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Aspergillosis is a fungal infection caused by various species of Aspergillus, most notably A. fumigatus. This fungus causes a spectrum of diseases, including allergic bronchopulmonary aspergillosis, aspergilloma, chronic pulmonary aspergillosis, and invasive aspergillosis. The clinical manifestations and severity of aspergillosis can vary depending on individual immune status and the specific species of Aspergillus involved. The recognition of Aspergillus involves pathogen-associated molecular patterns (PAMPs) such as glucan, galactomannan, mannose, and conidial surface proteins. These are recognized by the pathogen recognition receptors present on immune cells such as Toll-like receptors (TLR-1,2,3,4, etc.) and C-type lectins (Dectin-1 and Dectin-2). We discuss the roles of cytokines and pathogen recognition in aspergillosis from both the perspective of human and experimental infection. Several cytokines and chemokines have been implicated in the immune response to Aspergillus infection, including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), CCR4, CCR17, and other interleukins. For example, allergic bronchopulmonary aspergillosis (ABPA) is characterized by Th2 and Th9 cell-type immunity and involves interleukin (IL)-4, IL-5, IL-13, and IL-10. In contrast, it has been observed that invasive aspergillosis involves Th1 and Th17 cell-type immunity via IFN-γ, IL-1, IL-6, and IL-17. These cytokines activate various immune cells and stimulate the production of other immune molecules, such as antimicrobial peptides and reactive oxygen species, which aid in the clearance of the fungal pathogen. Moreover, they help to initiate and coordinate the immune response, recruit immune cells to the site of infection, and promote clearance of the fungus. Insight into the host response from both human and animal studies may aid in understanding the immune response in aspergillosis, possibly leading to harnessing the power of cytokines or cytokine (receptor) antagonists and transforming them into precise immunotherapeutic strategies. This could advance personalized medicine. [ABSTRACT FROM AUTHOR]

This article, titled "Editorial: Rhizospheric interactions: integrating plant-microbe signaling during stresses," explores the importance of understanding plant interactions and their impact on the ecosystem, particularly in the context of agricultural practices. The article emphasizes the need for eco-friendly and sustainable approaches to agriculture, highlighting the role of rhizospheric interactions in nutrient acquisition, stress resistance, and overall plant growth. It discusses the various ways in which rhizospheric microbes contribute to plant health and defense mechanisms, as well as the potential for these interactions to be utilized in sustainable agricultural practices. The article also mentions specific studies that have investigated the role of rhizospheric interactions in plant stress resistance and growth promotion. [Extracted from the article]

The discovery of antibiotics has fully changed medicinal therapy. However, with the increased therapeutic use of antibiotics, bacteria continued to develop mechanisms to resist these drugs. Today, antibiotics are being prescribed to a range of patients from the common cold to cancer. Antibiotics are poorly metabolized in the body, about 70–80% of them are excreted out. The imprudent and exceeding use of clinically significant antibiotics in agriculture, veterinary medicine, and human healthcare is a causative factor in the escalating global antimicrobial resistance (AMR) epidemic. Researchers and stakeholders are increasingly expressing concern regarding the environment playing a role as a reservoir for AMR and its significant contribution to the dissemination of antimicrobial resistance genes. Multiple drivers contribute to the dissemination of antibiotic-resistant bacteria (ARB) and their associated antibiotic-resistance genes (ARGs). These drivers include direct factors, e.g., the usage of antimicrobial drugs in healthcare, agriculture, livestock, and the environment. The release of antibiotic residues from various domestic settings also contributes to this phenomenon. The main focus of global mitigation strategies is to identify environments that pose a high risk of resistance development and dissemination. The transmission of AMR is subsequently influenced by various factors, including infection control standards, sanitation practices, availability of clean water, access to reliable antimicrobials and diagnostics, and treatment of agriculture and hospital waste. Therefore, we aim to present the global problem of environmental antibiotic resistance and its dissemination in the environment. The key hotspots of ARB and ARGs and their dissemination from the environment to humans are discussed. Further, we aim to highlight the mechanisms of acquiring antibiotic resistance by the environmental bacteria population and possible approaches to combat antibiotic resistance. [ABSTRACT FROM AUTHOR]

