Antimicrobial resistance in wildlife and in the built environment in a wildlife rehabilitation center.

Injured and orphaned wildlife are often brought to Wildlife Rehabilitation Centers (WRC) to be cared for by professionals to ultimately be released back to their natural habitats. In these centers, animals may spend months and frequently receive prolonged antibiotic therapy. Therefore, WRC may play a role in the emergence and dissemination of antimicrobial resistance (AMR). The goal of this study was to investigate the presence and antibiotic resistance profiles of Gram-negative bacteria with reduced susceptibility to cephalosporins in both the wildlife admitted to a WRC and in the WRC built environment in Chile. A cross-sectional study was conducted sampling animals undergoing rehabilitation (n = 64) and the WRC environment (n = 160). Isolated bacterial species were identified with MALDI-TOF, and antimicrobial susceptibility determined using the disk diffusion method. Enterobacteriaceae and Pseudomonadaceae were the dominant bacterial families among the environmental (n = 78) and animal (n = 31) isolates. For Enterobacteriaceae, isolates of the most abundant species (E. coli) were classified into 20 antibiotic resistance profiles, with eight of those isolates being resistant to more than nine antibiotics, including imipenem. Isolates of the Pseudomonadaceae family identified 11 isolates with resistance to antibiotics such as carbapenems and quinolones. Even though a cluster analysis based on antibiotic resistance patterns did not show a clear overlap between environmental and animal isolates, it is important to highlight the identification of isolates resistant to carbapenems, which is very relevant from a public health perspective. Further, numerous antibiotic resistance profiles were observed in different bacterial species, indicating not only environmental contamination with a wide diversity of bacteria, but also a wide diversity of resistant bacteria in animals at the WRC. The approach taken by sampling animals and their hospital environment can be useful in understanding AMR dynamics in wildlife rehabilitation settings, as well as the potential dissemination of AMR into the natural environment.

Correction to: Ceramide and palmitic acid inhibit macrophage-mediated epithelial-mesenchymal transition in colorectal cancer.

The third and fifth author's affiliation was published incorrectly in the original article. Also, the Figure 5 and the Acknowledgement section was published incorrectly. The corrected affiliation, Figure 5 and the Acknowledgement section are provided in this correction.

Ceramide and palmitic acid inhibit macrophage-mediated epithelial-mesenchymal transition in colorectal cancer.

Accumulating evidence indicates that ceramide (Cer) and palmitic acid (PA) possess the ability to modulate switching of macrophage phenotypes and possess anti-tumorigenic effects; however, the underlying molecular mechanisms are largely unknown. The aim of the present study was to investigate whether Cer and PA could induce switching of macrophage polarization from the tumorigenic M2- towards the pro-inflammatory M1-phenotype, and whether this consequently altered the potential of colorectal cancer cells to undergo epithelial-mesenchymal transition (EMT), a hallmark of tumor progression. Our study showed that Cer- and PA-treated macrophages increased expression of the macrophage 1 (M1)-marker CD68 and secretion of IL-12 and attenuated expression of the macrophage 2 (M2)-marker CD163 and IL-10 secretion. Moreover, Cer and PA abolished M2 macrophage-induced EMT and migration of colorectal cancer cells. At the molecular level, this coincided with inhibition of SNAI1 and vimentin expression and upregulation of E-cadherin. Furthermore, Cer and PA attenuated expression levels of IL-10 in colorectal cancer cells co-cultured with M2 macrophages and downregulated STAT3 and NF-κB expression. For the first time, our findings suggest the presence of an IL-10-STAT3-NF-κB signaling axis in colorectal cancer cells co-cultured with M2 macrophages, mimicking the tumor microenvironment. Importantly, PA and Cer were powerful inhibitors of this signaling axis and, consequently, EMT of colorectal cancer cells. These results contribute to our understanding of the immunological mechanisms that underlie the anti-tumorigenic effects of lipids for future combination with drugs in the therapy of colorectal carcinoma.

Helicobacter pylori Induced Phosphatidylinositol-3-OH Kinase/mTOR Activation Increases Hypoxia Inducible Factor-1α to Promote Loss of Cyclin D1 and G0/G1 Cell Cycle Arrest in Human Gastric Cells.

Helicobacter pylori (H. pylori) is a human gastric pathogen that has been linked to the development of several gastric pathologies, such as gastritis, peptic ulcer, and gastric cancer. In the gastric epithelium, the bacterium modifies many signaling pathways, resulting in contradictory responses that favor both proliferation and apoptosis. Consistent with such observations, H. pylori activates routes associated with cell cycle progression and cell cycle arrest. H. pylori infection also induces the hypoxia-induced factor HIF-1α, a transcription factor known to promote expression of genes that permit metabolic adaptation to the hypoxic environment in tumors and angiogenesis. Recently, however, also roles for HIF-1α in the repair of damaged DNA and inhibition of gene expression were described. Here, we investigated signaling pathways induced by H. pylori in gastric cells that favor HIF-1α expression and the consequences thereof in infected cells. Our results revealed that H. pylori promoted PI3K/mTOR-dependent HIF-1α induction, HIF-1α translocation to the nucleus, and activity as a transcription factor as evidenced using a reporter assay. Surprisingly, however, transcription of known HIF-1α effector genes evaluated by qPCR analysis, revealed either no change (LDHA and GAPDH), statistically insignificant increases SLC2A1 (GLUT-1) or greatly enhance transcription (VEGFA), but in an HIF-1α-independent manner, as quantified by PCR analysis in cells with shRNA-mediated silencing of HIF-1α. Instead, HIF-1α knockdown facilitated G1/S progression and increased Cyclin D1 protein half-life, via a post-translational pathway. Taken together, these findings link H. pylori-induced PI3K-mTOR activation to HIF-1α induced G0/G1 cell cycle arrest by a Cyclin D1-dependent mechanism. Thus, HIF-1α is identified here as a mediator between survival and cell cycle arrest signaling activated by H. pylori infection.