The soil microbiota exhibits an important function in the ecosystem, and its response to climate change is of paramount importance for sustainable agroecosystems. The macronutrients, micronutrients, and additional constituents vital for the growth of plants are cycled biogeochemically under the regulation of the soil microbiome. Identifying and forecasting the effect of climate change on soil microbiomes and ecosystem services is the need of the hour to address one of the biggest global challenges of the present time. The impact of climate change on the structure and function of the soil microbiota is a major concern, explained by one or more sustainability factors around resilience, reluctance, and rework. However, the past research has revealed that microbial interventions have the potential to regenerate soils and improve crop resilience to climate change factors. The methods used therein include using soil microbes' innate capacity for carbon sequestration, rhizomediation, bio-fertilization, enzyme-mediated breakdown, phyto-stimulation, biocontrol of plant pathogens, antibiosis, inducing the antioxidative defense pathways, induced systemic resistance response (ISR), and releasing volatile organic compounds (VOCs) in the host plant. Microbial phytohormones have a major role in altering root shape in response to exposure to drought, salt, severe temperatures, and heavy metal toxicity and also have an impact on the metabolism of endogenous growth regulators in plant tissue. However, shelf life due to the short lifespan and storage time of microbial formulations is still a major challenge, and efforts should be made to evaluate their effectiveness in crop growth based on climate change. This review focuses on the influence of climate change on soil physico-chemical status, climate change adaptation by the soil microbiome, and its future implications.
Corynebacterium (C.) durum je součástí rezidentní flóry dutiny ústní. Jeho podíl na etiologii infekčních onemocnění je nejednoznačný. S vyšším počtem imunoalterovaných pacientů je nutné s ním počítat jako s potenciálním oportunním patogenem. Nejčastěji je izolováno ze sputa, bronchoalveolární lavážní tekutiny, ale také z krve, zejména u imunosuprimovaných pacientů s pneumonií. V tom případě je nutné bakterii přesně identifikovat a nález správně interpretovat. Dříve velmi využívaný komerční test pro určení korynebakterií (API Coryne, BioMerieux) nelze použít pro všechna korynebakteria včetně C. durum. Tento druh není obsažen v databázi biotypových čísel. Lze provést porovnání biotypového čísla s údaji v literatuře. K přesnému odlišení od jiných korynebakterií je nutná chemotaxonomická a proteomická analýzy (MALDI-TOF MS), nebo sekvenace genu 16S rRNA. Klíčový je polyfázový přístup využívající poznatky z jednotlivých laboratorních vyšetření.
Corynebaterium (C.) durum is a part of the resident human oral microbiota. Its role in the aetiology of infectious diseases is ambiguous. With the increasing number of immunocompromised patients, it must be considered a potential opportunistic pathogen. It is isolated from the sputum, bronchoalveolar-lavage fluid, as well as blood, especially from immunocompromised patients with pneumonia. In that case, the critical steps involve a correct identification of Corynebacterium to the species level and right interpretation of the findings. The previously widely used commercial test for the identification of Corynebacteria (API Coryne, BioMerieux) is not suitable for all species, including C. durum, as its biotype number is not included in the database. But the obtained result can be compared with the available literature data. Chemotaxonomic and proteomic analysis (matrix-assisted laser desorption/ ionization – time of flight, MALDI-TOF MS) or 16S rRNA sequencing allow for accurate differentiation from the other Corynebacteria species. Nevertheless, these methods are not routinely used in clinical laboratories. A polyphasic approach to the taxonomy based on the data from combined laboratory tests is crucial.