Aspergillus species are the major cause of health concern worldwide in immunocompromised individuals. Opportunistic Aspergilli cause invasive to allergic aspergillosis, whereas non-infectious Aspergilli have contributed to understand the biology of eukaryotic organisms and serve as a model organism. Morphotypes of Aspergilli such as conidia or mycelia/hyphae helped them to survive in favorable or unfavorable environmental conditions. These morphotypes contribute to virulence, pathogenicity and invasion into hosts by excreting proteins, enzymes or toxins. Morphological transition of Aspergillus species has been a critical step to infect host or to colonize on food products. Thus, we reviewed proteins from Aspergilli to understand the biological processes, biochemical, and cellular pathways that are involved in transition and morphogenesis. We majorly analyzed proteomic studies on A. fumigatus, A. flavus, A. terreus, and A. niger to gain insight into mechanisms involved in the transition from conidia to mycelia along with the role of secondary metabolites. Proteome analysis of morphotypes of Aspergilli provided information on key biological pathways required to exit conidial dormancy, consortia of virulent factors and mycotoxins during the transition. The application of proteomic approaches has uncovered the biological processes during development as well as intermediates of secondary metabolite biosynthesis pathway. We listed key proteins/ enzymes or toxins at different morphological types of Aspergillus that could be applicable in discovery of novel therapeutic targets or metabolite based diagnostic markers. [ABSTRACT FROM AUTHOR]

Aspergillus terreus is an emerging opportunistic fungal pathogen that causes invasive aspergillosis in immunocompromised individuals. The main risk group of individuals for this organism is leukopenic patients, individuals having cancers, bone marrow transplant persons and those who have immunological disorders. The lack of early diagnostic marker for A. terreus and intrinsic resistance to Amphotericin B, further limits the successful therapy of A. terreus-associated infections. The germination of inhaled conidia is the key step to establish successful invasion in host tissues or organs. Thus, profiling of expressed proteins during germination of conidia not only shed light on proteins that are involved in invasion or virulence but may also provide early diagnostic markers. We used nanoLC-Q-TOF to study the proteome of germinating conidia (at 16 h time points) of A. terreus. We observed expression of 373 proteins in germinating conidia of A. terreus. A total of 74 proteins were uncharacterized in the database. The expressed proteins were associated with various processes like cell wall modulation, virulence factors and secondary metabolite biosynthesis. The most abundant proteins were associated with protein biosynthesis, carbohydrate metabolism and unknown functions. Among virulent proteins, mitogen-activated protein kinase (hog1) and mitogen-activated protein kinase (mpkC) are key virulent proteins observed in our study. We observed 7 enzymes from terretonin and 10 enzymes from geodin mycotoxin biosynthesis pathway. Interestingly, we observed expression of terrelysin protein, associated with blood cell lysis. Quantitative RT-PCR analysis showed 26-fold increase in transcripts encoding for dihydrogeodin oxidase and 885-fold for terrelysin gene in germinating conidia in comparison to conidia. Further, we propose that terrelysin protein and secondary metabolite such as geodin could be explored as diagnostic marker for A. terreus-associated infections. [ABSTRACT FROM AUTHOR]

