gcPathogen: a comprehensive genomic resource of human pathogens for public health.

Here, we present the manually curated Global Catalogue of Pathogens (gcPathogen), an extensive genomic resource designed to facilitate rapid and accurate pathogen analysis, epidemiological exploration and monitoring of antibiotic resistance features and virulence factors. The catalogue seamlessly integrates and analyzes genomic data and associated metadata for human pathogens isolated from infected patients, animal hosts, food and the environment. The pathogen list is supported by evidence from medical or government pathogenic lists and publications. The current version of gcPathogen boasts an impressive collection of 1 164 974 assemblies comprising 986 044 strains from 497 bacterial taxa, 4794 assemblies encompassing 4319 strains from 265 fungal taxa, 89 965 assemblies featuring 13 687 strains from 222 viral taxa, and 646 assemblies including 387 strains from 159 parasitic taxa. Through this database, researchers gain access to a comprehensive 'one-stop shop' that facilitates global, long-term public health surveillance while enabling in-depth analysis of genomes, sequence types, antibiotic resistance genes, virulence factors and mobile genetic elements across different countries, diseases and hosts. To access and explore the data and statistics, an interactive web interface has been developed, which can be accessed at https://nmdc.cn/gcpathogen/. This user-friendly platform allows seamless querying and exploration of the extensive information housed within the gcPathogen database.

Microbial Primer: In vivo biofilm.

In this primer on biofilms and their role in infections, we trace the historical roots of microbial understanding from Van Leeuwenhoek's observations to Bill Costerton's groundbreaking work, which solidified biofilms' significance in infections. In vivo biofilm research, investigating patient samples and utilizing diverse host models, has yielded invaluable insights into these complex microbial communities. However, it comes with several challenges, particularly regarding replicating biofilm infections accurately in the laboratory. In vivo biofilm analyses involve various techniques, revealing biofilm architecture, composition, and behaviour, while gaps in knowledge persist regarding infection initiation and source, diversity, and the Infectious Microenvironment (IME). Ultimately, the study of biofilms in infections remains a dynamic and evolving field poised to transform our approach to combat biofilm-associated diseases.

Overview of game meat utilisation challenges and opportunities: A European perspective.

Re-wilding and similar initiatives have resulted in an increase in wildlife suitable for human consumption in Europe. However, game meat production and consumption present several challenges, including infectious diseases which pose risks to livestock, processers, and consumers. This review provides insights into the infectious diseases and toxic contaminants associated with game meat. The effect of killing method on the meat quality is also discussed and means of improving the meat quality of game meat is elucidated. The use of different food safety systems that could be applied to provide safe meat is reported. The importance of collaborative multi-sector approaches is emphasized, to generate and distribute knowledge and implement One Health strategies that ensure the safe, traceable, sustainable, and professional development of commercial game meat supply chains.

As Superbugs Flourish, Bacteriophage Therapy Recaptures Researchers' Interest.

This Medical News article discusses the resurgence of phage therapy research for antibiotic-resistant infections.

Analysis of the Toll and Spaetzle Genes Involved in Toll Pathway-Dependent Antimicrobial Gene Induction in the Red Flour Beetle, Tribolium castaneum (Coleoptera; Tenebrionidae).

Insects rely only on their innate immune system to protect themselves from pathogens. Antimicrobial peptide (AMP) production is the main immune reaction in insects. In Drosophila melanogaster, the reaction is regulated mainly by the Toll and immune deficiency (IMD) pathways. Spaetzle proteins, activated by immune signals from upstream components, bind to Toll proteins, thus, activating the Toll pathway, which in turn, induces AMP genes. Previous studies have shown the difference in immune systems related to Toll and IMD pathways between D. melanogaster and Tribolium castaneum. In T. castaneum, nine Toll and seven spaetzle (spz) genes were identified. To extend our understanding of AMP production by T. castaneum, we conducted functional assays of Toll and spaetzle genes related to Toll-pathway-dependent AMP gene expression in T. castaneum under challenge with bacteria or budding yeast. The results revealed that Toll3 and Toll4 double-knockdown and spz7 knockdown strongly and moderately reduced the Toll-pathway-dependent expression of AMP genes, respectively. Moreover, Toll3 and Toll4 double-knockdown pupae more rapidly succumbed to entomopathogenic bacteria than the control pupae, but spz7 knockdown pupae did not. The results suggest that Toll3 and Toll4 play a large role in Toll-pathway-dependent immune reactions, whereas spz7 plays a small part.