- MeSH
- Bronchoalveolar Lavage Fluid microbiology MeSH
- Corynebacterium * isolation & purification MeSH
- Immunocompromised Host MeSH
- Corynebacterium Infections diagnosis MeSH
- Blood microbiology MeSH
- Humans MeSH
- Microbiological Techniques methods MeSH
- Opportunistic Infections microbiology MeSH
- RNA, Ribosomal, 16S genetics MeSH
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods MeSH
- Sputum microbiology MeSH
- Check Tag
- Humans MeSH
BACKGROUND: Tick-borne encephalitis virus (TBEV) is a significant threat to human health. The virus causes potentially fatal disease of the central nervous system (CNS), for which no treatments are available. TBEV infected individuals display a wide spectrum of neuronal disease, the determinants of which are undefined. Changes to host metabolism and virus-induced immunity have been postulated to contribute to the neuronal damage observed in infected individuals. In this study, we evaluated the cytokine, chemokine, and metabolic alterations in the cerebrospinal fluid (CSF) of symptomatic patients infected with TBEV presenting with meningitis or encephalitis. Our aim was to investigate the host immune and metabolic responses associated with specific TBEV infectious outcomes. METHODS: CSF samples of patients with meningitis (n = 27) or encephalitis (n = 25) were obtained upon consent from individuals hospitalised with confirmed TBEV infection in Brno. CSF from uninfected control patients was also collected for comparison (n = 12). A multiplex bead-based system was used to measure the levels of pro-inflammatory cytokines and chemokines. Untargeted metabolomics followed by bioinformatics and integrative omics were used to profile the levels of metabolites in the CSF. Human motor neurons (hMNs) were differentiated from induced pluripotent stem cells (iPSCs) and infected with the highly pathogenic TBEV-Hypr strain to profile the role(s) of identified metabolites during the virus lifecycle. Virus infection was quantified via plaque assay. RESULTS: Significant differences in proinflammatory cytokines (IFN-α2, TSLP, IL-1α, IL-1β, GM-CSF, IL-12p40, IL-15, and IL-18) and chemokines (IL-8, CCL20, and CXCL11) were detected between neurological-TBEV and control patients. A total of 32 CSF metabolites differed in TBE patients with meningitis and encephalitis. CSF S-Adenosylmethionine (SAM), Fructose 1,6-bisphosphate (FBP1) and Phosphoenolpyruvic acid (PEP) levels were 2.4-fold (range ≥ 2.3-≥3.2) higher in encephalitis patients compared to the meningitis group. CSF urocanic acid levels were significantly lower in patients with encephalitis compared to those with meningitis (p = 0.012209). Follow-up analyses showed fluctuations in the levels of O-phosphoethanolamine, succinic acid, and L-proline in the encephalitis group, and pyruvic acid in the meningitis group. TBEV-infection of hMNs increased the production of SAM, FBP1 and PEP in a time-dependent manner. Depletion of the metabolites with characterised pharmacological inhibitors led to a concentration-dependent attenuation of virus growth, validating the identified changes as key mediators of TBEV infection. CONCLUSIONS: Our findings reveal that the neurological disease outcome of TBEV infection is associated with specific and dynamic metabolic signatures in the cerebrospinal fluid. We describe a new in vitro model for in-depth studies of TBEV-induced neuropathogenesis, in which the depletion of identified metabolites limits virus infection. Collectively, this reveals new biomarkers that can differentiate and predict TBEV-associated neurological disease. Additionally, we have identified novel therapeutic targets with the potential to significantly improve patient outcomes and deepen our understanding of TBEV pathogenesis.
