| 1. |
- Meng, Qinglai, et al.
(författare)
-
Rapid personalized AMR diagnostics using two-dimensional antibiotic resistance profiling strategy employing a thermometric NDM-1 biosensor
- 2021
-
Ingår i: Biosensors and Bioelectronics. - : Elsevier BV. - 0956-5663. ; 193
-
Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) threatens global public health and modern surgical medicine. Expression of β-lactamase genes is the major mechanism by which pathogens become antibiotic resistant. Pathogens expressing extended spectrum β-lactamases (ESBL) and carbapenemases (CP) are especially difficult to treat and are associated with increased hospitalization and mortality rates. Despite considerable effort, identification of ESBLs and CPs in a clinically relevant timeframe remains challenging. In this study, a two-dimensional AMR profiling assay strategy was developed employing panels of antibiotics (penicillins, cephamycins, oximino-cephalosporins and carbapenems) and β-lactamases inhibitors (avibactam and EDTA). The assay required the development of a novel biosensor that employed New Delhi metallo-β-lactamase-1 (NDM-1) as the sensing element. Functionally probing β-lactamase activity using substrates and inhibitors combinatorically increased the informational content that enabled the development of assays capable of simultaneous, differential identification of multiple β-lactamases expressed in a single bacterial isolate. More specifically, the assay enabled the simultaneous identification of ESBL and CP in mock samples, as well as in an engineered construct which co-expressed these β-lactamases. The NDM-1 biosensor assay was 16 times and 8 times more sensitive than the ESBL Nordmann/Dortet/Poirel (NDP) and Carba Nordmann/Poirel (NP) assays, respectively. In a retrospective study, NDM-1 biosensor assays were able to differentially identify ESBLs, metallo-CPs and serine-CPs β-lactamases in 23 clinical isolates with 100% accuracy. An assay algorithm was developed which accelerated data analytics reducing turnaround to <1 h. The assay strategy integrated with AI-based data analytics has the potential to provide physicians with a comprehensive readout of patient AMR status.
|
|
| 2. |
- Heyman, Jakob, et al.
(författare)
-
Landscape evolution of the northeastern Tibetan plateau - relict surfaces and fluvial margins
- 2007
-
Ingår i: Geophysical Research Abstracts.
-
Konferensbidrag (refereegranskat)abstract
- The actively uplifting Tibetan plateau has a profound impact on climate and displays a landscape marked by geomorphological action. This is because the uplift is counteracted by intense fluvial incision of some of the world’s largest rivers and their tributaries that drain the plateau. Glaciers and glacial landforms occur predominantly in and around the highest elevation areas. By investigating the imprints of glacial and fluvial erosion we can enhance our understanding of the long-term landscape evolution, as well as illuminate the paleoglaciology of the Tibetan plateau. We here present an investigation of the large-scale geomorphology of the northeastern Tibetan plateau and its implication for landscape evolution and paleoenvironmental reconstructions.The northeastern part of the Tibetan plateau is characterized by a plateau surface at c. 4300 m asl with higher mountain groups reaching up to 1500 m above the surrounding plateau surface. We used SRTM 90 m digital elevation model, satellite images and Google Earth imagery to map the large-scale geomorphology for an area of c. 135.000 km2 centered around the Bayan Har mountains. Our mapping reveals a clear pattern of substantial glacial erosion on the highest, central parts of the mountain areas and decreasing amounts of glacial erosion with decreasing elevation and increasing distance away from these centers of glaciation. Beyond the areas of glacial erosion, there is a low-relief fluvial landscape that typifies the rest of the plateau surface. The plateau margins are formed by steep fluvial valleys which cut backwards into the gentle sloping relict plateau surface. Thus, the overall landscape may be divided into three classes; (i) glacially eroded surfaces in the highest areas, (ii) a relict, low-relief plateau surface, and (iii) a steep, fluvial landscape juxtaposing the former two classes.The distribution of the different landscapes indicates the following temporal evolution of the landscape. The glacial landforms indicate a repeated glaciation of the mountain areas. The steep fluvial valleys consuming the relict plateau surface represent an ongoing adjustment of the river channels to the actively uplifting plateau margin. The pattern of abandoned fluvial erosion of the northern part of the study area supports the notion of a stepwise uplift. This is because progressively younger uplift of the northern parts of the area induced a piracy of originally N-flowing rivers to currently ESE-flowing rivers along major faults (such as we infer for the Huang He river). It is noteworthy that the outline of the relict landscape, that is the pronounced break in slope between the low-relief relict landscape and the young fluvial landscape, coincides almost completely with the outline of a hypothesized former ice sheet, the Huang He ice sheet. We have not been able to confirm the presence of geomorphology or stratigraphy that would support this reconstruction. If true, however, our notion of outline conformance could indicate that the Huang He ice sheet may actually have been larger than suggested and that glacial traces are being consumed by the fluvial incision triggered by plateau uplift.
|
|
| 3. |
- Meng, Qinglai, et al.
(författare)
-
Rapid Detection of Multiple Classes of β-Lactam Antibiotics in Blood Using an NDM-1 Biosensing Assay
- 2021
-
Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 10:9
-
Tidskriftsartikel (refereegranskat)abstract
- Currently, assays for rapid therapeutic drug monitoring (TDM) of β-lactam antibiotics in blood, which might be of benefit in optimizing doses for treatment of critically ill patients, remain challenging. Previously, we developed an assay for determining the penicillin-class antibiotics in blood using a thermometric penicillinase biosensor. The assay eliminates sample pretreatment, which makes it possible to perform semicontinuous penicillin determinations in blood. However, penicillinase has a narrow substrate specificity, which makes it unsuitable for detecting other classes of β-lactam antibiotics, such as cephalosporins and carbapenems. In order to assay these classes of clinically useful antibiotics, a novel biosensor was developed using New Delhi metallo-β-lactamase-1 (NDM-1) as the biological recognition layer. NDM-1 has a broad specificity range and is capable of hydrolyzing all classes of β-lactam antibiotics in high efficacy with the exception of monobactams. In this study, we demonstrated that the NDM-1 biosensor was able to quantify multiple classes of β-lactam antibiotics in blood plasma at concentrations ranging from 6.25 mg/L or 12.5 mg/L to 200 mg/L, which covered the therapeutic concentration windows of the tested antibiotics used to treat critically ill patients. The detection of ceftazidime and meropenem was not affected by the presence of the β-lactamase inhibitors avibactam and vaborbactam, respectively. Furthermore, both free and protein-bound β-lactams present in the antibiotic-spiked plasma samples were detected by the NDM-1 biosensor. These results indicated that the NDM-1 biosensor is a promising technique for rapid TDM of total β-lactam antibiotics present in the blood of critically ill patients.
|
|
