Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers

BACKGROUND: Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel\u27s effects on the gut resistome remain largely unknown. METHODS: Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of 190 Dutch individuals, before and after travel to diverse international locations. RESULTS: Travel markedly increased the abundance and α-diversity of AMR genes in the travelers\u27 gut resistome, and we determined that 56 unique AMR genes showed significant acquisition following international travel. These acquisition events were biased towards AMR genes with efflux, inactivation, and target replacement resistance mechanisms. Travel-induced shaping of the gut resistome had distinct correlations with geographical destination, so individuals returning to The Netherlands from the same destination country were more likely to have similar resistome features. Finally, we identified and detailed specific acquisition events of high-risk, mobile genetic element-associated AMR genes including qnr fluoroquinolone resistance genes, bla CONCLUSIONS: Our results show that travel shapes the architecture of the human gut resistome and results in AMR gene acquisition against a variety of antimicrobial drug classes. These broad acquisitions highlight the putative risks that international travel poses to public health by gut resistome perturbation and the global spread of locally endemic AMR genes

Impact of international travel and diarrhea on gut microbiome and resistome dynamics

International travel contributes to the global spread of antimicrobial resistance. Travelers\u27 diarrhea exacerbates the risk of acquiring multidrug-resistant organisms and can lead to persistent gastrointestinal disturbance post-travel. However, little is known about the impact of diarrhea on travelers\u27 gut microbiomes, and the dynamics of these changes throughout travel. Here, we assembled a cohort of 159 international students visiting the Andean city of Cusco, Peru and applied next-generation sequencing techniques to 718 longitudinally-collected stool samples. We find that gut microbiome composition changed significantly throughout travel, but taxonomic diversity remained stable. However, diarrhea disrupted this stability and resulted in an increased abundance of antimicrobial resistance genes that can remain high for weeks. We also identified taxa differentially abundant between diarrheal and non-diarrheal samples, which were used to develop a classification model that distinguishes between these disease states. Additionally, we sequenced the genomes of 212 diarrheagenic Escherichia coli isolates and found those from travelers who experienced diarrhea encoded more antimicrobial resistance genes than those who did not. In this work, we find the gut microbiomes of international travelers\u27 are resilient to dysbiosis; however, they are also susceptible to colonization by multidrug-resistant bacteria, a risk that is more pronounced in travelers with diarrhea

Manure microbial communities and resistance profiles reconfigure after transition to manure pits and differ from those in fertilized field soil

In agricultural settings, microbes and antimicrobial resistance genes (ARGs) have the potential to be transferred across diverse environments and ecosystems. The consequences of these microbial transfers are unclear and understudied. On dairy farms, the storage of cow manure in manure pits and subsequent application to field soil as a fertilizer may facilitate the spread of the mammalian gut microbiome and its associated ARGs to the environment. To determine the extent of both taxonomic and resistance similarity during these transitions, we collected fresh manure, manure from pits, and field soil across 15 different dairy farms for three consecutive seasons. We used a combination of shotgun metagenomic sequencing and functional metagenomics to quantitatively interrogate taxonomic and ARG compositional variation on farms. We found that as the microbiome transitions from fresh dairy cow manure to manure pits, microbial taxonomic compositions and resistance profiles experience distinct restructuring, including decreases in alpha diversity and shifts in specific ARG abundances that potentially correspond to fresh manure going from a gut-structured community to an environment-structured community. Further, we did not find evidence of shared microbial community or a transfer of ARGs between manure and field soil microbiomes. Our results suggest that fresh manure experiences a compositional change in manure pits during storage and that the storage of manure in manure pits does not result in a depletion of ARGs. We did not find evidence of taxonomic or ARG restructuring of soil microbiota with the application of manure to field soils, as soil communities remained resilient to manure-induced perturbation

Low Power, Wide Range Synthesizer for 534 MHz–18.56 GHz Band with FoM of − 192.45 dBc/Hz

A wide range frequency synthesizer is designed with the help of dual voltage tunable Differential Ring Oscillator (DRO). Frequency ranging from 534[Formula: see text]MHz to 18.56[Formula: see text]GHz can be generated using the proposed synthesizer. As proposed circuit utilizes dual voltage tunable DRO, a select input is provided to control the output frequency range. Logic low value (0[Formula: see text]V) of select input generates frequencies from 534[Formula: see text]MHz to 5.08[Formula: see text]GHz whereas logic high value (1.1[Formula: see text]V) of select input enables the frequency generation in the range of 5.08[Formula: see text]GHz to 18.56[Formula: see text]GHz. This work utilizes a single charge pump and single loop filter along with charge pump and bias control circuit. Proposed circuit is designed in GPDK 45-nm CMOS technology with supply voltage of 1.1[Formula: see text]V. Power consumption of the proposed circuits is 2.88[Formula: see text]mW while generating frequency of 7.84[Formula: see text]GHz. Proposed synthesizer demonstrates Figure of Merit (FoM2) of [Formula: see text][Formula: see text]dBc/Hz at this frequency. Because of such a wide spectrum, this synthesizer is well suited in the field of satellite communication, GPS and navigation. </jats:p