- MeSH
- Cytokines cerebrospinal fluid MeSH
- Adult MeSH
- Encephalitis, Tick-Borne * cerebrospinal fluid metabolism MeSH
- Cells, Cultured MeSH
- Middle Aged MeSH
- Humans MeSH
- Metabolome * physiology MeSH
- Metabolomics MeSH
- Young Adult MeSH
- Neurons * metabolism virology MeSH
- Aged MeSH
- Encephalitis Viruses, Tick-Borne * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Escherichia coli (E. coli) is a rod-shaped gram-negative bacterium that includes the diarrheagenic strains, an identical group of intestinal pathogens.E. coli diarrhea is transmitted through the feco-oral route, through contaminated food and water. Enteropathogenic E. coli (EPEC) is one of the leading causes of diarrhea in the pediatric age group in developing and developed countries. Depending on the absence or presence of E. coli adherence factor plasmids, they are classified as typical or atypical isolates. The distinguishing feature of EPEC's pathology is the attaching and effacing lesions, which facilitate localized damage by tightly adhering to intestinal epithelial cells, disarranging their surfaces, and effacing microvilli. Typical EPEC possess the locus of enterocyte effacement (LEE), a pathogenicity island, encoding adherence factors, including the Type III Secretion System (T3SS), a needle-like structure injecting effector proteins into host cells. EPEC also have other effector genes like cif or nleC encoded by non-LEE pathogenicity islands, which enable destruction of tight junctions in the host cell. Another key virulence factor is bundle-forming pili (BFP), which aids in the first attachment to enterocytes. Methods like quantitative PCR exist to diagnose EPEC accurately. As of today, no licensed vaccine exists to prevent EPEC infections. Virulence factors for attachment, such as bfpA and intimin, and immunogenic carriers can be potential candidates for vaccine development. Moreover, studies are required to better understand the interaction of EPECwith the intestinal microbiome and immune evasion strategies. This article is aimed at providing a comprehensive review of the epidemiology, transmission, virulence factors, challenges in studying EPEC virulence factors, pathogenesis, host-pathogen interaction, mechanism of intestinal injury, diagnosis, treatment, antibiotic resistance, and vaccination strategy for EPEC, and future research implications. We conducted a comprehensive literature search using credible sources such as PubMed, Google Scholar, and Scopus. We refined our keywords, applied database filters, and assessed citations in the included studies. No meta-analysis, statistical aggregation, or formal evaluation of risk bias was carried out as this review consolidates the literature narratively. High-quality English articles published in reputable peer-reviewed journals from 2010 to 2025 were analyzed, and their findings have been summarized in this comprehensive review.
- Publication type
- Journal Article MeSH
- Review MeSH
Macrocyclic inhibitors have emerged as a privileged scaffold in medicinal chemistry, offering enhanced selectivity, stability, and pharmacokinetic profiles compared to their linear counterparts. Here, we describe a novel, on-resin macrocyclization strategy for the synthesis of potent inhibitors targeting the secreted protease Major Aspartyl Peptidase 1 in Cryptococcus neoformans, a pathogen responsible for life-threatening fungal infections. By employing diverse aliphatic linkers and statine-based transition-state mimics, we constructed a focused library of 624 macrocyclic compounds. Screening identified several subnanomolar inhibitors with desirable pharmacokinetic and antifungal properties. Lead compound 25 exhibited a Ki of 180 pM, significant selectivity against host proteases, and potent antifungal activity in culture. The streamlined synthetic approach not only yielded drug-like macrocycles with potential in antifungal therapy but also provided insights into structure-activity relationships that can inform broader applications of macrocyclization in drug discovery.
