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Küeltz, D.

Publications and source records attributed to Küeltz, D..

2 recordsLinked to original sources

Identification of key proteins involved in stickleback environmental adaption with system-level analysis

Using abundance measurements of 1,490 proteins from four separate populations of three-spined sticklebacks, we implemented a system-level approach to correlate proteome dynamics with environmental salinity and temperature and the fishs population and morphotype. We identified sets of robust and accurate fingerprints that predict environmental salinity, temperature, morphotype and the population sample origin, observing that proteins with specific functions are enriched in these fingerprints. Highly apparent functions represented in all fingerprints include ion transport, proteostasis, growth, and immunity, suggesting that these functions are most diversified in populations inhabiting different environments. Applying a differential network approach, we analyzed the network of protein interactions that differs between populations. Looking at specific population combinations of differential interaction, we identify sets of connected proteins. We find that these sets and their corresponding enriched functions reflect key processes that have diverged between the four populations. Moreover, the extent of divergence, i.e. the number of enriched functions that differ between populations, is highest when all three environmental parameters are different between two populations. Key nodes in the differential interaction network signify functions that are also inherent in the fingerprints, most prominently proteostasis-related functions. However, the differential interaction network also reveals additional functions that have diverged between populations, notably cytoskeletal organization and morphogenesis. Having such a large proteomic dataset, the strength of these analyses is that the results are purely data-driven, not based on previous findings and hypotheses about adaptation. With such an unbiased approach applied on a large proteomic dataset, we find the strongest signals given by the data, making it possible to develop more discriminatory and complex biomarkers for specific contexts of interest.

systems biology↗

Diverse Mechanisms of Resistance in Carbapenem-Resistant Enterobacteriaceae at a Health Care System in Silicon Valley, California

Carbapenem-resistant Enterobacteriaceae (CRE) are emerging as a major health threat in North America. The mechanism of resistance to carbapenems has therapeutic and public health implications. We comprehensively characterized the underlying mechanisms of carbapenem resistance in CRE isolates recovered between 2013 and 2016 at a health system in Northern California. Genotypic methods were used to detect carbapenemases and plasmid-encoded cephalosporinases, and mass spectrometry was used to quantify relative porin levels for OmpC and OmpF and their analogs. MICs for imipenem-relebactam, meropenem-vaborbactam, ceftazidime-avibactam, and ceftolozane-tazobactam were measured. Whole genome sequencing was used for strain typing. A carbapenemase gene encoding blaOXA-48 like, blaNDM, blaKPC, blaSME, blaIMP, and blaVIM was detected in 38.7% (24/62) of CRE isolates. Porin levels was down at least 2-fold in 91.9% (57/62) of isolates. Including carbapenemase genes and porin loss, the mechanism of resistance was identified in 95.2% (59/62) of CRE isolates. Of the carbapenemase gene-positive isolates, blaKPC -positive isolates were 100% susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam; blaOXA-48 like-positive isolates were 100% susceptible to ceftazidime-avibactam; and blaSME-positive isolates were 100% susceptible to meropenem-vaborbactam and ceftolozane-tazobactam. 100% (38/38), 92.1% (35/38), 89.5% (34/38), and 31.6% (12/38) of carbapenemase gene-negative CRE isolates were susceptible to ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and ceftolozane-tazobactam, respectively. None of the CRE strains were genetically identical. In conclusion, at this health system in Silicon Valley, carbapenemase-producing CRE occurred sporadically and were mediated by diverse mechanisms. Nucleic acid testing for blaOXA-48 like, blaNDM, blaKPC, blaIMP, and blaVIM was sufficient to distinguish between carbapenemase-producing and non-producing CRE and accurately predicted susceptibility to ceftazidime-avibactam, meropenem-vaborbactam and imipenem-relebactam.

microbiology↗