RESUMO
Except the addition of TBL1Y in human, transducing beta like 1 (TBL1) family mainly consists of two members TBL1X and TBL1XR1, taking part in multiple intracellular signaling pathways such as Wnt/ß-catenin and NF-κB in cancer progression. However, the gene expression patterns of this family during embryonic development remain largely unknown. Here we took advantage of zebrafish model to characterize the spatial and temporal expression patterns of TBL1 family genes including tbl1x, tbl1xr1a and tbl1xr1b. The in situ hybridization studies of gene expression showed robust expressions of tbl1x and tbl1xr1b as maternal transcripts except tbl1xr1a. As the embryo develops, zygotic expressions of all TBL1 family members occur and have a redundant and broad pattern including in brain, neural retina, pharyngeal arches, otic vesicles, and pectoral fins. Ubiquitous expression of all family members were ranked from the strongest to the weakest: tbl1xr1a, tbl1x, and tbl1xr1b. In addition, one tbl1xr1a transcript tbl1xr1a202 showed unique and rich expression in the developing heart and lateral line neuromasts. Overall, all members of zebrafish TBL1 family shared numerous similarities and exhibited certain distinctions in the expression patterns, indicating that they might have redundant and exclusive functions to be further explored.
Assuntos
Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Transdução de Sinais , Transducina/genética , Transducina/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Klebsiella pneumoniae is an opportunistic pathogen commonly associated with nosocomial infections. In our previous study, we have demonstrated that colistin-resistant K. pneumoniae is more susceptible to killing by lytic tailed phages than the colistin-sensitive parent strain, including T1-like ФNJS1. This fitness cost associated with colistin resistance is due to the alteration of the surface charge that promotes phage adherence and infection. However, the receptor for phage adsorption has not been identified. In this study, we found that ФNJS1 specifically infected nonmucoid K. pneumoniae isolates, and the accelerated phage adsorption to colistin-resistant nonmucoid K. pneumoniae cells is reversible. Further research suggested that bacteria lipopolysaccharide may be involved in phage reversible adsorption, while capsule polysaccharide may block the receptors on cell surface from phage attachment. Transposon mutagenesis of colistin-resistant K. pneumoniae revealed that mutation in wecA and wecG, two genes involved in lipopolysaccharide O-antigen biosynthesis, significantly deceased phage adsorption capacity and infection efficiency. Inactivation of wzyE, which leaded to the shorten of O-antigen chain length, enhanced phage infectivity. Moreover, mutation of the outer membrane protein FepA slowed the phage lysis rate, suggesting that FepA may be an irreversible receptor for ФNJS1. In summary, our results show a delicate balance between ФNJS1 and its hosts, where the lipopolysaccharide O-antigen may serve as an essential reversible receptor for phage NJS1, while the long O-antigen chain hinders the bacteriophage infection.