Blood-generating heart-forming organoids recapitulate co-development of the human haematopoietic system and the embryonic heart.

Despite the biomedical importance of haematopoietic stem cells and haematopoietic progenitor cells, their in vitro stabilization in a developmental context has not been achieved due to limited knowledge of signals and markers specifying the multiple haematopoietic waves as well as ethically restricted access to the human embryo. Thus, an in vitro approach resembling aspects of haematopoietic development in the context of neighbouring tissues is of interest. Our established human pluripotent stem cell-derived heart-forming organoids (HFOs) recapitulate aspects of heart, vasculature and foregut co-development. Modulating HFO differentiation, we here report the generation of blood-generating HFOs. While maintaining a functional ventricular-like heart anlagen, blood-generating HFOs comprise a mesenchyme-embedded haemogenic endothelial layer encompassing multiple haematopoietic derivatives and haematopoietic progenitor cells with erythro-myeloid and lymphoid potential, reflecting aspects of primitive and definitive haematopoiesis. The model enables the morphologically structured co-development of cardiac, endothelial and multipotent haematopoietic tissues equivalent to the intra-embryonic haematopoietic region in vivo, promoting research on haematopoiesis in vitro.

Integrative multiomic approaches reveal ZMAT3 and p21 as conserved hubs in the p53 tumor suppression network.

TP53 , the most frequently mutated gene in human cancer, encodes a transcriptional activator that induces myriad downstream target genes. Despite the importance of p53 in tumor suppression, the specific p53 target genes important for tumor suppression remain unclear. Recent studies have identified the p53-inducible gene Zmat3 as a critical effector of tumor suppression, but many questions remain regarding its p53-dependence, activity across contexts, and mechanism of tumor suppression alone and in cooperation with other p53-inducible genes. To address these questions, we used Tuba-seq Ultra somatic genome editing and tumor barcoding in a mouse lung adenocarcinoma model, combinatorial in vivo CRISPR/Cas9 screens, meta-analyses of gene expression and Cancer Dependency Map data, and integrative RNA-sequencing and shotgun proteomic analyses. We established Zmat3 as a core component of p53-mediated tumor suppression and identified Cdkn1a as the most potent cooperating p53-induced gene in tumor suppression. We discovered that ZMAT3/CDKN1A serve as near-universal effectors of p53-mediated tumor suppression that regulate cell division, migration, and extracellular matrix organization. Accordingly, combined Zmat3 - Cdkn1a inactivation dramatically enhanced cell proliferation and migration compared to controls, akin to p53 inactivation. Together, our findings place ZMAT3 and CDKN1A as hubs of a p53-induced gene program that opposes tumorigenesis across various cellular and genetic contexts.

A multicenter study on accuracy and reproducibility of nanopore sequencing-based genotyping of bacterial pathogens.

Nanopore sequencing has shown the potential to democratize genomic pathogen surveillance due to its ease of use and low entry cost. However, recent genotyping studies showed discrepant results compared to gold-standard short-read sequencing. Furthermore, although essential for widespread application, the reproducibility of nanopore-only genotyping remains largely unresolved. In our multicenter performance study involving five laboratories, four public health-relevant bacterial species were sequenced with the latest R10.4.1 flow cells and V14 chemistry. Core genome MLST analysis of over 500 data sets revealed highly strain-specific typing errors in all species in each laboratory. Investigation of the methylation-related errors revealed consistent DNA motifs at error-prone sites across participants at read level. Depending on the frequency of incorrect target reads, this either leads to correct or incorrect typing, whereby only minimal frequency deviations can randomly determine the final result. PCR preamplification, recent basecalling model updates and an optimized polishing strategy notably diminished the non-reproducible typing. Our study highlights the potential for new errors to appear with each newly sequenced strain and lays the foundation for computational approaches to reduce such typing errors. In conclusion, our multicenter study shows the necessity for a new validation concept for nanopore sequencing-based, standardized bacterial typing, where single nucleotide accuracy is critical.

Influence of learning strategies and motivation on anatomy test performance of undergraduate medical students.

