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Lee, T. H.

Publications and source records attributed to Lee, T. H..

2 recordsLinked to original sources

Dominance of ST131 Escherichia coli carrying blaCTX-M in patients with bloodstream infections caused by cephalosporin-resistant strains in Australia, New Zealand and Singapore: whole genome analysis of isolates from a randomised trial

Synopsis/AbstractO_ST_ABSObjectivesC_ST_ABSTo characterise multi-drug resistant Escherichia coli isolated from patients in Australia, New Zealand and Singapore with bloodstream infection (BSI).\n\nMethodsWe prospectively collected third-generation cephalosporin resistant (3GC-R) E. coli from blood cultures obtained from patients enrolled in a randomised controlled trial. Whole genome sequencing was used to characterise antibiotic resistance genes, sequence types (STs), plasmids and phylogenetic relationships. Antibiotic susceptibility was determined using disk diffusion and Etest.\n\nResultsA total of 70 E. coli were included, of which the majority were ST131 (61.4%). BSI was most frequently from a urinary source (69.6%), community-associated (62.9%) and in older patients (median age 71 years [IQR 64-81]). The median Pitt bacteraemia score at presentation was 1 (IQR 0-2, range 0-3) and ICU admission was infrequent (3.1%). ST131 possessed significantly more acquired resistance genes than non-ST131 (p=0.003). Clade C1/C2 ST131 predominated (30.2% and 53.5% of all ST131 respectively) and these were all resistant to ciprofloxacin. All clade A ST131 were community-associated. The predominant ESBL types were blaCTX-M (78.6% of isolates) and were strongly associated with ST131, with the majority blaCTX-M-15. Clade C1 was associated with blaCTX-M-14 and blaCTX-M-27, whereas blaCTX-M-15 predominated in clade C2. Plasmid-mediated AmpC (p-AmpC) genes (mainly blaCMY-2) were also frequent (17.1%) but were more common with non-ST131 strains (p< 0.001). The majority of plasmid replicon types were IncF.\n\nConclusionsIn a prospective collection of 3GC-R E. coli causing BSI in the Australasian region, community-associated Clade C1/C2 ST131 predominate in association with blaCTX-M ESBLs, although a significant proportion of non-ST131 strains carried blaCMY-2.

microbiology

PRDX6 inhibits neurogenesis of neural precursor cells through downregulation of wdfy1 mediated TLR4 signal

Impaired neurogenesis has been associated with brain disorders. The role of peroxiredoxin 6 (PRDX6) in the neurodegenerative diseases is very controversial. To demonstrate the role of PRDX6 in neurogenesis, we compared neurogenesis ability and studied the molecular mechanisms. It was found that the neurogenesis of neural stem cells and expression of the marker protein were lowered in PRDX6 Tg-mice compared with non-tg mice. Moreover, the expression of wdfy1 was dramatically decreased in PRDX6-Tg mice, also, we observed that wdfy1 siRNA decreases the differentiation ability of primary neural stem cells to astrocyte and neuronal cells as well as PC12 cells. However, knockdown of PRDX6 recovered neurogenesis in the brain of PRDX6-Tg mice as well as PC-12 cells. We also showed that TLR4 was dramatically reduced in PRDX6 Tg mice as well as PC-12 cells and PRDX6 overexpression reduced neurogenesis was rescued after treatment of TLR4 siRNA. We further found that reduced TLR4 expression and neurogenesis was reversed in the neuron from PRDX6-Tg mice as well as PC12 cells by introduction of wdfy1 plasmid. Moreover, TLR4 siRNA reduced neurogenesis and wdfy1 expression. This study indicated that PRDX6 inhibits neurogenesis of neural precursor cells through TLR4 dependent downregulation of wdfy1.

developmental biology