Sleep, psychological health, and physical activity level in patients with hypertension.

The aim of this study was to compare sleep, daytime sleepiness, and psychological health in physically active versus inactive patients with hypertension. A cross-sectional design included thirty-seven participants (ACTIVE, n = 15; INACTIVE, n = 22). Sleep was assessed by polysomnography, the Pittsburgh Sleep Quality Index (PSQI) and a one-week daily sleep diary. The sleepiness was assessed with the Epworth Sleepiness Scale and the psychological health was assessed with the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Profile of Mood States (POMS). Habitual physical activity was assessed with 7 day-step counts recorded by a pedometer and questionnaire. Significantly lower PSQI score (mean ± S.D.; 7.3 ± 3.4 vs 10.1 ± 3.6) and daytime sleepiness (8.7 ± 4.5 vs. 11.9 ± 4.4) were found in the physically active versus inactive participants, respectively. In addition, higher PSQI-total sleep time (6.9 ± 1.3 vs 5.6 ± 1.1) and vigor/activity (19.7 ± 3.9 vs 16.0 ± 3.9), and lower depressed mood on the POMS scale (8.2 ± 7.9 vs 13.8 ± 10.0) and lower POMS total mood disturbance (21.0 ± 27.0 vs 43.5 ± 32.5) were observed in the active participants compared with the inactive participants. Combining data across both groups, leisure time sport participation correlated negatively with PSQI (r = -0.35; p < 0.05) and BDI (r = -0.42; p < 0.05), and positively with POMS-vigor/activity (r = 0.43; p < 0.05). The results showed regular physical activity was associated with better sleep and psychological health in patients with hypertension.

Synthesis of polymeric nanoparticles by double emulsion and pH-driven: encapsulation of antibiotics and natural products for combating Escherichia coli infections.

The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its broad applicability. Polymeric nanoparticle synthesis employs advanced techniques such as the double emulsion approach and the pH-driven method, allowing the efficient incorporation of active compounds into these matrices. These loading methods ensure compound stability within the polymeric structure and enable control of the release of therapeutic agents. The ability of loaded polymeric nanoparticles to transport and release therapeutic agents on target manner represents a significant advancement in the quest for effective therapeutic solutions. Amid escalating concerns regarding antimicrobial resistance, interventions using polymeric nanostructures stand out for the possibility of carrying antimicrobial agents and enhancing antibacterial action against antibiotic-resistant bacteria, making a new therapeutic approach or complement to conventional treatments. In this sense, the capability of these polymeric nanoparticles to act against Escherichia coli underscores their relevance in controlling bacterial infections. This mini-review provides a comprehensive synthesis of promising techniques for loading therapeutic agents into polymeric nanoparticles highlighting methodologies and their implications, addressing prospects of combating bacterial infections caused by E. coli. KEY POINTS: • The double emulsion method provides control over size and release of bioactives. • The pH-driven method improves the solubility, stability, and release of active. • The methods increase the antibacterial action of those encapsulated in PNPs.

Molecular characterization of the interaction between human IgG and the M-related proteins from Streptococcus pyogenes.

Group A Streptococcal M-related proteins (Mrps) are dimeric α-helical-coiled-coil cell membrane-bound surface proteins. During infection, Mrp recruit the fragment crystallizable region of human immunoglobulin G via their A-repeat regions to the bacterial surface, conferring upon the bacteria enhanced phagocytosis resistance and augmented growth in human blood. However, Mrps show a high degree of sequence diversity, and it is currently not known whether this diversity affects the Mrp-IgG interaction. Herein, we report that diverse Mrps all bind human IgG subclasses with nanomolar affinity, with differences in affinity which ranged from 3.7 to 11.1 nM for mixed IgG. Using surface plasmon resonance, we confirmed Mrps display preferential IgG-subclass binding. All Mrps were found to have a significantly weaker affinity for IgG3 (p < 0.05) compared to all other IgG subclasses. Furthermore, plasma pulldown assays analyzed via Western blotting revealed that all Mrp were able to bind IgG in the presence of other serum proteins at both 25 °C and 37 °C. Finally, we report that dimeric Mrps bind to IgG with a 1:1 stoichiometry, enhancing our understanding of this important host-pathogen interaction.