To learn and comprehend the large amount of information in gross anatomy, undergraduate students must self-regulate their learning to be properly prepared for the exams within the available time. Even though there are many studies on learning strategies and their influence on test results and motivation, the aim of this study is to investigate characteristics of learning strategies in detail and in relation to the anatomy course of first semester students and how their use is related to anatomy test performance. For assessing the learning strategies, we used the short version of the questionnaire "Learning Strategies of University Students" (LIST-K) (Klingsieck, 2018). Further, we investigated potential influences of motivation and resources used during the self-regulated learning process. The participants in this study (N = 108) filled in the above-mentioned questionnaire LIST-K and a written multiple-choice anatomy test. A k-means cluster analysis revealed three groups of students differing in their self-reported use of learning strategies. Students used either (1) predominantly metacognitive and resource-related strategies, (2) predominantly cognitive strategies, or (3) no specific learning strategies at all. We found no significant overall relationships between the use of learning strategies and test performance. A stepwise linear regression identified the use of cognitive learning strategies (ß =.269) as a significant predictor for test performance (R² =.149, p =.003), possibly as these specific learning strategies help with a systematic and effective approach while studying anatomy and retrieving large amount of memorized information. Further, motivation was identified as a negative predictor (ß = -.277), which might be a result of the short time periods students have to study for exams. Overall findings underline the importance of self-regulated learning as a positive predictor for academic performance. By understanding these factors, a more student-centered approach could be adopted by educators to improve medical education and equip students with valuable approaches for their continuous education, even beyond university.

The genetic architecture of repeated local adaptation to climate in distantly related plants.

Closely related species often use the same genes to adapt to similar environments. However, we know little about why such genes possess increased adaptive potential and whether this is conserved across deeper evolutionary lineages. Adaptation to climate presents a natural laboratory to test these ideas, as even distantly related species must contend with similar stresses. Here, we re-analyse genomic data from thousands of individuals from 25 plant species as diverged as lodgepole pine and Arabidopsis (~300 Myr). We test for genetic repeatability based on within-species associations between allele frequencies in genes and variation in 21 climate variables. Our results demonstrate significant statistical evidence for genetic repeatability across deep time that is not expected under randomness, identifying a suite of 108 gene families (orthogroups) and gene functions that repeatedly drive local adaptation to climate. This set includes many orthogroups with well-known functions in abiotic stress response. Using gene co-expression networks to quantify pleiotropy, we find that orthogroups with stronger evidence for repeatability exhibit greater network centrality and broader expression across tissues (higher pleiotropy), contrary to the 'cost of complexity' theory. These gene families may be important in helping wild and crop species cope with future climate change, representing important candidates for future study.

Tumor board simulation improves interdisciplinary decision-making in medical students.

INTRODUCTION: Training of interdisciplinary clinical reasoning and decision-making skills, essential in daily clinical practice in oncological specialties, are still underrepresented in medical education. Therefore, at LMU University Hospital Munich, we implemented a didactically modified tumor board simulation with experts from five different disciplines (medical oncology, pathology, radiation oncology, radiology, and surgery) presenting patient cases into a one-week course on the basic principles of oncology. In this survey, we examined the self-assessed impact of our course on the interdisciplinary decision-making skills of medical students. METHODS: Between November-December 2023 and January-February 2024, we surveyed two cohorts of medical students in the third year of medical school in our one-week course before and after participating in the tumor board simulation. The objective was to evaluate the self-assessed knowledge in interdisciplinary clinical decision-making, in integrating ethical considerations into clinical reasoning, and in comprehension of various professional viewpoints in interdisciplinary decision-making. Knowledge was assessed using a five-step Likert scale from 1 (no knowledge) to 5 (complete knowledge). RESULTS: The survey was answered by 76 students before and 55 after the simulation, equaling 60-70% of all 100 course participants. Mean knowledge level regarding principles of interdisciplinary clinical decision-making improved significantly in all of the following exemplary aspects: purpose and procedure of tumor boards in clinical practice (from 2.4 ± 1.1 to 4.0 ± 1.0, Spearman's ρ = 0.6, p < 0.001), principles of dealing with ethical challenges in oncology (from 2.4 ± 1.1 to 3.4 ± 1.0, ρ = 0.4, p < 0.001), and principles of shared decision-making in oncology (2.7 ± 1.1 to 3.7 ± 1.0, ρ = 0.4, p < 0.001). Students reported that their skills in clinical decision-making and ability to discuss oncological patient cases from different professional viewpoints improved due to the teaching course. CONCLUSION: By employing our interdisciplinary one-week course and a didactically modified tumor board simulation featuring experts from various oncological disciplines, medical students' comprehension of interdisciplinary clinical decision-making in oncology improved significantly.