Aspergillus flavus is the second most leading cause of aspergillosis. The ability of A. flavus to adapt within the host environment is crtical for its colonization. Onset of germination of conidia is one of the crucial events; thus, in order to gain insight into A. flavus molecular adaptation while germination, protein profile of A. flavus was obtained. Approximately 82 % of conidia showed germination at 7 h; thus, samples were collected followed by protein extraction and subjected to nLC-Q-TOF mass spectrometer. Q-TOF data were analysed using Protein Lynx Global Services (PLGS 2.2.5) software. A total of 416 proteins were identified from UniProt Aspergillus species database. Orthologues of A. flavus was observed in A. fumigatus, A. niger, A. terreus, A. oryzae, etc. Proteins were further analysed in NCBI database, which showed that 27 proteins of A. flavus are not reported in UniProt and NCBI database. Functional characterization of proteins resulted majorly to cell wall synthesis and degradation, metabolisms (carbohydrate and amino acid metabolism), protein synthesis and degradation. Proteins/enzymes associated with aflatoxin biosynthesis were observed. We also observed Dicer-like proteins 1, 2 and autophagy-related proteins 2, 9, 18, 13, 11, 22. Expression of protein/enzymes associated with MAPK signalling pathway suggests their role during the germination process. Overall, the data present a catalogue of proteins/enzymes involved in the germination of A. flavus conidia and could also be applied to other Aspergillus species. [ABSTRACT FROM AUTHOR]

Pentraxin-3 (PTX-3) protein is an evolutionary conserved protein that acts as a soluble pattern-recognition receptor for pathogens and plays important role in innate immune response. It recognizes various pathogens by interacting with extracellular moieties such as glactomannan of conidia (Aspergillus fumigatus), lipopolysaccharide of Pseudomonas aeruginosa, Streptococcus pneumonia and Salmonella typhimurium. Thus, PTX-3 protein helps to clear these pathogens by activating downstream innate immune process. In this study, computational methods were used to analyze various non-synonymous single nucleotide polymorphisms (nsSNPs) in PTX-3 gene. Three different databases were used to retrieve SNP data sets followed by seven different in silico algorithms to screen nsSNPs in PTX-3 gene. Sequence homology based approach was used to identify nsSNPs. Conservation profile of PTX-3 protein amino acid residues were predicted by ConSurf web server. In total, 10 high-risk nsSNPs were identified in pentraxin-domain of PTX-3 gene. Out of these 10 high-risk nsSNPs, 4 were present in the conserved structural and functional residues of the pentraxin-domain, hence, selected for structural analyses. The results showed alteration in the putative structure of pentraxin-domain. Prediction of protein-protein interactions analysis showed association of PTX-3 protein with C1q component of complement pathway. Different functional and structural residues along with various putative phosphorylation sites and evolutionary relationship were also predicted for PTX-3 protein. This is the first extensive computational analyses of pentraxin protein family with nsSNPs and will serve as a valuable resource for future population based studies. [ABSTRACT FROM AUTHOR]

Stress (biotic or abiotic) is an unfavourable condition for an organism including fungus. To overcome stress, organism expresses heat-shock proteins (Hsps) or chaperons to perform biological function. Hsps are involved in various routine biological processes such as transcription, translation and posttranslational modifications, protein folding, and aggregation and disaggregation of proteins. Thus, it is important to understand holistic role of Hsps in response to stress and other biological conditions in fungi. Hsp104, Hsp70, and Hsp40 are found predominant in replication and Hsp90 is found in transcriptional and posttranscriptional process. Hsp90 and Hsp70 in combination or alone play a major role in morphogenesis and dimorphism. Heat stress in fungi expresses Hsp60, Hsp90, Hsp104, Hsp30, and Hsp10 proteins, whereas expression of Hsp12 protein was observed in response to cold stress. Hsp30, Hsp70, and Hsp90 proteins showed expression in response to pH stress. Osmotic stress is controlled by small heat-shock proteins and Hsp60. Expression of Hsp104 is observed under high pressure conditions. Out of these heat-shock proteins, Hsp90 has been predicted as a potential antifungal target due to its role in morphogenesis. Thus, current review focuses on role of Hsps in fungi during morphogenesis and various stress conditions (temperature, pH, and osmotic pressure) and in antifungal drug tolerance. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis caused by Aspergillus species (Aspergillus fumigatus, A. flavus, and A. terreus) is life-threatening infections in immunocompromised patients. Understanding the innate and adaptive immune response particularly T-helper cells (TH-cells) against these Aspergillus species and how the different sub-set of TH-cells are regulated by differentiating cytokines at primary target organ site like lung, kidney and brain is of great significance to human health. This review focuses on presentation of Aspergillus through Antigen presenting cells (APCs) to the naive CD4+ T-cells in the host. The production of differentiating/effector cytokines that activate following TH-cells, e.g., TH1, TH2, TH9, and TH17 has been reported in association or alone in allergic or invasive aspergillosis. Chemokines (CXCL1, CXCL2, CCL1, and CCL20) and their receptors associated to these TH-cells have also been observed in invasive aspergillosis. Thus, further study of these TH-cells in invasive aspergillosis and other elements of adaptive immune response with Aspergillus species are required in order to have a better understanding of host response for safer and effective therapeutic outcome. [ABSTRACT FROM AUTHOR]

