The Enterobacter cloacae complex is an emerging opportunistic pathogen whose increased resistance to carbapenems is considered a public health problem. This is due to the loss of efficacy of beta-lactam antibiotics, which are used as the first treatment option in the management of infections caused by Gram-negative bacteria. The objective of this study was to perform the molecular characterization of 28 isolates of the E. cloacae complex resistant to cephalosporins and carbapenems isolated between 2011 and 2018 from five hospitals located in the municipality of Santiago de Cali, Colombia. Molecular detection of blaKPC, blaVIM, blaNDM and blaOXA-48-like genes was performed on these isolates and the genetic relationship between the isolates was assessed using multilocus sequence typing (MLST). Forty-three percent of the isolates carried the blaKPC-2 gene variant. MLST showed high genetic diversity among isolates, the most frequent being the sequence type ST510 with a frequency of 50%. The identification of the genes involved in carbapenem resistance and dispersing genotypes is an important step toward the development of effective prevention and epidemiological surveillance strategies in Colombian hospitals.
Background:The toll-like receptors (TLRs) are the most important pattern recognition receptors that sense invading pathogens and mount innate and adaptive immune response. TLRs are also suggested to contribute to the inflammatory process after allogeneic stem cell transplantation (allo-SCT). Unc-93 homolog B1 (UNC93B1) is a key regulator of TLRs and delivers them from the endoplasmic reticulum to their respective endosomal signaling compartments. UNC93B is encoded by the UNC93B1 gene on chromosome 11q13 and has one important single-nucleotide polymorphism (SNP) rs308328 (T>C) in an intronic region that is functional, and the major allele (T) has been reported to be associated with lower UNC93B1 expression. We therefore hypothesized that the UNC93B1 rs308328 might be associated with clinical outcomes after allo-SCT. Aims: We investigated the influence of the UNC93B1 SNP on transplant outcomes in a cohort of patients undergoing unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program (JMDP). Methods: The UNC93B1 genotyping was performed on 237 transplant recipients, including 109 with acute myeloid leukemia (AML; 46%), 57 with acute lymphoblastic leukemia (ALL; 24%), 37 with myelodysplastic syndrome (MDS; 16%), 10 with chronic myeloid leukemia (CML; 4%), and 24 with malignant lymphoma (ML; 10%), and their unrelated donors who underwent BMT through the JMDP with T cell-replete marrow from HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 allele-matched donors between January 2006 and December 2009. We retrospectively examined the impact of the UNC93B1 SNP on transplant outcomes. Results: The genotype frequencies of C/C, C/T, and T/T in the UNC93B1 SNP were 14%, 40% and 46% in the donors and 14%, 40% and 46% in the recipients (P = 0.98), respectively. The donor UNC93B1 C/C genotype was associated with a better 3-year overall survival (OS) than the donor UNC93B1 C/T or T/T genotype (77% vs. 58%; P = 0.040; Fig. 1). The donor UNC93B1 C/C genotype also exhibited a trend toward a lower 3-year transplant-related mortality (14% vs. 27%, P = 0.073) but did not reduce the 3-year relapse rate (13% vs. 17%, P = 0.72). The donor UNC93B1 C/C genotype remained associated with a better 3-year OS (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.18-0.97; P = 0.043) than the donor UNC93B1 C/T or T/T genotype in the multivariate analysis. Summary/Conclusion:The current study showed that the donor UN-C93B1 rs308328 C/C genotype, which putatively has higher inducibility of UNC93B1 than the UNC93B1 rs308328 C/T or T/T genotype, was associated with a better OS in patients with hematologic malignancies receiving unrelated BMT than the donor UNC93B1 rs308328 C/T or T/T genotype. An analysis of the UNC93B1 genotype could therefore be useful for selecting the donor, estimating the prognosis, and creating therapeutic strategies after allo-SCT, such as alterations in the in vivo regulation of the UNC93B1 gene.
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