Effects of two years of physically active lessons on cognitive indicators in children.

Our purpose was to evaluate the effect of physically active lessons (PAL) on the cognitive performance of children during two years of follow-up. Four classes (second grade of elementary school) were divided into two intervention classes (n = 34) and two control classes (n = 27). Evaluations were performed before the intervention (M1), after 3 (M2) and 9 (M3) months in the 1st year, and 14 (M4) and 18 (M5) months in the 2nd year. The intervention was based on PAL integrated with the curricular components, which stimulated the children to stand or move in the classroom. Cognitive performance was evaluated using three computerized tests for response inhibition, selective attention, and cognitive flexibility. The children in the intervention classes presented improved cognitive performance in the execution of all tasks along the two years follow-up, in both correct answers and time reactions, with exception of correct answers of visual search. For the intervention classes, in most of the tasks, the mean differences confidence interval of 95% did not include the 0 on the two last moments of evaluation, and in all cases, the mean differences of them between M1 versus M5 were significantly different with high values of effect size (cohen -d > 1). PAL promotes modest improvements in diverse cognitive functions in children.

Effects of exercise training on glucocorticoid-induced muscle atrophy: Literature review.

Glucocorticoids (GCs) administration, such as cortisol acetate (CA) and dexamethasone (DEXA), is used worldwide due to their anti-inflammatory, anti-allergic, and immunosuppressive properties. However, muscle atrophy is one of the primary deleterious induced responses from the chronic treatment with GCs since it stimulates muscle degradation inhibiting muscle protein synthesis. Animal models allow a better understanding of the molecular pathways involved in this process of gene modulation and production of hypertrophic and atrophic proteins. The treatment with GCs, such as DEXA, promotes the reduction of hypertrophic proteins such as serine/threonine tyrosine kinase (AKT), protein kinase mammalian target of rapamycin (mTOR), and ribosomal protein S6 kinase (p70S6K) and increased gene expression or production of atrophic proteins, such as myostatin, muscle atrophic F-box (atrogin-1), or muscle ring finger protein-1 (MuRF-1). In both continuous exercise (CE) and resistance exercise (RE) forms, exercise training is used to mitigate muscle atrophy induced by GCs. The CE attenuated muscle atrophy induced by CA or DEXA in the plantaris and extensor digitorum longus muscles, while RE mitigated the DEXA-induced atrophy in plantaris and flexor hallucis longus muscles. The RE response appears to have occurred by modulation of hypertrophic proteins through increased protein production or phosphorylated/total ratio of mTOR and p70S6K and decreased atrophic protein production of MuRF-1. CE needs future research to understand the molecular pathways of its protective response.

Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria.

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research.

Pathogenesis, epidemiology and control of Group A Streptococcus infection.

Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. Fluctuating global GAS epidemiology is characterized by the emergence of new GAS clones, often associated with the acquisition of new virulence or antimicrobial determinants that are better adapted to the infection niche or averting host immunity. The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. The World Health Organization (WHO) has developed a GAS research and technology road map and has outlined preferred vaccine characteristics, stimulating renewed interest in the development of safe and effective GAS vaccines.

Detection of Streptococcus pyogenes M1UK in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA.

A new variant of Streptococcus pyogenes serotype M1 (designated 'M1UK') has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor S. pyogenes 'M1global' and M1UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1UK in Australia, now isolated from the majority of serious infections caused by serotype M1 S. pyogenes. M1UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing S. pyogenes in Asia. A single SNP in the 5' transcriptional leader sequence of the transfer-messenger RNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator read-through in the M1UK lineage. This represents a previously unappreciated mechanism of toxin expression and urges enhanced international surveillance.

How Personalization Affects Motivation in Gamified Review Assessments.

