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Formic acid (FA) has been used for decades to control Varroa destructor , one of the most important parasites of the western honey bee, Apis mellifera . The rather unselective molecular mode of action of FA and its possible effects on honeybees have long been a concern of beekeepers, as it has undesirable side effects that affect the health of bee colonies. This study focuses on short-term transcriptomic changes as analysed by RNAseq in both larval and adult honey bees and in mites after FA treatment under applied conditions. Our study aims to identify those genes in honey bees and varroa mites differentially expressed upon a typical FA hive exposure scenario. Five detoxification-related genes were identified with significantly enhanced and one gene with significantly decreased expression under FA exposure. Regulated genes in our test setting included members of various cytochrome P450 subfamilies, a flavin-dependent monooxygenase and a cytosolic 10-formyltetrahydrofolate dehydrogenase (FDH), known to be involved in formate metabolism in mammals. We were able to detect differences in the regulation of detoxification-associated genes between mites and honey bees as well as between the two different developmental stages of the honey bee. Additionally, we detected repressed regulation of Varroa genes involved in cellular respiration, suggesting mitochondrial dysfunction and supporting the current view on the mode of action of FA—inhibition of oxidative phosphorylation. This study shows distinct cellular effects induced by FA on the global transcriptome of both host and parasite in comparison. Our expression data might help to identify possible differences in the affected metabolic pathways and thus make a first contribution to elucidate the mode of detoxification of FA.

The ectoparasite Varroa destructor Anderson and Trueman is the most important parasites of the western honey bee, Apis mellifera L . The most widely currently used treatment uses formic acid (FA), but the understanding of its effects on V . destructor is limited. In order to understand the mechanism of action of FA, its effect on Varroa mites was investigated using proteomic analysis by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). V . destructor was collected from honey bee colonies with natural mite infestation before and 24 h after the initiation of FA treatment and subjected to proteome analysis. A total of 2637 proteins were identified. Quantitative analysis of differentially expressed candidate proteins (fold change ≥ 1.5; p ≤ 0.05) revealed 205 differentially expressed proteins: 91 were induced and 114 repressed in the FA-treated group compared to the untreated control group. Impaired protein synthesis accompanied by increased protein and amino acid degradation suggest an imbalance in proteostasis. Signs of oxidative stress included significant dysregulation of candidate proteins of mitochondrial cellular respiration, increased endocytosis, and induction of heat shock proteins. Furthermore, an increased concentration of several candidate proteins associated with detoxification was observed. These results suggest dysregulated cellular respiration triggered by FA treatment as well as an increase in cellular defense mechanisms, including induced heat shock proteins and detoxification enzymes.

Introduction The global increase of multidrug-resistant organisms (MDROs) is one of the most urgent public health threats affecting both humans and animals. The One Health concept emphasizes the interconnectedness of human, animal and environmental health and highlights the need for integrated approaches to combat antimicrobial resistance (AMR). Although the sharing of environments and antimicrobial agents between companion animals and humans poses a risk for MDRO transmission, companion animals have been studied to a lesser extent than livestock animals. This study therefore used core genome multilocus sequence typing (cgMLST) to investigate the genetic relationships and putative transmission of MDROs between humans and pets. Methods This descriptive integrated typing study included 252 human isolates, 53 dog isolates and 10 cat isolates collected from 2019 to 2022 at the Charité University Hospital in Berlin, Germany. CgMLST was performed to characterize methicillin-resistant Staphylococcus aureus , vancomycin-resistant enterococci and multidrug-resistant gram-negative bacteria. The genetic diversity of the MDROs of the different host populations was determined and compared based on sequence type and core genome complex type. Results Within this study the majority of samples from pets and humans was genetically distinct. However, for some isolates, the number of allelic differences identified by cgMLST was low. Two cases of putative household transmission or shared source of VR E. faecium and MDR E. coli between humans and pets were documented. Conclusions The interaction between humans and their pets appears to play a minor role in the spread of the MDROs studied. However, further research is needed. This study emphasizes the importance of comprehensive molecular surveillance and a multidisciplinary One Health approach to understand and contain the spread of MDROs in human and animal populations. Trial Registration The study is registered with the German Clinical Trials Register (DRKS00030009).

The ectoparasite Varroa destructor Anderson and Trueman is the most important parasites of the western honey bee, Apis mellifera L. The most widely currently used treatment uses formic acid (FA), but the understanding of its effects on V. destructor is limited. In order to understand the mechanism of action of FA, its effect on Varroa mites was investigated using proteomic analysis by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). V. destructor was collected from honey bee colonies with natural mite infestation before and 24 h after the initiation of FA treatment and subjected to proteome analysis. A total of 2637 proteins were identified. Quantitative analysis of differentially expressed candidate proteins (fold change ≥ 1.5; p ≤ 0.05) revealed 205 differentially expressed proteins: 91 were induced and 114 repressed in the FA-treated group compared to the untreated control group. Impaired protein synthesis accompanied by increased protein and amino acid degradation suggest an imbalance in proteostasis. Signs of oxidative stress included significant dysregulation of candidate proteins of mitochondrial cellular respiration, increased endocytosis, and induction of heat shock proteins. Furthermore, an increased concentration of several candidate proteins associated with detoxification was observed. These results suggest dysregulated cellular respiration triggered by FA treatment as well as an increase in cellular defense mechanisms, including induced heat shock proteins and detoxification enzymes.