scholarly journals New insights into the pathogenesis of leprosy: contribution of subversion of host cell metabolism to bacterial persistence, disease progression, and transmission

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 70 ◽  
Author(s):  
Cristiana Santos de Macedo ◽  
Flavio Alves Lara ◽  
Roberta Olmo Pinheiro ◽  
Veronica Schmitz ◽  
Marcia de Berrêdo-Pinho ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Immune Responses ◽  
Schwann Cells ◽  
Immune Modulation ◽  
Fatty Acid Biosynthesis ◽  
Cell Metabolism ◽  
Clinical Signs ◽  
Metabolic Changes ◽  
Host Cells ◽  
Lipid Mediator

Chronic infection by the obligate intracellular pathogen Mycobacterium leprae may lead to the development of leprosy. Of note, in the lepromatous clinical form of the disease, failure of the immune system to constrain infection allows the pathogen to reproduce to very high numbers with minimal clinical signs, favoring transmission. The bacillus can modulate cellular metabolism to support its survival, and these changes directly influence immune responses, leading to host tolerance, permanent disease, and dissemination. Among the metabolic changes, upregulation of cholesterol, phospholipids, and fatty acid biosynthesis is particularly important, as it leads to lipid accumulation in the host cells (macrophages and Schwann cells) in the form of lipid droplets, which are sites of polyunsaturated fatty acid–derived lipid mediator biosynthesis that modulate the inflammatory and immune responses. In Schwann cells, energy metabolism is also subverted to support a lipogenic environment. Furthermore, effects on tryptophan and iron metabolisms favor pathogen survival with moderate tissue damage. This review discusses the implications of metabolic changes on the course of M. leprae infection and host immune response and emphasizes the induction of regulatory T cells, which may play a pivotal role in immune modulation in leprosy.

scholarly journals Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques

2021 ◽  
Author(s):  
Emily Speranza ◽  
Jyothi N. Purushotham ◽  
Julia R. Port ◽  
Benjamin Schwarz ◽  
Meaghan Flagg ◽  
...  
Keyword(s):  
Immune Responses ◽  
Inflammatory Responses ◽  
Rhesus Macaques ◽  
Acute Infection ◽  
Clinical Signs ◽  
Multiparameter Flow Cytometry ◽  
Lipid Mediator ◽  
Age Cohorts ◽  
Cytokine Detection ◽  
Age Related

AbstractAdvanced age is a key predictor of severe COVID-19. To gain insight into this relationship, particularly with respect to immune responses, we utilized the rhesus macaque model of SARS-CoV-2 infection. Two cohorts of eight older (16-23 years) and eight younger (3-5 years) rhesus macaques were inoculated with SARS-CoV-2. Animals were evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, and lipidomics analysis at pre-defined timepoints in various tissues. Differences in clinical signs, pulmonary infiltrates, and virus replication dynamics were limited between age cohorts. Transcriptional signatures of inflammation-associated genes in cells isolated from bronchoalveolar lavage fluid at 3 dpi revealed efficient mounting of innate immune defenses in both younger and older animals. These findings suggested that age did not substantially skew major facets of acute disease in this model. However, age-specific divergence of immune responses emerged during the post-acute phase of infection (7-21 dpi). Older animals exhibited sustained local inflammatory innate responses while local effector T-cell responses were induced earlier in the younger animals. Circulating lipid mediator and cytokine levels highlighted increased repair-associated signals in the younger animals, in contrast to persistent pro-inflammatory responses in the older animals. In summary, despite similar disease outcomes, multi-omics profiling in SARS-CoV-2-infected rhesus macaques suggests that age may delay or impair the induction of anti-viral cellular immune responses and delay efficient return to immune homeostasis following acute infection.

IGF-1 stimulates de novo fatty acid biosynthesis by Schwann cells during myelination

Glia ◽  
2007 ◽  
Vol 55 (6) ◽  
pp. 632-641 ◽  
Author(s):  
Guoying Liang ◽  
Gary W. Cline ◽  
Carolyn M. Macica
Keyword(s):  
Fatty Acid ◽  
Schwann Cells ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Acid Biosynthesis

scholarly journals Temperate Bacteriophages—The Powerful Indirect Modulators of Eukaryotic Cells and Immune Functions

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1013
Author(s):  
Martyna Cieślik ◽  
Natalia Bagińska ◽  
Ewa Jończyk-Matysiak ◽  
Alicja Węgrzyn ◽  
Grzegorz Węgrzyn ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Immune Modulation ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Mammalian Host ◽  
Immune Functions ◽  
Human Immune Response ◽  
Human Immune ◽  
Biological Entities

Bacteriophages are natural biological entities that limit the growth and amplification of bacteria. They are important stimulators of evolutionary variability in bacteria, and currently are considered a weapon against antibiotic resistance of bacteria. Nevertheless, apart from their antibacterial activity, phages may act as modulators of mammalian immune responses. In this paper, we focus on temperate phages able to execute the lysogenic development, which may shape animal or human immune response by influencing various processes, including phagocytosis of bacterial invaders and immune modulation of mammalian host cells.

scholarly journals The Role of Type II Fatty Acid Synthesis Enzymes FabZ, ODSCI, and ODSCII in the Pathogenesis of Toxoplasma gondii Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Pei Xu ◽  
Hany M. Elsheikha ◽  
Wen-Ge Liu ◽  
Zhi-Wei Zhang ◽  
Li-Xiu Sun ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Toxoplasma Gondii ◽  
Fatty Acid Biosynthesis ◽  
Acyl Carrier Protein ◽  
Plaque Assay ◽  
Acid Synthesis ◽  
Host Cells ◽  
Type Ii