Personalized gamification aims to address shortcomings of the one-size-fits-all (OSFA) approach in improving students' motivations throughout the learning process. However, studies still focus on personalizing to a single user dimension, ignoring multiple individual and contextual factors that affect user motivation. Unlike prior research, we address this issue by exploring multidimensional personalization compared to OSFA based on a multi-institution sample. Thus, we conducted a controlled experiment in three institutions, comparing gamification designs (OSFA and Personalized to the learning task and users' gaming habits/preferences and demographics) in terms of 58 students' motivations to complete assessments for learning. Our results suggest no significant differences among OSFA and Personalized designs, despite suggesting user motivation depended on fewer user characteristics when using personalization. Additionally, exploratory analyses suggest personalization was positive for females and those holding a technical degree, but negative for those who prefer adventure games and those who prefer single-playing. Our contribution benefits designers, suggesting how personalization works; practitioners, demonstrating to whom the personalization strategy was more or less suitable; and researchers, providing future research directions. Supplementary Information: The online version contains supplementary material available at 10.1007/s40593-022-00326-x.

Early Cretaceous Ostracoda (Crustacea) from south-central Araripe Basin, Brazil, with descriptions of seven new species.

A systematic study is made of Early Cretaceous (late Aptian/earlyAlbian) ostracod assemblages from the Santo Antnio section. This section is characterized by sediment belonging to the post-rift sedimentary sequence of the Romualdo Formation in the southern-central region of the Araripe Basin, Brazil and represents on of the first marine ingression in the interior of the continent, during the beginning of the formation of the Atlantic Ocean. The Santo Antonio section presents ostracods in greater diversity than previously known. Nineteen samples were analyzed, yielding a total of 8,370 specimens. Fifteen taxa were identified, including six brackish ostracods: Pattersoncypris salitrensis, Pattersoncypris angulata, Pattersoncypris micropapillosa, Damonella grandiensis, Alicenula cf. leguminella and Theriosynoecum cf. quadrinodosum; and nine typically brackish-marine species, including seven new ones: Dicrorygma cf. minuta, Dicrorygma (Orthorygma?) dimorpha, Mongolianella aptianensis sp. nov., Mantelliana speculum sp. nov., Paracypris undulareventralis sp. nov., Microceratina retangularis sp. nov., Perissocytheridea oculusutilis sp. nov., Perissocytheridea poruslinearis sp. nov. and Perissocytheridea florisdorsalis sp. nov. Therefore, the detailed taxonomic study brings a new understanding of marine ostracods around the upper Aptian/lower Albian boundary of the Araripe Basin.

Streptococcus pyogenes Hijacks Host Glutathione for Growth and Innate Immune Evasion.

The nasopharynx and the skin are the major oxygen-rich anatomical sites for colonization by the human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]). To establish infection, GAS must survive oxidative stress generated during aerobic metabolism and the release of reactive oxygen species (ROS) by host innate immune cells. Glutathione is the major host antioxidant molecule, while GAS is glutathione auxotrophic. Here, we report the molecular characterization of the ABC transporter substrate binding protein GshT in the GAS glutathione salvage pathway. We demonstrate that glutathione uptake is critical for aerobic growth of GAS and that impaired import of glutathione induces oxidative stress that triggers enhanced production of the reducing equivalent NADPH. Our results highlight the interrelationship between glutathione assimilation, carbohydrate metabolism, virulence factor production, and innate immune evasion. Together, these findings suggest an adaptive strategy employed by extracellular bacterial pathogens to exploit host glutathione stores for their own benefit. IMPORTANCE During infection, microbes must escape host immune responses and survive exposure to reactive oxygen species produced by immune cells. Here, we identify the ABC transporter substrate binding protein GshT as a key component of the glutathione salvage pathway in glutathione-auxotrophic GAS. Host-acquired glutathione is crucial to the GAS antioxidant defense system, facilitating escape from the host innate immune response. This study demonstrates a direct link between glutathione assimilation, aerobic metabolism, and virulence factor production in an important human pathogen. Our findings provide mechanistic insight into host adaptation that enables extracellular bacterial pathogens such as GAS to exploit the abundance of glutathione in the host cytosol for their own benefit.

Neurodegenerative Disease Treatment Drug PBT2 Breaks Intrinsic Polymyxin Resistance in Gram-Positive Bacteria.