Remembrance of infections past.

Host-derived metabolite trains the microbiota to develop colonization resistance.

Highlights of infectious agents in tissue.

The evolution of the diagnosis of infectious diseases began with the observation of the morphological characteristics of organisms such as ascaris and whipworms, followed by the use of the microscope and haematoxylin and eosin stains, which allowed recognition of microscopic characteristics undetectable with the naked eye, such as the viral cytopathic changes of herpes and the presence of fungi. Patterns of acute and chronic granulomatous inflammation were also observed; these were not specific to the exact aetiology of the disease, which led to the introduction of special methenamine stains for fungi and Ziehl-Neelsen for fungi and mycobacteria. Later, the use of immunohistochemistry was introduced, which acknowledged the use of antibodies to classify microorganisms and detect cases that were either difficult to interpret or in the midst of severe inflammatory processes. Currently, the use of molecular biology has made it possible to reach diagnoses that would have been very difficult to obtain through traditional methods; these techniques show key specific characteristics and facilitate the diagnosis of various infectious pathologies. These new techniques are based on the detection of antigens and nucleic acids of microorganisms, an important advance in the diagnosis of infectious diseases.

Organoids in modelling infectious diseases.

Approaches based on animal and two-dimensional (2D) cell culture models cannot ensure reliable results in modeling novel pathogens or in drug testing in the short term; therefore, there is rising interest in platforms such as organoids. To develop a toolbox that can be used successfully to overcome current issues in modeling various infections, it is essential to provide a framework of recent achievements in applying organoids. Organoids have been used to study viruses, bacteria, and protists that cause, for example, respiratory, gastrointestinal, and liver diseases. Their future as models of infection will be associated with improvements in system complexity, including abilities to model tissue structure, a dynamic microenvironment, and coinfection. Teaser. Organoids are a flexible tool for modelling viral, bacterial and protist infections. They can provide fast and reliable information on the biology of pathogens and in drug screening, and thus have become essential in combatting emerging infectious diseases.

Antimicrobial blue light: A 'Magic Bullet' for the 21st century and beyond?

Over the past decade, antimicrobial blue light (aBL) at 400 - 470 nm wavelength has demonstrated immense promise as an alternative approach for the treatment of multidrug-resistant infections. Since our last review was published in 2017, there have been numerous studies that have investigated aBL in terms of its, efficacy, safety, mechanism, and propensity for resistance development. In addition, researchers have looked at combinatorial approaches that exploit aBL and other traditional and non-traditional therapeutics. To that end, this review aims to update the findings from numerous studies that capitalize on the antimicrobial effects of aBL, with a focus on: efficacy of aBL against different microbes, identifying endogenous chromophores and targets of aBL, Resistance development to aBL, Safety of aBL against host cells, and Synergism of aBL with other agents. We will also discuss our perspective on the future of aBL.

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.

Prevalence and Clinical Significance of Occult Pulmonary Infection in Elderly Patients with Type 2 Diabetes Mellitus.