Prevalence of Anxiety and Depression Symptoms among University Teachers in Ethiopia during the COVID-19 Pandemic.

A growing body of evidence suggests an increased prevalence of anxiety and depression among teachers during the COVID-19 pandemic. However, there is little evidence in research documenting the extent of anxiety and depression in the university teacher population and how these relate to feelings of loneliness. This study aims to explore the prevalence of anxiety and depression symptoms among university teachers, identify differences, and further examine the relationships between loneliness and symptoms of anxiety and depression. The study participants included university teachers in the College of Health and Medical Sciences from four purposefully selected public universities who completed a survey questionnaire consisting of items that measured anxiety and depressive symptoms as well as loneliness. The final sample included 148 participants (45 participants [30.4%] located in the center or capital; 125 (83.1%) men; and 90 [62.5%] taught both online and face-to-face). The university teachers' sample mean age = 39.07 had an SD = 7.67. As per the findings of this study, the prevalence of anxiety and depression symptoms was significant (11% and 12.3%) among university teachers in Ethiopia during the COVID-19 pandemic. Also, this study found a significant association between these symptoms and loneliness. Therefore, incorporating relevant strategies to promote mental well-being and targeting individuals who felt lonely were essential for overcoming health-related burdens. Universities should equip teachers with resources to prevent mental health issues and offer need-based counseling services to alleviate them.

Cost-effective, open-source light shutters with Arduino control.

In optical experiments, shutters are devices that open or close a path of light. They are often used to limit the duration of light exposure onto a target or onto a detector to reduce possible light-induced damage. Many commercial shutters are available for different applications - some provide very fast opening and closing times, some can handle large optical powers, and others allow for fail-safe operation. Many of these devices are costly and offer limited control options. Here we provide an open-source design for a low-cost, general purpose shutter system based on ubiquitous actuators (servo motors or solenoids) that are connected to an Arduino-based controller. Several shutters can be controlled by one controller, further reducing system cost. The state of the shutters can be controlled via a display built into the controller, by serial commands via USB, or by electrical control lines. The use of a microcontroller makes the shutter controller adaptable - only control options that are used need to be included, and the design accommodates a selection of display and actuator options. We provide designs for all required components, including 3D print files for the actuator holders and cases, the Arduino code, libraries for serial communication (C and python), and example graphical user interfaces for testing.

p53 target ANKRA2 cooperates with RFX7 to regulate tumor suppressor genes.

The transcription factor regulatory factor X 7 (RFX7) has been identified as a tumor suppressor that is recurrently mutated in lymphoid cancers and appears to be dysregulated in many other cancers. RFX7 is activated by the well-known tumor suppressor p53 and regulates several other known tumor suppressor genes. However, what other factors regulate RFX7 and its target genes remains unclear. Here, reporter gene assays were used to identify that RFX7 regulates the tumor suppressor gene PDCD4 through direct interaction with its X-box promoter motif. We utilized mass spectrometry to identify factors that bind to DNA together with RFX7. In addition to RFX7, we also identified RFX5, RFXAP, RFXANK, and ANKRA2 that bind to the X-box motif in the PDCD4 promoter. We demonstrate that ANKRA2 is a bona fide direct p53 target gene. We used transcriptome analyses in two cell systems to identify genes regulated by ANKRA2, its sibling RFXANK, and RFX7. These results revealed that ANKRA2 functions as a critical cofactor of RFX7, whereas RFXANK regulates largely distinct gene sets.

Radiographical diagnostic competences of dental students using various feedback methods and integrating an artificial intelligence application-A randomized clinical trial.