Gram-positive bacteria do not produce lipopolysaccharide as a cell wall component. As such, the polymyxin class of antibiotics, which exert bactericidal activity against Gram-negative pathogens, are ineffective against Gram-positive bacteria. The safe-for-human-use hydroxyquinoline analog ionophore PBT2 has been previously shown to break polymyxin resistance in Gram-negative bacteria, independent of the lipopolysaccharide modification pathways that confer polymyxin resistance. Here, in combination with zinc, PBT2 was shown to break intrinsic polymyxin resistance in Streptococcus pyogenes (Group A Streptococcus; GAS), Staphylococcus aureus (including methicillin-resistant S. aureus), and vancomycin-resistant Enterococcus faecium. Using the globally disseminated M1T1 GAS strain 5448 as a proof of principle model, colistin in the presence of PBT2 + zinc was shown to be bactericidal in activity. Any resistance that did arise imposed a substantial fitness cost. PBT2 + zinc dysregulated GAS metal ion homeostasis, notably decreasing the cellular manganese content. Using a murine model of wound infection, PBT2 in combination with zinc and colistin proved an efficacious treatment against streptococcal skin infection. These findings provide a foundation from which to investigate the utility of PBT2 and next-generation polymyxin antibiotics for the treatment of Gram-positive bacterial infections.

An ionophore breaks the multi-drug-resistance of Acinetobacter baumannii.

Within intensive care units, multi-drug resistant Acinetobacter baumannii outbreaks are a frequent cause of ventilator-associated pneumonia. During the on-going COVID-19 pandemic, patients who receive ventilator support experience a 2-fold increased risk of mortality when they contract a secondary A. baumannii pulmonary infection. In our recent paper (De Oliveira et al. (2022), Mbio, doi: 10.1128/mbio.03517-21), we demonstrate that the 8-hydroxquinoline ionophore, PBT2 breaks the resistance of A. baumannii to tetracycline class antibiotics. In vitro, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multi-drug-resistant A. baumannii, and any resistance that did arise imposed a fitness cost. Using a murine model of pulmonary infection, treatment with PBT2 in combination with tetracycline or tigecycline proved efficacious against multidrug-resistant A. baumannii. These findings suggest that PBT2 may find utility as a resistance breaker to rescue the efficacy of tetracycline-class antibiotics commonly employed to treat multi-drug resistant A. baumannii infections.

Dysregulation of Streptococcus pneumoniae zinc homeostasis breaks ampicillin resistance in a pneumonia infection model.

Streptococcus pneumoniae is the primary cause of community-acquired bacterial pneumonia with rates of penicillin and multidrug-resistance exceeding 80% and 40%, respectively. The innate immune response generates a variety of antimicrobial agents to control infection, including zinc stress. Here, we characterize the impact of zinc intoxication on S. pneumoniae, observing disruptions in central carbon metabolism, lipid biogenesis, and peptidoglycan biosynthesis. Characterization of the pivotal peptidoglycan biosynthetic enzyme GlmU indicates a sensitivity to zinc inhibition. Disruption of the sole zinc efflux pathway, czcD, renders S. pneumoniae highly susceptible to ß-lactam antibiotics. To dysregulate zinc homeostasis in the wild-type strain, we investigated the safe-for-human-use ionophore 5,7-dichloro-2-[(dimethylamino)methyl]quinolin-8-ol (PBT2). PBT2 rendered wild-type S. pneumoniae strains sensitive to a range of antibiotics. Using an invasive ampicillin-resistant strain, we demonstrate in a murine pneumonia infection model the efficacy of PBT2 + ampicillin treatment. These findings present a therapeutic modality to break antibiotic resistance in multidrug-resistant S. pneumoniae.

Rescuing Tetracycline Class Antibiotics for the Treatment of Multidrug-Resistant Acinetobacter baumannii Pulmonary Infection.

