ABSTRACT
Polymyxin-carbapenem-resistant Klebsiella pneumoniae (PCR-Kp) with pan (PDR)- or extensively drug-resistant phenotypes has been increasingly described worldwide. Here, we report a PCR-Kp outbreak causing untreatable infections descriptively correlated with bacterial genomes. Hospital-wide surveillance of PCR-Kp was initiated in December-2014, after the first detection of a K. pneumoniae phenotype initially classified as PDR, recovered from close spatiotemporal cases of a sentinel hospital in Rio de Janeiro. Whole-genome sequencing of clinical PCR-Kp was performed to investigate similarities and dissimilarities in phylogeny, resistance and virulence genes, plasmid structures and genetic polymorphisms. A target phenotypic profile was detected in 10% (12/117) of the tested K. pneumoniae complex bacteria recovered from patients (8.5%, 8/94) who had epidemiological links and were involved in intractable infections and death, with combined therapeutic drugs failing to meet synergy. Two resistant bacterial clades belong to the same transmission cluster (ST437) or might have different sources (ST11). The severity of infection was likely related to patients' comorbidities, lack of antimicrobial therapy and predicted bacterial genes related to high resistance, survival, and proliferation. This report contributes to the actual knowledge about the natural history of PCR-Kp infection, while reporting from a time when there were no licensed drugs in the world to treat some of these infections. More studies comparing clinical findings with bacterial genetic markers during clonal spread are needed.
Subject(s)
Klebsiella Infections , Polymyxins , Humans , Polymyxins/pharmacology , Polymyxins/therapeutic use , Klebsiella pneumoniae , Klebsiella Infections/drug therapy , Klebsiella Infections/epidemiology , Klebsiella Infections/genetics , Brazil , Genome, Bacterial , Disease Outbreaks , Carbapenems/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests , beta-Lactamases/genetics , Bacterial Proteins/geneticsABSTRACT
The transforming growth factor-betas (TGF-betas) comprise a family of pleiotropic members that signal through two types of serine/threonine kinase receptors, named TGFRI (TGF-beta type I receptor) and TGFRII (TGF-beta type II receptor). We previously demonstrated that cortical neurons increase the astrocyte maturation marker, glial fibrillary acidic protein (GFAP), and thus, astrocyte differentiation, by inducing TGF-beta1 secretion by astrocytes in vitro. Although TGF-beta receptor expression has been described in different brain regions and cell types, their localization is still a subject of discussion. In the present work, we analyzed TGFRII expression in cultured cortical astrocytes from embryonic and newborn animals by immunocytochemistry, Western blot, and reverse transcriptase-polymerase chain reaction (RT-PCR). We report for the first time expression of TGFRII in embryonic glia. TGFRII immunostaining was punctual and spread throughout the cellular membrane of embryonic and newborn astrocytes. Western blot and RT-PCR assays revealed similar levels of the receptor in astrocytes from different ages. Identification of TGFRII in embryonic astrocytes is novel and might point to the multipotent precursor cell, radial glia, as a potential target for TGFbeta1 during astrocyte development.