- MeSH
- Antifungal Agents * pharmacology chemistry chemical synthesis pharmacokinetics MeSH
- Cryptococcus neoformans * drug effects enzymology MeSH
- Protease Inhibitors * pharmacology chemistry chemical synthesis pharmacokinetics MeSH
- Humans MeSH
- Macrocyclic Compounds * pharmacology chemistry chemical synthesis pharmacokinetics MeSH
- Microbial Sensitivity Tests MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
UNLABELLED: We investigated the tripartite interactions between two intracellular bacterial symbionts, Cardinium and Wolbachia in Tyrophagus putrescentiae. Cultures of Tyrophagus putrescentiae are typically single-infected by one intracellular symbiont. However, co-infection can be experimentally induced by mixing single-infected cultures, resulting in 10% of mite individuals being double-infected (Cardinium + Wolbachia) and a corresponding reduction in host fitness. Here, we assembled the genomes of Cardinium and Wolbachia and analyzed their gene expression in parental single-infected and mixed mite cultures using population-level samples (ranging from 7,500 to 10,000 mites). Wolbachia interacts more extensively with its mite host than Cardinium in single-infected cultures. However, in mixed cultures, (i) Wolbachia exhibited reduced regulation of the host compared with Cardinium; (ii) the gene expression profile of Cardinium shifted, increasing its interactions with the host, whereas the gene expression profile of Wolbachia remained unchanged; and (iii) Wolbachia genes exhibited a loss of interactions with mite gene expression, as indicated by reduced correlations (for example with host MAPK, endocytosis, and calcium signaling pathways). The experiments show that at the mite population level, symbiont infection disrupts gene expression interaction between the two symbionts and their host in different ways. Wolbachia was more influenced by Cardinium gene expression than vice versa. Cardinium can inhibit the growth of Wolbachia by disrupting its interaction with the host, leading to a loss of Wolbachia's influence on mite immune and regulatory pathways. The reasons for responses are due to co-infection or the reduced frequency of Wolbachia single-infected individuals due to the analyses of population-level samples. IMPORTANCE: We found that Cardinium disrupts the interaction between Wolbachia and mite host. In Wolbachia single-infected cultures, strong correlations exist between symbiont and host gene expressions. Interestingly, although Cardinium can also interact with the host, this interaction appears weaker compared with Wolbachia in single-infected cultures. These results suggest that both symbionts affect mite host gene expression, particularly in immune and regulatory pathways. In mixed samples, Cardinium appears to outcompete Wolbachia by disrupting its host interaction. It indicates competition between these two intracellular symbionts in mite populations. Wolbachia belongs to a mite-specific supergroup Q, distinct from the more commonly studied Wolbachia supergroups. As these mite-specific bacteria exhibit pathogen-blocking effects, our findings may have relevance for other systems, such as ticks and tick-borne diseases. The study sheds light on intracellular symbiont interaction within a novel mite-symbiont model.
- MeSH
- Bacteroidetes * physiology genetics MeSH
- Mites * microbiology MeSH
- Symbiosis MeSH
- Wolbachia * genetics physiology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
The parasitic protozoan Entamoeba histolytica secretes extracellular vesicles (EVs), but so far little is known about their function in the interaction with the host immune system. Infection with E. histolytica trophozoites can lead to formation of amebic liver abscesses (ALAs), in which pro-inflammatory immune responses of Ly6Chi monocytes contribute to liver damage. Men exhibit a more severe pathology as the result of higher monocyte recruitment and a stronger immune response. To investigate the role of EVs and pathogenicity in the host immune response, we studied the effect of EVs secreted by low pathogenic EhA1 and highly pathogenic EhB2 amebae on monocytes. Size and quantity of isolated EVs from both clones were similar. However, they differed in their proteome and miRNA cargo, providing insight into factors potentially involved in amebic pathogenicity. In addition, EVs were enriched in proteins with signaling peptides compared with the total protein content of trophozoites. Exposure to EVs from both clones induced monocyte activation and a pro-inflammatory immune response as evidenced by increased surface presentation of the activation marker CD38 and upregulated gene expression of key signaling pathways (including NF-κB, IL-17 and TNF signaling). The release of pro-inflammatory cytokines was increased in EV-stimulated monocytes and more so in male- than in female-derived cells. While EhA1 EV stimulation caused elevated myeloperoxidase (MPO) release by both monocytes and neutrophils, EhB2 EV stimulation did not, indicating the protective role of MPO during amebiasis. Collectively, our results suggest that parasite-released EVs contribute to the male-biased immunopathology mediated by pro-inflammatory monocytes during ALA formation.