The occult pulmonary infection is the most common complications in elderly patients with type 2 diabetes mellitus (T2DM). Since its etiological characteristics has not been clarified, infection control remains a serious problem for public health. To investigate the prevalence and clinical significance of occult pulmonary infection in elderly T2DM patients, in this study, 573 elderly patients cochallenged with T2DM and community-acquired pulmonary infection from January 2018 to December 2020 were selected in the hospitals and divided into occult pneumonia group (OP, n = 249) and nonoccult pneumonia group (NOP, n = 324) according to the nature of infection. Clinical medical records were analyzed retrospectively to summarize the infection characteristics of elderly diabetics with occult pneumonia. The prevalence of the cases (278/324, 85.8%) in NOP group was not higher than that in OP group (206/249, 82.7%; P > 0.05). Also, there was not significant difference in the distribution of isolated pathogens among the positive patients. The length of hospitalization and mortality of OP patients were significantly higher than those NOP patients. Multivariate logistic regression showed that advanced age, comorbidities, hypothyroidism, senile dementia, and prolonged bed rest were independent risk factors for occult pneumonia in elderly diabetic patients. Therefore, the results demonstrated that the pulmonary infection in elderly patients with diabetes mellitus is often occult. Gram-negative bacteria are the predominant pathogens and cause poor prognosis. Advanced age, comorbidities (senile dementia, hypothyroidism), and prolonged bed rest are the independent risk factors for occult pneumonia.

Infection risks related to aesthetic procedures: microbial profile and professional perception about infection prevention measures / Riscos de infecção relacionados a procedimentos estéticos: perfil microbiano e percepção profissional sobre medidas de prevenção de infecção / Riesgos de infección relacionados con los procedimientos estéticos: perfil microbiano y percepción profesional sobre las medidas de prevención de infecciones

Background and Objectives: This study aimed to identify the presence of microorganisms in the aesthetic environment and assess professionals' knowledge about relevant infection prevention measures, considering the importance of the issue and the lack of study in the area. Methods: A total of 100 clinics that perform minimally invasive aesthetic procedures in Porto Alegre (RS), Brazil, were visited. Procedures such as botulin-toxin, dermal fillers, collagen biostimulators, thread lift, chemical peels and laser hair removal were considered. A questionnaire about infection prevention measures were answered by 50 professionals. Also, 100 samples were collected from the environment for bacterial identification and antimicrobial susceptibility testing. Results: There was an infection prevention protocol in 40% of clinics, in which 95% of respondents had complete college education. Periodic professional training regarding infection control measures were performed in 72% of clinics. An autoclave was used for sterilization of materials and instruments in 66% of clinics. From the samples collected, 85% showed bacterial growth by microbiological methods. Coagulase-negative Staphylococci was the most prevalent genera found, and 16% of them were resistant to both cefoxitin, erythromycin, and clindamycin. Four isolates were positive for mecA by PCR. Conclusion: The presence of well-trained professionals is critical in aesthetic clinics so that biosafety and infection prevention measures are taken.(AU)

Justificativa e Objetivos: Este estudo teve como objetivo identificar a presença de microrganismos no ambiente estético e avaliar o conhecimento dos profissionais sobre medidas relevantes de prevenção de infecções, considerando a importância do tema e a falta de estudos nesta área. Métodos: Foram visitadas 100 clínicas que realizam procedimentos estéticos minimamente invasivos em Porto Alegre (RS), Brasil. Foram considerados procedimentos injetáveis como aplicação de toxina botulínica, preenchedores faciais, microagulhamento, bioestimuladores de colágeno, fios de sustentação, peelings químicos e depilação a laser. Um questionário sobre medidas de prevenção de infecção foi respondido por 50 profissionais. Além disso, 100 amostras foram coletadas do ambiente para identificação bacteriana e teste de sensibilidade aos antimicrobianos. Resultados: Existia protocolo de prevenção de infecção em 40% dos ambulatórios, no qual 95% dos profissionais entrevistados possuíam ensino superior completo. Treinamento profissional periódico sobre medidas de controle de infecção foi realizado em 72% dos ambulatórios. Autoclave foi utilizada para esterilização de materiais e instrumentais em 66% das clínicas. Das amostras coletadas, 85% apresentaram crescimento bacteriano nas culturas microbiológicas. Staphylococci coagulase-negativo foi o gênero mais prevalente encontrado; e 16% deles eram resistentes à cefoxitina, eritromicina e clindamicina. Quatro isolados foram positivos para mecA por PCR. Conclusão: A presença de profissionais devidamente treinados é fundamental nas clínicas de estética, para que medidas de biossegurança e prevenção de infecções sejam tomadas.(AU)

