor growth following in vivo depletion of these cells with an anti-Gr1-specific antibody. This degreeqof inhibition on Wnt1 tumor growth was comparable, but not additive, to the effect observed with anti-SDF1, indicative ofqoverlapping mechanisms of inhibition. In contrast, Her2 tumors were not affected by the depletion of Gr1+ cells. Conclusions/Significance: We demonstrated that SDF1 is important for Wnt1, but not for HER2, in inducing murineqmammary tumor and the role of SDF1 in tumorigenesis involves Gr1+ myeloid cells to facilitate growth and/or angiogenesis. [ABSTRACT FROM AUTHOR]