INTRODUCTION: Radiographic diagnostic competences are a primary focus of dental education. This study assessed two feedback methods to enhance learning outcomes and explored the feasibility of artificial intelligence (AI) to support education. MATERIALS AND METHODS: Fourth-year dental students had access to 16 virtual radiological example cases for 8 weeks. They were randomly assigned to either elaborated feedback (eF) or knowledge of results feedback (KOR) based on expert consensus. Students´ diagnostic competences were tested on bitewing/periapical radiographs for detection of caries, apical periodontitis, accuracy for all radiological findings and image quality. We additionally assessed the accuracy of an AI system (dentalXrai Pro 3.0), where applicable. Data were analysed descriptively and using ROC analysis (accuracy, sensitivity, specificity, AUC). Groups were compared with Welch's t-test. RESULTS: Among 55 students, the eF group by large performed significantly better than the KOR group in detecting enamel caries (accuracy 0.840 ± 0.041, p = .196; sensitivity 0.638 ± 0.204, p = .037; specificity 0.859 ± 0.050, p = .410; ROC AUC 0.748 ± 0.094, p = .020), apical periodontitis (accuracy 0.813 ± 0.095, p = .011; sensitivity 0.476 ± 0.230, p = .003; specificity 0.914 ± 0.108, p = .292; ROC AUC 0.695 ± 0.123, p = .001) and in assessing the image quality of periapical images (p = .031). No significant differences were observed for the other outcomes. The AI showed almost perfect diagnostic performance (enamel caries: accuracy 0.964, sensitivity 0.857, specificity 0.074; dentin caries: accuracy 0.988, sensitivity 0.941, specificity 1.0; overall: accuracy 0.976, sensitivity 0.958, specificity 0.983). CONCLUSION: Elaborated feedback can improve student's radiographic diagnostic competences, particularly in detecting enamel caries and apical periodontitis. Using an AI may constitute an alternative to expert labelling of radiographs.

Why did I participate in an HIV vaccine study? Experiences of participation in the first phase II HIV vaccine trial in Mozambique: An ancillary study using a mixed-method approach.

Introduction: This study recognized the lack of information regarding recruitment and retention factors associated with implementing HIV vaccine trials from the perspective of de facto participants. It aimed to describe the motives and experiences of 31 young adults who participated in a phase II HIV vaccine clinical trial conducted in Maputo, Mozambique. Methods: This was an ancillary study with a mixed-method approach that employed a convergent design, combining both quantitative and qualitative methodologies. Data collection involved questionnaire surveys, in-depth interviews, and focus group discussions. Participants were assessed before and after learning whether they received the experimental vaccine or placebo. Thematic analysis was used for qualitative data, while descriptive analysis and statistical tests such as Fischer's test and McNemar's exact test were applied to quantitative data. The study also utilized the Health Belief Model to understand the decision-making process of participating in an HIV vaccine study. Results: Most of our participants were young females, single, with limited financial resources. Participants joined the trial with the belief that they had a unique opportunity to help the fight against HIV and contribute to the research for the discovery of an HIV vaccine. Positive experiences related to trial participation include gaining knowledge about HIV and personal health and receiving risk reduction counseling. Participants reported blood collection as a negative experience and that they suffered social harm because of trial participation. Participants felt abandoned after the trial ended. Conclusion: Preventive HIV vaccine trials should integrate a social-behavioral component to assess reasons for participation and refusal in real-time. Providing ongoing personal attention is crucial for young individuals who have committed 1-2 years to trial participation, extending beyond the trial period. Implementing tailored strategies for HIV risk assessment and reduction during and after the trial is essential. Addressing these factors can enhance preventive HIV vaccine trial implementation.

Nutritional Prehabilitation in Patients Undergoing Abdominal Surgery-A Narrative Review.

Malnutrition plays a crucial role as a risk factor in patients undergoing major abdominal surgery. To mitigate the risk of complications, nutritional prehabilitation has been recommended for malnourished patients and those at severe metabolic risk. Various approaches have been devised, ranging from traditional short-term conditioning lasting 7-14 days to longer periods integrated into a comprehensive multimodal prehabilitation program. However, a significant challenge is the considerable heterogeneity of nutritional interventions, leading to a lack of clear, synthesizable evidence for specific dietary recommendations. This narrative review aims to outline the concept of nutritional prehabilitation, offers practical recommendations for clinical implementation, and also highlights the barriers and facilitators involved.

