Genomic Profile of a Multidrug-Resistant Klebsiella pneumoniae Strain Isolated from a Urine Specimen.

Klebsiella pneumoniae is an opportunistic pathogen mostly found in health care-associated infections but can also be associated with community-acquired infections and is in critical need of new antimicrobial agents for strains resistant to carbapenems. The prevalence of carbapenemase-encoding genes varies among studies. Multidrug-resistant K. pneumoniae strains can harbor several antimicrobial-resistant determinants and mobile genetic elements (MGEs), along with virulence genetic determinants in community settings. We aim to determine the genetic profile of a multidrug-resistant K. pneumoniae strain isolated from a patient with community-acquired UTI. We isolated a K. pneumoniae strain UABC-Str0120, from a urine sample of community-acquired urinary tract infection. Antimicrobial susceptibility tests and Whole-genome sequencing (WGS) were performed. The phylogenetic relationship was inferred by SNPs calling and filtering. UABC-Str0120 showed resistance toward ß-lactams, combinations with ß-lactamase inhibitors, and carbapenems. WGS revealed the presence of genes conferring resistance to aminoglycosides, ß-lactams, carbapenems, quinolones, sulfonamides, phosphonates, phenicols, and quaternary ammonium compounds, 77 subsystems of virulence genes were identified, and an uncommon sequence type ST5889 was also determined. The sequenced strain harbors several MGEs. The UABC-Str0120 recovered from a urine sample harbors several virulence and antimicrobial resistance determinants, which assembles an endangering combination for an immunocompromised or a seemly healthy host, given its presence in a community setting.

Impact of cholesterol-pathways on breast cancer development, a metabolic landscape.

ApoB-lipoproteins and their components modulate intracellular metabolism and have been associated with the development of neoplastic phenomena, such as proliferation, anchorage-independent growth, epithelial-mesenchymal transition, and cancer invasion. In cancer cells, the modulation of targets that regulate cholesterol metabolism, such as synthesis de novo, endocytosis, and oxidation, are contributing factors to cancer development. While mechanisms associated with sterol regulatory element-binding protein 2 (SREBP-2)/mevalonate, the low-density lipoprotein receptor (LDL-R) and liver X receptor (LXR) have been linked with tumor growth; metabolites derived from cholesterol-oxidation, such as oxysterols and epoxy-cholesterols, also have been described as tumor processes-inducers. From this notion, we perform an analysis of the role of lipoproteins, their association with intracellular cholesterol metabolism, and the impact of these conditions on breast cancer development, mechanisms that can be shared during atherogenesis promoted mainly by LDL. Pathways connecting plasma dyslipidemias in conjunction with the effect of cholesterol-derived metabolites on intracellular mechanisms and cellular plasticity phenomena could provide new approaches to elucidate the triggering factors of carcinogenesis, conditions that could be considered in the development of new therapeutic approaches.

Protein complexes associated with ß-catenin differentially influence the differentiation profile of neonatal and adult CD8+ T cells.

The canonical Wnt signaling pathway is a master cell regulator involved in CD8+ T cell proliferation and differentiation. In human CD8+ T cells, this pathway induces differentiation into memory cells or a "stem cell memory like" population, which is preferentially present in cord blood. To better understand the role of canonical Wnt signals in neonatal or adult blood, we compared the proteins associated with ß-catenin, in nonstimulated and Wnt3a-stimulated human neonatal and adult naive CD8+ T cells. Differentially recruited proteins established different complexes in adult and neonatal cells. In the former, ß-catenin-associated proteins were linked to cell signaling and immunological functions, whereas those of neonates were linked to proliferation and metabolism. Wnt3a stimulation led to the recruitment and overexpression of Wnt11 in adult cells and Wnt5a in neonatal cells, suggesting a differential connexion with planar polarity and Wnt/Ca2+ noncanonical pathways, respectively. The chromatin immunoprecipitation polymerase chain reaction ß-catenin was recruited to a higher level on the promoters of cell renewal genes in neonatal cells and of differentiation genes in those of adults. We found a preferential association of ß-catenin with CBP in neonatal cells and with p300 in the adult samples, which could be involved in a higher self-renewal capacity of the neonatal cells and memory commitment in those of adults. Altogether, our results show that different proteins associated with ß-catenin during Wnt3a activation mediate a differential response of neonatal and adult human CD8+ T cells.