Acinetobacter baumannii causes high mortality in ventilator-associated pneumonia patients, and antibiotic treatment is compromised by multidrug-resistant strains resistant to ß-lactams, carbapenems, cephalosporins, polymyxins, and tetracyclines. Among COVID-19 patients receiving ventilator support, a multidrug-resistant A. baumannii secondary infection is associated with a 2-fold increase in mortality. Here, we investigated the use of the 8-hydroxyquinoline ionophore PBT2 to break the resistance of A. baumannii to tetracycline class antibiotics. In vitro, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multidrug-resistant A. baumannii, and any resistance that did arise imposed a fitness cost. PBT2 and zinc disrupted metal ion homeostasis in A. baumannii, increasing cellular zinc and copper while decreasing magnesium accumulation. Using a murine model of pulmonary infection, treatment with PBT2 in combination with tetracycline or tigecycline proved efficacious against multidrug-resistant A. baumannii. These findings suggest that PBT2 may find utility as a resistance breaker to rescue the efficacy of tetracycline-class antibiotics commonly employed to treat multidrug-resistant A. baumannii infections. IMPORTANCE Within intensive care unit settings, multidrug-resistant (MDR) Acinetobacter baumannii is a major cause of ventilator-associated pneumonia, and hospital-associated outbreaks are becoming increasingly widespread. Antibiotic treatment of A. baumannii infection is often compromised by MDR strains resistant to last-resort ß-lactam (e.g., carbapenems), polymyxin, and tetracycline class antibiotics. During the on-going COVID-19 pandemic, secondary bacterial infection by A. baumannii has been associated with a 2-fold increase in COVID-19-related mortality. With a rise in antibiotic resistance and a reduction in new antibiotic discovery, it is imperative to investigate alternative therapeutic regimens that complement the use of current antibiotic treatment strategies. Rescuing the efficacy of existing therapies for the treatment of MDR A. baumannii infection represents a financially viable pathway, reducing time, cost, and risk associated with drug innovation.

Active Vegetarians Show Better Lower Limb Strength and Power than Active Omnivores.

Vegetarian diets have become popular among athletes and active individuals and can have advantages for physical performance, but the results are still conflicting regarding muscle strength and power. The aim of this study was to evaluate the diet and physical performance of vegetarians through tests of dynamic, isometric, and relative strength; muscle power; and aerobic capacity. In this cross-sectional study, 32 vegetarians and 26 omnivores, who were physically active, were evaluated for the Healthy Eating Index and performance tested back squat, handgrip strength, isometric deadlift strength, jump with countermovement, and maximum aerobic speed (MAS). Improved diet quality (63.24±14.40 vs. 54±16.80, p<0.05), greater relative strength (1.03±0.23 vs. 0.91±0.12, p<0.05), and greater jump height (43.77±9.91 vs. 38.45±8.92, p<0.05) were found among vegetarians. No difference was seen in MAS (13.5±2 vs. 11±3, p>0.05) or isometric strength of upper limbs (77±29 vs. 70±50, p>0.05) and lower limbs (89±41 vs. 97±50, p>0.05). Thus, we conclude that vegetarians and omnivores show similar performance in strength and aerobic capacity, but in our sample, vegetarians show higher levels of relative strength and power.

Effect of dietary plants on the production of immunoglobulins A in healthy Wistar rats / Efeito de plantas dietéticas na produção de imunoglobulinas A em ratos Wistar saudáveis

Introduction: some plants such as turmeric, cinnamon, and okra are known to have therapeutic functions such as antioxidant and anti-inflammatory activity. Furthermore, an immunomodulatory role has been observed in the production of antibodies, in particular immunoglobulin A (IgA), which mediates a variety of protective functions for the organism. Objective: the aim of the present study was to investigate the effect of dietary plants on the production of IgA in healthy Wistar rats. Methods: thus, 48 male Wistar rats of 90 days of age were allocated to four groups. The animals were treated for 14 days with dried turmeric, cinnamon, or okra (50, 50, 12.5 mg/day, respectively) in phosphate buffered saline, or with only phosphate buffered saline by gavage. The animals received water and feed ad libitum. Body mass and relative weight ofperitoneal fat, adrenal gland, kidney, spleen, liver and thymus, biochemical parameters, and IgA levels were analyzed. Results: no significant changes were observed in the body mass, relative weight of organs and tissues, and biochemical parameters. An increase in serum IgA levels was observed in animals treated with turmeric or cinnamon. Conclusion: we conclude that the treatment with turmeric and cinnamon increased IgA production. Therefore, our study supports the idea that dietary supplementation with these plants may improve humoral immunity.