Justificación y Objetivos: Este estudio tuvo como objetivo identificar la presencia de microorganismos en el entorno estético y evaluar el conocimiento de los profesionales sobre las medidas de prevención de infecciones relevantes, considerando la importancia del tema y la falta de estudios en esta área. Métodos: Se visitaron 100 clínicas que realizan procedimientos estéticos mínimamente invasivos en Porto Alegre (RS), Brasil. Se consideraron procedimientos invasivos, como la aplicación de toxina botulínica, rellenos faciales, microagujas, bioestimuladores de colágeno, hilos de soporte, peelings químicos y depilación láser. Un cuestionario sobre medidas de prevención de infecciones fue respondido por 50 profesionales. Además, se recolectaron 100 muestras del medio ambiente para la identificación bacteriana y las pruebas de susceptibilidad a los antimicrobianos. Resultados: Existía un protocolo de prevención de infecciones en el 40% de las clínicas, en el que el 95% de los profesionales encuestados tenía educación universitaria completa. En el 72% de las clínicas se realizó capacitación profesional periódica sobre medidas de control de infecciones. Se utilizó un autoclave para la esterilización de materiales e instrumentos en el 66% de las clínicas. De las muestras recolectadas, el 85% mostró crecimiento bacteriano por métodos de cultivo microbiologicos. El Staphylococci coagulasa negativo fue el género más prevalente encontrado, y el 16% de ellos eran resistentes tanto a cefoxitina, eritromicina y clindamicina. Cuatro aislamientos fueron positivos para mecA por PCR. Conclusión: La presencia de profesionales debidamente capacitados es fundamental en las clínicas de estética, para la toma medidas de bioseguridad y prevención de infecciones.(AU)

Emerging technologies and infection models in cellular microbiology.

The field of cellular microbiology, rooted in the co-evolution of microbes and their hosts, studies intracellular pathogens and their manipulation of host cell machinery. In this review, we highlight emerging technologies and infection models that recently promoted opportunities in cellular microbiology. We overview the explosion of microscopy techniques and how they reveal unprecedented detail at the host-pathogen interface. We discuss the incorporation of robotics and artificial intelligence to image-based screening modalities, biochemical mapping approaches, as well as dual RNA-sequencing techniques. Finally, we describe chips, organoids and animal models used to dissect biophysical and in vivo aspects of the infection process. As our knowledge of the infected cell improves, cellular microbiology holds great promise for development of anti-infective strategies with translational applications in human health.

An integrative understanding of the large metabolic shifts induced by antibiotics in critical illness.

Antibiotics are commonly used in the Intensive Care Unit (ICU); however, several studies showed that the impact of antibiotics to prevent infection, multi-organ failure, and death in the ICU is less clear than their benefit on course of infection in the absence of organ dysfunction. We characterized here the compositional and metabolic changes of the gut microbiome induced by critical illness and antibiotics in a cohort of 75 individuals in conjunction with 2,180 gut microbiome samples representing 16 different diseases. We revealed an "infection-vulnerable" gut microbiome environment present only in critically ill treated with antibiotics (ICU+). Feeding of Caenorhabditis elegans with Bifidobacterium animalis and Lactobacillus crispatus, species that expanded in ICU+ patients, revealed a significant negative impact of these microbes on host viability and developmental homeostasis. These results suggest that antibiotic administration can dramatically impact essential functional activities in the gut related to immune responses more than critical illness itself, which might explain in part untoward effects of antibiotics in the critically ill.

Enteric pathogens induce tissue tolerance and prevent neuronal loss from subsequent infections.

The enteric nervous system (ENS) controls several intestinal functions including motility and nutrient handling, which can be disrupted by infection-induced neuropathies or neuronal cell death. We investigated possible tolerance mechanisms preventing neuronal loss and disruption in gut motility after pathogen exposure. We found that following enteric infections, muscularis macrophages (MMs) acquire a tissue-protective phenotype that prevents neuronal loss, dysmotility, and maintains energy balance during subsequent challenge with unrelated pathogens. Bacteria-induced neuroprotection relied on activation of gut-projecting sympathetic neurons and signaling via ß2-adrenergic receptors (ß2AR) on MMs. In contrast, helminth-mediated neuroprotection was dependent on T cells and systemic production of interleukin (IL)-4 and IL-13 by eosinophils, which induced arginase-expressing MMs that prevented neuronal loss from an unrelated infection located in a different intestinal region. Collectively, these data suggest that distinct enteric pathogens trigger a state of disease or tissue tolerance that preserves ENS number and functionality.