Implant-related hypersensitivity is a well-established cause of failure after total hip arthroplasty but is a rare complication after total knee arthroplasty (TKA). It remains a relatively unpredictable and poorly understood cause of implant-related failure. This article describes 5 patients (6 knees) who presented with persistent pain and hypertrophic synovitis after TKA using a cobalt-chromium component. Extensive perioperative workup, including white blood cell count, erythrocyte sedimentation rate, C-reactive protein, joint aspiration, and intraoperative cultures, ruled out infection as a cause of the symptoms. All knees demonstrated appropriate ligamentous balance and were well aligned, with all components noted to be well fixed at revision. In all patients, the clinical condition improved dramatically after revision to zirconium femoral and titanium metal-backed tibial components. Pain and functional outcome scores improved in all patients. Intraoperative histopathology revealed a thickened synovium with either a predominantly lymphocytic or histiocytic monocellular response. Final pathology confirmed that no infection was present in any patient. The goal of TKA is to produce a well-performing, pain-free joint. When patients present with recurrent pain and synovitis after TKA, infection must be excluded. When infection and instability have been excluded, metal hypersensitivity should be considered as a cause of primary TKA failure. In these patients, revision to a zirconium femoral component can provide predictable and effective clinical improvement. [ABSTRACT FROM AUTHOR]

We present a case of pathological fracture of olecranon through a giant geode. Fracture was initially undisplaced and was treated conservatively. It later progressed to a transolecranon dislocation as a result of a pseudarthrosis at the fracture site. The patient presented 4 years later when she developed symptoms of ulnar nerve palsy. She was treated by a total elbow arthroplasty with ulnar nerve transposition. The current report highlights this unusual case and reviews the relevant literature. [ABSTRACT FROM AUTHOR]

Implant-related hypersensitivity is a well-established cause of failure after total hip arthroplasty but is a rare complication after total knee arthroplasty (TKA). It remains a relatively unpredictable and poorly understood cause of implant-related failure. This article describes 5 patients (6 knees) who presented with persistent pain and hypertrophic synovitis after TKA using a cobalt-chromium component. Extensive perioperative workup, including white blood cell count, erythrocyte sedimentation rate, C-reactive protein, joint aspiration, and intraoperative cultures, ruled out infection as a cause of the symptoms. All knees demonstrated appropriate ligamentous balance and were well aligned, with all components noted to be well fixed at revision. In all patients, the clinical condition improved dramatically after revision to zirconium femoral and titanium metal-backed tibial components. Pain and functional outcome scores improved in all patients. Intraoperative histopathology revealed a thickened synovium with either a predominantly lymphocytic or histiocytic monocellular response. Final pathology confirmed that no infection was present in any patient. The goal of TKA is to produce a well-performing, pain-free joint. When patients present with recurrent pain and synovitis after TKA, infection must be excluded. When infection and instability have been excluded, metal hypersensitivity should be considered as a cause of primary TKA failure. In these patients, revision to a zirconium femoral component can provide predictable and effective clinical improvement. [ABSTRACT FROM AUTHOR]