DNA adducts are produced both exogenously and endogenously via exposure to various DNA-damaging agents. Two lipid peroxidation (LPO) products, 4-oxo-2(E)-nonenal (4-ONE) and 4-oxo-2(E)-hexenal (4-OHE), induce substituted etheno-DNA adducts in cells and chemically treated animals, but the adduct levels in humans have never been reported. It is important to investigate the occurrence of 4-ONE- and 4-OHE-derived DNA adducts in humans to further understand their potential impact on human health. In this study, we conducted DNA adductome analysis of several human specimens of pulmonary DNA as well as various LPO-induced DNA adducts in 68 human autopsy tissues, including colon, heart, kidney, liver, lung, pancreas, small intestine, and spleen, by liquid chromatography tandem mass spectrometry. In the adductome analysis, DNA adducts derived from 4-ONE and 4-OHE, namely, heptanone-etheno-2'-deoxycytidine (HεdC), heptanone-etheno-2'-deoxyadenosine (HεdA), and butanone-etheno-2'-deoxycytidine (BεdC), were identified as major adducts in one human pulmonary DNA. Quantitative analysis revealed 4-ONE-derived HεdC, HεdA, and heptanone-etheno-2'-deoxyguanosine (HεdG) to be ubiquitous in various human tissues at median values of 10, 15, and 8.6 adducts per 10(8) bases, respectively. More importantly, an extremely high level (more than 100 per 10(8) bases) of these DNA adducts was observed in several cases. The level of 4-OHE-derived BεdC was highly correlated with that of HεdC (R(2) = 0.94), although BεdC was present at about a 7-fold lower concentration than HεdC. These results suggest that 4-ONE- and 4-OHE-derived DNA adducts are likely to be significant DNA adducts in human tissues, with potential for deleterious effects on human health.
BackgroundAdvances in Aeromonas taxonomy have led to the reclassification of aeromonads. Hereon, we aimed to re-evaluate the characteristics of Aeromonas bacteremia, including those of a novel species, Aeromonas dhakensis.Methodology/Principal FindingsA retrospective study of monomicrobial Aeromonas bacteremia at a medical center in southern Taiwan from 2004–2011 was conducted. Species identification was based on rpoB sequencing. Of bacteremia of 153 eligible patients, A. veronii (50 isolates, 32.7%), A. dhakensis (48, 31.4%), A. caviae (43, 28.1%), and A. hydrophila (10, 6.5%) were the principal causative species. A. dhakensis and A. veronii bacteremia were mainly community-acquired and presented as primary bacteremia, spontaneous bacterial peritonitis, or skin and soft-tissue infection, whereas A. caviae was associated with hospital-onset bacteremia. The distribution of the AmpC β-lactamase and metallo-β-lactamase genes was species-specific: bla AQU-1, bla MOX, or bla CepH was present in A. dhakensis, A. caviae, or A. hydrophila, respectively, and bla CphA was present in A. veronii, A. dhakensis, and A. hydrophila. The cefotaxime resistance rates of the A. caviae, A. dhakensis, and A. hydrophila isolates were higher than that of A. veronii (39.5%%, 25.0%, and 30% vs. 2%, respectively). A. dhakensis bacteremia was linked to the highest 14-day sepsis-related mortality rate, followed by A. hydrophila, A. veronii, and A. caviae bacteremia (25.5%, 22.2%, 14.0%, and 4.7%, respectively; P = 0.048). Multivariate analysis revealed that A. dhakensis bacteremia, active malignancies, and a Pitt bacteremia score ≥ 4 was an independent mortality risk factor.Conclusions/SignificanceCharacteristics of Aeromonas bacteremia vary between species. A. dhakensis prevalence and its associated poor outcomes suggest it an important human pathogen.
Wastewater is considered a major source of antibiotic-resistant bacteria released into the environment. Here, we characterized carbapenemase-producing (CPE) in wastewater by whole-genome analysis. Wastewater samples ( = 40) were collected from municipal wastewater treatment plants and hospital wastewater in Japan and Taiwan. Samples were screened for CPE using selective media, and the obtained isolates were sequenced using an Illumina MiSeq. The isolates ( = 45) included the following microorganisms: ( = 12), ( = 10), complex ( = 10), ( = 8), ( = 2), ( = 1), ( = 1), and ( = 1). Among the 45 isolates, 38 harbored at least one carbapenemase-encoding gene. Of these, the (, , and) genes were found in 29 isolates. The genes were situated in novel class 1 integrons, but the integron structures were different between the Japanese (In1439 with and In1440 with) and Taiwanese (In1441 with and In1442 with) isolates. Other carbapenemase-encoding genes (, ,, , and) were found in one to three isolates. Notably, class 1 integrons previously reported among clinical isolates obtained in the same regions as the present study, namely, In477 with and In73 with, were found among the Japanese and Taiwanese isolates, respectively. The results indicate that CPE with various carbapenemase-encoding genes in different genetic contexts were present in biologically treated wastewater, highlighting the need to monitor for antibiotic resistance in wastewater.
SummaryCumulative evidence described the emergence and geographical expansion of azoleresistant A. fumigatus associated with azole treatment failure. To investigate the status of azole resistance in A. fumigatus in Taiwan, we studied 38 A. fumigatus clinical isolates cultivated from 31 patients at two teaching hospitals from 2011 to 2014. Three isolates obtained from respiratory samples of two azole-na€ ıve patients with pulmonary aspergillosis were found to display multi-azole resistance and cross resistance to agricultural azole fungicides, and all carried TR 34 /L98H mutations in cyp51A gene. The prevalence rates of azole resistance were 7.9% and 6.5% based on isolates and patients respectively. A phylogenetic analysis suggested genetic diversity of the TR 34 /L98H isolates in Taiwan, including a unique genotype distinct from strains outside Taiwan. The result underlines the emergence of such isolates in Taiwan as well, emphasising the importance of further surveillance for azoleresistant A. fumigatus and implementation of strategies that prevent fungicide-driven resistance selection.
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