Antimicrobial Resistance Surveillance: Data Harmonisation and Data Selection within Secondary Data Use.

Resistance to last-resort antibiotics is a global threat to public health. Therefore, surveillance and monitoring systems for antimicrobial resistance should be established on a national and international scale. For the development of a One Health surveillance system, we collected exemplary data on carbapenem and colistin-resistant bacterial isolates from human, animal, food, and environmental sources. We pooled secondary data from routine screenings, hospital outbreak investigations, and studies on antimicrobial resistance. For a joint One Health evaluation, this study incorporates epidemiological metadata with phenotypic resistance information and molecular data on the isolate level. To harmonise the heterogeneous original information for the intended use, we developed a generic strategy. By defining and categorising variables, followed by plausibility checks, we created a catalogue for prospective data collections and applied it to our dataset, enabling us to perform preliminary descriptive statistical analyses. This study shows the complexity of data management using heterogeneous secondary data pools and gives an insight into the early stages of the development of an AMR surveillance programme using secondary data.

Determinants of p53 DNA binding, gene regulation, and cell fate decisions.

The extent to which transcription factors read and respond to specific information content within short DNA sequences remains an important question that the tumor suppressor p53 is helping us answer. We discuss recent insights into how local information content at p53 binding sites might control modes of p53 target gene activation and cell fate decisions. Significant prior work has yielded data supporting two potential models of how p53 determines cell fate through its target genes: a selective target gene binding and activation model and a p53 level threshold model. Both of these models largely revolve around an analogy of whether p53 is acting in a "smart" or "dumb" manner. Here, we synthesize recent and past studies on p53 decoding of DNA sequence, chromatin context, and cellular signaling cascades to elicit variable cell fates critical in human development, homeostasis, and disease.

Interaction between overconfidence effects and training formats in nurses' education in hand hygiene.

BACKGROUND: Undergraduate training in hand hygiene is a keystone of infection control. Several studies have shown overconfidence effects in hand hygiene practices, which can impair metacognition. We hypothesized that overconfidence might be prevalent in the early education stages of nursing students and that these effects could be reduced through frequent interactive learning formats, such as learning groups. METHODS: We conducted a multicenter cross-sectional questionnaire with 196 German nursing students, including general, surgical, and anesthetic nursing specializations. RESULTS: Overconfidence was observed in nursing students across all specialties and years of education. The cluster analyses showed three different types of learners: two characterized by overconfidence and one demonstrating justifiable confidence. Furthermore, the moderation analysis indicated that providing feedback and promoting metacognition regarding students' learning achievements could mitigate overplacement, particularly through the frequent implementation of interactive teaching formats. DISCUSSION: Despite some limitations, these findings highlight the prevalence of overconfidence effects in nursing students, the presence of different learning profiles, and the importance of incorporating feedback within interactive learning formats concerning hand hygiene. Accordingly, educators need to be trained and supervised to deliver these learning formats and provide feedback to students effectively.

A cross-cultural comparison of finger-based and symbolic number representations.

The current study examined predictions from embodied cognition for effects of finger counting on number processing. Although finger counting is spontaneous and nearly universal, counting habits reflect learning and culture. European cultures use a sub-base-five system, requiring a full hand plus additional fingers to express numbers exceeding 5. Chinese culture requires only one hand to express such numbers. We investigated the differential impact of early-acquired finger-based number representations on adult symbolic number processing. In total, 53 European and 56 Chinese adults performed two versions of the magnitude classification task, where numbers were presented either as Arabic symbols or as finger configurations consistent with respective cultural finger-counting habits. Participants classified numbers as smaller/larger than 5 with horizontally aligned buttons. Finger-based size and distance effects were larger in Chinese compared with Europeans. These differences did not, however, induce reliably different symbol processing signatures. This dissociation challenges the idea that sensory and motor habits shape our conceptual representations and implies notation-specific processing patterns.

On the embodied nature of knowledge: From neurons to numbers.

Interdisciplinary investigations of the human mind through the cognitive sciences have identified a key role of the body in representing knowledge. After characterizing knowledge at grounded, embodied, and situated levels, number knowledge is analyzed from this hierarchical perspective. Lateralized cortical processing of coarse versus fine detail is identified as a grounding substrate for the population stereotype few/left, many/right, which then contributes to number-related sensory and motor biases at the embodied and situated levels. Implications of this perspective for education and rehabilitation are discussed.