Introdução: algumas plantas como a cúrcuma, a canela e o quiabo são conhecidas por apresentar funções terapêuticas, como atividade antioxidante e anti-inflamatória. Além disso, tem sido observado um papel imunomodulador sobre a produção de anticorpos, em especial a imunoglobulina A (IgA), a qual medeia uma variedade de funções protetoras para o organismo. Objetivo: o objetivo do presente estudo foi investigar o efeito de plantas dietéticas na produção de IgA em ratos Wistar saudáveis. Métodos: destarte, 48 ratos machos Wistar com 90 dias de idade foram alocados em quatro grupos. Os animais foram tratados por 14 dias com cúrcuma seca, canela ou quiabo (50, 50, 12,5 mg/dia, respectivamente) em solução salina tamponada com fosfato ou apenas solução salina tamponada com fosfato, por gavagem. Os animais receberam água e ração ad libitum. Foram analisados a massa corporal e o peso relativo da gordura peritoneal, glândula adrenal, rim, baço, fígado e timo, parâmetros bioquímicos e níveis de IgA. Resultados: não foram observadas alterações significativas na massa corporal, no peso relativo dos órgãos e tecidos e nos parâmetros bioquímicos. Foi observado aumento dos níveis séricos de IgA nos animais tratados com cúrcuma ou canela. Conclusão: podemos concluir que o tratamento com cúrcuma e canela aumentou a produção de IgA. Portanto, nosso estudo suporta a ideia de que a suplementação alimentar com essas plantas pode melhorar a imunidade humoral.

Strengths and caveats of identifying resistance genes from whole genome sequencing data.

INTRODUCTION: Antimicrobial resistance (AMR) continues to present major challenges to modern healthcare. Recent advances in whole-genome sequencing (WGS) have made the rapid molecular characterization of AMR a realistic possibility for diagnostic laboratories; yet major barriers to clinical implementation exist. AREAS COVERED: We describe and compare short- and long-read sequencing platforms, typical components of bioinformatics pipelines, tools for AMR gene detection and the relative merits of read- or assembly-based approaches. The challenges of characterizing mobile genetic elements from genomic data are outlined, as well as the complexities inherent to the prediction of phenotypic resistance from WGS. Practical obstacles to implementation in diagnostic laboratories, the critical role of quality control and external quality assurance, as well as standardized reporting standards are also discussed. Future directions, such as the application of machine-learning and artificial intelligence algorithms, linked to clinically meaningful outcomes, may offer a new paradigm for the clinical application of AMR prediction. EXPERT OPINION: AMR prediction from WGS data presents an exciting opportunity to advance our capacity to comprehensively characterize infectious pathogens in a rapid manner, ultimately aiming to improve patient outcomes. Collaborative efforts between clinicians, scientists, regulatory bodies and healthcare administrators will be critical to achieve the full promise of this approach.

The antimicrobial and immunomodulatory effects of Ionophores for the treatment of human infection.

Ionophores are a diverse class of synthetic and naturally occurring ion transporter compounds which demonstrate both direct and in-direct antimicrobial properties against a broad panel of bacterial, fungal, viral and parasitic pathogens. In addition, ionophores can regulate the host-immune response during communicable and non-communicable disease states. Although the clinical use of ionophores such as Amphotericin B, Bedaquiline and Ivermectin highlight the utility of ionophores in modern medicine, for many other ionophore compounds issues surrounding toxicity, bioavailability or lack of in vivo efficacy studies have hindered clinical development. The antimicrobial and immunomodulating properties of a range of compounds with characteristics of ionophores remain largely unexplored. As such, ionophores remain a latent therapeutic avenue to address both the global burden of antimicrobial resistance, and the unmet clinical need for new antimicrobial therapies. This review will provide an overview of the broad-spectrum antimicrobial and immunomodulatory properties of ionophores, and their potential uses in clinical medicine for combatting infection.