- MeSH
- Liver Abscess, Amebic immunology parasitology MeSH
- Cytokines metabolism MeSH
- Entamoebiasis immunology parasitology MeSH
- Entamoeba histolytica * immunology pathogenicity genetics MeSH
- Extracellular Vesicles * immunology metabolism MeSH
- Humans MeSH
- Monocytes * immunology parasitology MeSH
- Signal Transduction * MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Klebsiella pneumoniae, a Gram-negative bacterium, comprises strains with diverse virulence potentials, ranging from classical to hypervirulent variants. Understanding the genetic basis underlying the virulence disparities between hypervirulent (hvKp) and classical K. pneumoniae (cKp) strains is crucial. hvKp strains are characterized by hypermucoviscosity, attributed to the presence of specific virulence genes and the production of molecules that aid in their ability to survive, evade host immune defenses, and cause infection. In contrast, classical strains exhibit a broader array of antimicrobial resistance determinants, conferring resistance to multiple antibiotics. Although current definitions of hvKp incorporate clinical features, phenotypes, and genotypes, identifying hvKp strains in clinical settings remains challenging. Genomic studies have been pivotal and have helped to identify distinct genetic profiles in hvKp strains, including unique virulence plasmids and chromosomal variations, underscoring the genetic diversity within K. pneumoniae populations. This review examines the virulence and genetic determinants associated with hvKp. The presence of genes defining hypervirulence, alongside considerations of their utility as biomarkers and targets for therapeutic strategies, is discussed, while also providing insight into biofilm formation by hvKp and key questions that need urgent responses in understanding hvKp.
- MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Biofilms growth & development MeSH
- Virulence Factors * genetics MeSH
- Klebsiella Infections * microbiology MeSH
- Klebsiella pneumoniae * pathogenicity genetics drug effects MeSH
- Humans MeSH
- Virulence genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Super- and low-shedding phenomena have been observed in genetically homogeneous hosts infected by a single bacterial strain. To decipher the mechanisms underlying these phenotypes, we conducted an experiment with chicks infected with Salmonella Enteritidis in a non-sterile isolator, which prevents bacterial transmission between animals while allowing the development of the gut microbiota. We investigated the impact of four commensal bacteria called Mix4, inoculated at hatching, on chicken systemic immune response and intestinal microbiota composition and functions, before and after Salmonella infection. Our results revealed that these phenotypes were not linked to changes in cell invasion capacity of bacteria during infection. Mix4 inoculation had both short- and long-term effects on immune response and microbiota and promoted the low-shedder phenotype. Kinetic analysis revealed that Mix4 activated immune response from day 4, which modified the microbiota on day 6. This change promotes a more fermentative microbiota, using the aromatic compounds degradation pathway, which inhibited Salmonella colonization by day 11 and beyond. In contrast, control animals exhibited a delayed TNF-driven pro-inflammatory response and developed a microbiota using anaerobic respiration, which facilitates Salmonella colonization and growth. This strategy offers promising opportunities to strengthen the barrier effect against Salmonella and possibly other pathogens.
- MeSH
- Bacteria * classification genetics isolation & purification MeSH
- Chickens * microbiology immunology MeSH
- Poultry Diseases * microbiology immunology prevention & control MeSH
- Salmonella enteritidis * immunology growth & development MeSH
- Salmonella Infections, Animal * microbiology immunology prevention & control MeSH
- Gastrointestinal Microbiome * MeSH
- Symbiosis MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
The rising burden of fungal infections presents a significant challenge to global healthcare, particularly with increasing antifungal resistance limiting treatment efficacy. Early detection and timely intervention remain critical, yet fungal pathogens employ diverse mechanisms to evade host immunity and develop resistance, undermining existing therapeutic options. Limited antifungal options and rising resistance necessitate novel treatment strategies. This review provides a comprehensive overview of conventional antifungal agents, their mechanisms of action, and emerging resistance pathways. Furthermore, it highlights recently approved and investigational antifungal compounds while evaluating innovative approaches such as nanotechnology, drug repurposing, and immunotherapy. Addressing antifungal resistance requires a multifaceted strategy that integrates novel therapeutics, enhanced diagnostic tools, and future research efforts to develop sustainable and effective treatment solutions.
- Publication type
- Journal Article MeSH
- Review MeSH