Minimally destructive hDNA extraction method for retrospective genetics of pinned historical Lepidoptera specimens.

The millions of specimens stored in entomological collections provide a unique opportunity to study historical insect diversity. Current technologies allow to sequence entire genomes of historical specimens and estimate past genetic diversity of present-day endangered species, advancing our understanding of anthropogenic impact on genetic diversity and enabling the implementation of conservation strategies. A limiting challenge is the extraction of historical DNA (hDNA) of adequate quality for sequencing platforms. We tested four hDNA extraction protocols on five body parts of pinned false heath fritillary butterflies, Melitaea diamina, aiming to minimise specimen damage, preserve their scientific value to the collections, and maximise DNA quality and yield for whole-genome re-sequencing. We developed a very effective approach that successfully recovers hDNA appropriate for short-read sequencing from a single leg of pinned specimens using silica-based DNA extraction columns and an extraction buffer that includes SDS, Tris, Proteinase K, EDTA, NaCl, PTB, and DTT. We observed substantial variation in the ratio of nuclear to mitochondrial DNA in extractions from different tissues, indicating that optimal tissue choice depends on project aims and anticipated downstream analyses. We found that sufficient DNA for whole genome re-sequencing can reliably be extracted from a single leg, opening the possibility to monitor changes in genetic diversity maintaining the scientific value of specimens while supporting current and future conservation strategies.

Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023.

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-ß-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1-carrying-P. stuartii and the third bla NDM-5-carrying-P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10, bla CMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.

The genes mgtE and spoVG are involved in zinc tolerance of Staphylococcus aureus.

Metals are essential for all living organisms, but the type of metal and its concentration determines its action. Even low concentrations of metals may have toxic effects on organisms and therefore exhibit antimicrobial activities. In this study, we investigate the evolutionary adaptation processes of Staphylococcus aureus to metals and common genes for metal tolerance. Laboratory and clinical isolates were treated with manganese, cobalt, zinc, or nickel metal salts to generate growth-adapted mutants. After growth in medium supplemented with zinc, whole-genome sequencing identified, among others, two genes, mgtE (SAUSA300_0910), a putative magnesium transporter and spoVG (SAUSA300_0475), a global transcriptional regulator, as hot spots for stress-induced single-nucleotide polymorphisms (SNPs). SNPs in mgtE were also detected in mutants treated with high levels of cobalt or nickel salts. To investigate the effect of these genes on metal tolerance, deletion mutants and complementation strains in an S. aureus USA300 LAC* laboratory strain were generated. Both, the mgtE and spoVG deletion strains were more tolerant to cobalt, manganese, and zinc. The mgtE mutant was also more tolerant to nickel exposure. Inductively coupled plasma mass spectrometry analysis demonstrated that the mgtE deletion mutant accumulated less intracellular zinc than the wild type, explaining increased tolerance. From these results, we conclude that mgtE gene inactivation increases zinc tolerance presumably due to reduced uptake of zinc. For the SpoVG mutant, no direct effect on the intracellular zinc concentration was detected, indicating toward different pathways to increase tolerance. Importantly, inactivation of these genes offers a growth advantage in environments containing certain metals, pointing toward a common tolerance mechanism. IMPORTANCE: Staphylococcus aureus is an opportunistic pathogen causing tremendous public health burden and high mortality in invasive infections. Treatment is becoming increasingly difficult due to antimicrobial resistances. The use of metals in animal husbandry and aquaculture to reduce bacterial growth and subsequent acquisition of metal resistances has been shown to co-select for antimicrobial resistance. Therefore, understanding adaptive mechanisms that help S. aureus to survive metal exposure is essential. Using a screening approach, we were able to identify two genes encoding the transporter MgtE and the transcriptional regulator SpoVG, which conferred increased tolerance to specific metals such as zinc when inactivated. Further testing showed that the deletion of mgtE leads to reduced intracellular zinc levels, suggesting a role in zinc uptake. The accumulation of mutations in these genes when exposed to other metals suggests that inactivation of these genes could be a common mechanism for intrinsic tolerance to certain metals.