Toxoplasma gondii is an obligate intracellular protozoan parasite, which has a worldwide distribution and can infect a large number of warm-blooded animals and humans. T. gondii must colonize and proliferate inside the host cells in order to maintain its own survival by securing essential nutrients for the development of the newly generated tachyzoites. The type II fatty acid biosynthesis pathway (FASII) in the apicoplast is essential for the growth and survival of T. gondii. We investigated whether deletion of genes in the FASII pathway influences the in vitro growth and in vivo virulence of T. gondii. We focused on beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) and oxidoreductase, short chain dehydrogenase/reductase family proteins ODSCI and ODSCII. We constructed T. gondii strains deficient in FabZ, ODSCI, and ODSCII using CRISPR-Cas9 gene editing technology. The results of immunofluorescence assay, plaque assay, proliferation assay and egress assay showed that in RHΔFabZ strain the apicoplast was partly lost and the growth ability of the parasite in vitro was significantly inhibited, while for RHΔODSCI and RHΔODSCII mutant strains no similar changes were detected. RHΔFabZ exhibited reduced virulence for mice compared with RHΔODSCI and RHΔODSCII, as shown by the improved survival rate. Deletion of FabZ in the PRU strain significantly decreased the brain cyst burden in mice compared with PRUΔODSCI and PRUΔODSCII. Collectively, these findings suggest that FabZ contributes to the growth and virulence of T. gondii, while ODSCI and ODSCII do not contribute to these traits.

scholarly journals Metabolic Adaptations During Staphylococcus aureus and Candida albicans Co-Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Kara R. Eichelberger ◽  
James E. Cassat
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Bacterial Infections ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Secondary Infection ◽  
Microbial Metabolism ◽  
Toxin Production ◽  
Metabolic Changes ◽  
Host Cells

Successful pathogens require metabolic flexibility to adapt to diverse host niches. The presence of co-infecting or commensal microorganisms at a given infection site can further influence the metabolic processes required for a pathogen to cause disease. The Gram-positive bacterium Staphylococcus aureus and the polymorphic fungus Candida albicans are microorganisms that asymptomatically colonize healthy individuals but can also cause superficial infections or severe invasive disease. Due to many shared host niches, S. aureus and C. albicans are frequently co-isolated from mixed fungal-bacterial infections. S. aureus and C. albicans co-infection alters microbial metabolism relative to infection with either organism alone. Metabolic changes during co-infection regulate virulence, such as enhancing toxin production in S. aureus or contributing to morphogenesis and cell wall remodeling in C. albicans. C. albicans and S. aureus also form polymicrobial biofilms, which have greater biomass and reduced susceptibility to antimicrobials relative to mono-microbial biofilms. The S. aureus and C. albicans metabolic programs induced during co-infection impact interactions with host immune cells, resulting in greater microbial survival and immune evasion. Conversely, innate immune cell sensing of S. aureus and C. albicans triggers metabolic changes in the host cells that result in an altered immune response to secondary infections. In this review article, we discuss the metabolic programs that govern host-pathogen interactions during S. aureus and C. albicans co-infection. Understanding C. albicans-S. aureus interactions may highlight more general principles of how polymicrobial interactions, particularly fungal-bacterial interactions, shape the outcome of infectious disease. We focus on how co-infection alters microbial metabolism to enhance virulence and how infection-induced changes to host cell metabolism can impact a secondary infection.

Inhibition of early steps of de novo fatty-acid biosynthesis by different xenobiotica

1991 ◽  
Vol 81 (2) ◽  
pp. 251-255
Author(s):  
Manfred Focke ◽  
Andrea Feld ◽  
Hartmut K. Lichtenthaler
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Acid Biosynthesis

Development of 'S', 'N’ Heterocycles as Antimycobacterials Targeting Fatty Acid Biosynthesis

2019 ◽  
Vol 15 ◽  
Author(s):  
L. K. Dahiwade ◽  
S. R. Rochlani ◽  
P. B. Choudhari ◽  
R. P. Dhavale ◽  
H. N. Moreira
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
Antimycobacterial Activity ◽  
Drug Candidate ◽  
Causative Organism ◽  
Present Communication ◽  
Acid Biosynthesis ◽  
Rational Development ◽  
After Cancer ◽  
Drug Resistant Strains

Background: Mycobacterium tuberculosis is a causative organism of tuberculosis, which is most deadly disease after cancer in a current decade. The development of multidrug and broadly drug- resistant strains making the tuberculosis problem more and more critical. In last 40 years, only one molecule is added to the treatment regimen. Generally, drug design and development programs are targeted proteins whose function is known to be essential to the bacterial cell. Objectives: Reported here are the development of 'S', 'N’ heterocycles as antimycobacterials targeting fatty acid biosynthesis. Material and Methods: In the present communication, rational development of anti-mycobacterial agent's targeting fatty acid biosynthesis has been done by integrating the pocket modelling and virtual analysis. Results: The identified potential 33 lead compounds were synthesized, characterized by physicochemical and spectroscopic methods like IR, NMR spectroscopy and further screened for antimycobacterial activity using isoniazid as standard. All the designed compounds have shown profound antimycobacterial activity. Conclusion: In this present communication, we found that 3c, 3f, 3l and 4k molecules had expressive desirable biological activity and specific interactions with fatty acids. Further optimization of these leads is necessary for the development of potential antimycobacterial drug candidate having less side effects.

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