iThe spread of the plasmid-mediated colistin resistance gene, mcr-1, into carbapenem-resistant Enterobacteriaceae (CRE) clinical isolates poses a significant threat to global health. Here we report the identification of three mcr-1-harboring carbapenem-resistant Escherichia coli strains, collected from three patients in two provinces in China. Our results show that mcr-1-harboring CRE strains have started to spread in different hospitals in China. In addition, this report presents the first description of chromosomal integration of mcr-1 into a carbapenem-resistant E. coli strain. Polymyxins B and E (also known as colistin) are among some antibiotics of the last resort used to treat serious infections caused by carbapenem-resistant Enterobacteriaceae (CRE). However, the recent discovery of a plasmid-mediated colistin resistance gene, mcr-1, sounded the alarm that last-resort antibiotics may be in jeopardy (1). Of particular concern is the spread of mcr-1 into CRE, creating extensively drug-resistant isolates causing untreatable disease. We have recently reported the cooccurrence of NDM-5 carbapenemase and MCR-1 within the same clinical isolate from a tertiary hospital in eastern China (2). The isolates coproducing MCR-1 and NDM-5 were nonsusceptible to nearly all antimicrobial agents tested (2). It is worrisome that these MCR-1-producing CRE isolates may spread further into hospital settings and within high-risk patients, thereby causing untreatable infections. Here we conducted a molecular screening study for clinical CRE isolates collected from six tertiary hospitals in six provinces in order to explore the dissemination of MCR-1-producing CRE in China.A total of 264 clinical CRE isolates were collected from six large regional hospitals in northern (Beijing), eastern (Suzhou), southern (Guangzhou), northwestern (Yinchuan), and southwestern (Chengdu and Kunming) China between January 2014 and December 2015. They were isolated from respiratory tract (n ϭ 119), urine (n ϭ 50), blood (n ϭ 38), intra-abdominal (n ϭ 22), skin and soft tissue (n ϭ 17), rectal swab (n ϭ 9), wound (n ϭ 5), and other sites (n ϭ 4) of 251 unique patients and included 160 Klebsiella pneumoniae, 36 Escherichia coli, 19 Enterobacter cloacae, 17 E. aerogenes, 11 K. oxytoca, 5 Citrobacter freundii, 4 Serratia, 3 Morganella morganii, 3 Providencia rettgeri, and 3 K. ozaenae spp. and 3 other species. Species identification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (Bruker Microflex LT). PCR detection of carbapenemase genes (bla KPC , bla NDM , bla VIM , bla OXA48-like , and bla IMP ) showed that 134 isolates were positive for bla KPC , 69 for bla NDM , 18 for bla IMP , and 7 for bla VIM , while 59 were negative for any carbapenemase gene. Thirty-one isolates were found to carry more than one carbapenemase. We then tested for the presence of mcr-1 using a previously published PCR method (1) and identified a total of five mcr-1-harboring CRE isolates from four different patients in three diff...

Lactoferrin is an antimicrobial protein present in human mucosal secretions as well as saliva. As there is no information on the relative fungicidal activity of human and bovine lactoferrin, an oral isolate of Candida albicans was studied for its susceptibility to these two proteins. Exposure to a concentration of 20 micrograms ml-1 of either HLF or BLF at 37 degrees C inactivated the yeast to the same degree irrespective of the incubation time of 45, 90 or 150 min. A similar study, using 20 micrograms ml-1 BLF and an incubation time of 150 min, elicited varying anticandidal activity against 35 isolates belonging to six different Candida species. Thus, BLF was fungicidal for the six Candida species in the following decreasing order, C. tropicalis > C. krusei > C. albicans > C. guilliermondii > C. parapsilosis > C. glabrata; the latter being the most resistant. These Candida species also demonstrated significant intra-species variation in susceptibility to the protein (P < 0.05). When the yeast cells exposed to BLF were examined by cryo-scanning electron microscopy, profound cell wall changes such as cell surface blebs, swelling and cell collapse were noted. These findings suggest that lactoferrin, a constituent of saliva, may differentially modulate the carriage of Candida species in the oral cavity.

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Abstract miR-143-3p is correlated with inflammatory pain responses, such as hsa-miR-143-3p expression reduction in fibromyalgia. The present study aimed to explore the effects of miR-143-3p and Toll-like receptor (TLR) 4/myeloid differentiation factor 88 (MyD88)/NF-κB signaling pathway on pulmonary inflammatory factors levels and alveolar epithelial cell apoptosis in mycoplasmal pneumonia mice. Twenty mice were selected as normal group. The 120 successfully modeled Mycoplasma pneumoniae (MP) infection mice were randomly divided into model group (without any treatment), negative control (NC) group (injected with NC mimic), miR-143-3p mimic group (injected with miR-143-3p mimic), miR-143-3p inhibitor group (injected with miR-143-3p inhibitor), TAK-242 group (treatment with TAK-242), and miR-143-3p inhibitor + TAK-242 group (treatment with miR-143-3p inhibitor + TAK-242). Compared with model group, model mice had up-regulated miR-143-3p expression and decreased MyD88 and p-NF-κB p50 protein expressions (all P&lt;0.05); Model mice treated with miR-143-3p mimic and TAK-242 had reduced interleukin (IL)-2 and tumor necrosis factor (TNF)-α contents and protein expressions of MyD88, p-NF-κB p50, increased IL-10 content, fewer alveolar epithelial cell apoptosis, lower Bax expression and higher Bcl-2 expression (all P&lt;0.05); however, mice with miR-143-3p inhibitor treatment showed opposite trends in terms of above indicators. The exacerbation of mycoplasmal pneumonia caused by miR-143-3p inhibitor was partly improved by miR-143-3p inhibitor + TAK-242 combination treatment (all P&lt;0.05). Therefore, up-regulation of miR-143-3p expression may ameliorate pulmonary inflammatory factors levels and reduce alveolar epithelial cell apoptosis in mycoplasmal pneumonia mice by inhibiting TLR4/MyD88/NF-κB signaling pathway.

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