CTX-M group gene distribution of extended spectrum beta-lactamase-producing Enterobacteriaceae at a Japanese Children's hospital.

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have spread globally as one of the most common multidrug resistant organisms. Although a wide variety of ESBL genes were known in each geographical region, few reports existed on the distribution of ESBL genes in Japanese children. To clarify the distribution of ESBL genes, we investigated the CTX-M type of the ESBL-producing Enterobacteriaceae and patient characteristics among hospital-acquired and community-acquired cases. Total of 253 isolates of ESBL-producing Enterobacteriaceae were recovered from 238 pediatric patients. ESBL-producing Enterobacteriaceae were mostly recovered from children with underlying diseases (76.5%). Ratio of community-acquired and hospital-acquired cases was 58.8% and 41.2%, respectively. Compared to the hospital-acquired cases, community-acquired cases had younger age, fewer underlying diseases, and the dominant detection of Escherichia coli. The most common ESBL-producing Enterobacteriaceae was E. coli (79.8%), followed by Klebsiella pneumoniae (9.1%). CTX-M9 group was the most prevalent CTX-M group gene (63.2%), which was dominantly detected in E. coli (72.7%). This was the largest descriptive study to find CTX-M9 group as the most prevalent ESBL genotype among Enterobacteriaceae isolated from Japanese children in line with adult's epidemiology.

Epithelial-mesenchymal transition of A549 cells is enhanced by co-cultured with THP-1 macrophages under hypoxic conditions.

Epithelial-mesenchymal transition (EMT) is associated with pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF). In this study, we investigated EMT of human pulmonary epithelial-derived cells (A549). A549 cells was either cultured by itself or co-cultured with THP-1 macrophages under normoxic (21% O2) and hypoxic (2% O2) conditions. We evaluated the presence of EMT by determining the expression of EMT markers, E-cadherin, vimentin, and fibronectin. To determine the role of TGF-ß1 and IL-1ß in EMT of the A549 cells, we analyzed the effects of blocking their activity with TGF-ß1 inhibitor or IL-1ß neutralizing antibody respectively. The A549 cells presented EMT when they were co-cultured with THP-1 macrophages. The EMT of the A549 cells co-cultured with THP-1 macrophages was exacerbated under hypoxia. In addition, the EMT were prevented by the addition of TGF-ß1 type I receptor kinase inhibitor. The hypoxic condition increased the mRNA levels of TGF-ß1 in A549 cells and THP-1 macrophages and that of IL-1ß in THP-1 macrophages when each cells were co-cultured. Anti-IL-1ß neutralizing antibody attenuated TGF-ß1 secretion in co-culture media under hypoxic conditions. Thus, the IL-1ß from THP-1 macrophages up-regulated the TGF-ß1 from A549 cells and THP-1 macrophages, and then the TGF-ß1 from both cells induced and promoted the EMT of A549 cells when they were co-cultured under hypoxia. Together, these results demonstrate that the interaction between type II pneumocytes and macrophages under hypoxia is necessary for the development of pulmonary fibrosis.