A Modern-World View of Host-Microbiota-Pathogen Interactions.

The microbiota-the diverse set of commensal microbes that normally colonize humans-represents the first line of defense against infectious diseases. In this review, we summarize the direct and indirect mechanisms by which the microbiota modulates susceptibility to, and severity of, infections, with a focus on immunological mechanisms. Moreover, we highlight some of the ways that modern-world lifestyles have influenced the structure-function relationship between the microbiota and infectious diseases. Ultimately, understanding how the microbiota influences infectious risks will facilitate development of microbiota-derived therapeutics that bolster host defenses.

Antimicrobial and Antibiofilm Activity of Curcumin-Loaded Electrospun Nanofibers for the Prevention of the Biofilm-Associated Infections.

Curcumin extracted from the rhizome of Curcuma Longa has been used in therapeutic preparations for centuries in different parts of the world. However, its bioactivity is limited by chemical instability, water insolubility, low bioavailability, and extensive metabolism. In this study, the coaxial electrospinning technique was used to produce both poly (ε-caprolactone) (PCL)-curcumin and core-shell nanofibers composed of PCL and curcumin in the core and poly (lactic acid) (PLA) in the shell. Morphology and physical properties, as well as the release of curcumin were studied and compared with neat PCL, showing the formation of randomly oriented, defect-free cylindrical fibers with a narrow distribution of the dimensions. The antibacterial and antibiofilm potential, including the capacity to interfere with the quorum-sensing mechanism, was evaluated on Pseudomonas aeruginosa PAO1, and Streptococcus mutans, two opportunistic pathogenic bacteria frequently associated with infections. The reported results demonstrated the ability of the Curcumin-loading membranes to inhibit both PAO1 and S. mutans biofilm growth and activity, thus representing a promising solution for the prevention of biofilm-associated infections. Moreover, the high biocompatibility and the ability to control the oxidative stress of damaged tissue, make the synthesized membranes useful as scaffolds in tissue engineering regeneration, helping to accelerate the healing process.

Lytic Polysaccharide Monooxygenases as Chitin-Specific Virulence Factors in Crayfish Plague.

The oomycete pathogen Aphanomyces astaci, also known as "crayfish plague", is an obligate fungal-like parasite of freshwater crustaceans and is considered responsible for the ongoing decline of native European crayfish populations. A. astaci is thought to secrete a wide array of effectors and enzymes that facilitate infection, however their molecular mechanisms have been poorly characterized. Here, we report the identification of AA15 lytic polysaccharide monooxygenases (LPMOs) as a new group of secreted virulence factors in A. astaci. We show that this enzyme family has greatly expanded in A. astaci compared to all other oomycetes, and that it may facilitate infection through oxidative degradation of crystalline chitin, the most abundant polysaccharide found in the crustacean exoskeleton. These findings reveal new roles for LPMOs in animal-pathogen interactions, and could help inform future strategies for the protection of farmed and endangered species.

Sample size calculation for phylogenetic case linkage.

Sample size calculations are an essential component of the design and evaluation of scientific studies. However, there is a lack of clear guidance for determining the sample size needed for phylogenetic studies, which are becoming an essential part of studying pathogen transmission. We introduce a statistical framework for determining the number of true infector-infectee transmission pairs identified by a phylogenetic study, given the size and population coverage of that study. We then show how characteristics of the criteria used to determine linkage and aspects of the study design can influence our ability to correctly identify transmission links, in sometimes counterintuitive ways. We test the overall approach using outbreak simulations and provide guidance for calculating the sensitivity and specificity of the linkage criteria, the key inputs to our approach. The framework is freely available as the R package phylosamp, and is broadly applicable to designing and evaluating a wide array of pathogen phylogenetic studies.