A palaeomagnetic study of some East African rocks

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Life Cycle-Dependent Cytoskeletal Modifications in Plasmodium falciparum Infected Erythrocytes

10.1371/journal.pone.0061170PLoS ONE84

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

textabstractThe classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established. These two host responses have been studied in more detail in autoimmune diseases (AID) and show functional interactions that are of potential interest in TB immunity. In this review, we first identify the role of type 1 interferons and Th17 immunity in TB, followed by an overview of interactions between these responses observed in systemic AID. We discuss (i) the effects of GM-CSF-secreting Th17.1 cells and type 1 interferons on CCR2+ monocytes; (ii) convergence of IL-17 and type 1 interferon signaling on stimulating B-cell activating factor production and the central role of neutrophils in this process; and (iii) synergy between IL-17 and type 1 interferons in the generation and function of tertiary lymphoid structures and the associated follicular helper T-cell responses. Evaluation of these autoimmune-related pathways in TB pathogenesis provides a new perspective on recent developments in TB research

Real-time evaluation of antibacterial efficacy using bioluminescent assays for Pseudomonas aeruginosa and Staphylococcus aureus

The emergence of antibiotic resistance necessitates effective strategies for evaluating antimicrobial agents. Bioluminescent bacteria, either naturally occurring or engineered with modified reporter genes like bacterial luciferase, provide real-time assessment of bacterial viability through light emission. We investigated the antibacterial effects of cefotaxime and doxycycline using bioluminescent strains of S. aureus and P. aeruginosa, combining optical density measurements with bioluminescence monitoring. Treatment with cefotaxime resulted in a significant reduction of the bioluminescent signal in P. aeruginosa compared to untreated controls, while doxycycline induced a delayed growth curve. Both antimicrobials demonstrated strong efficacy against S. aureus, as evidenced by decreased bioluminescence signals. Results from bioluminescence assays and classical minimum inhibitory concentration and minimum bactericidal concentration methods showed consistent alignment, validating the bioluminescence approach. This study demonstrates that bioluminescence-based methods offer a reliable, real-time alternative to traditional bacterial viability assays for evaluating antimicrobial efficacy

A murine pressure ulcer model for evaluating persistence and treatment of Staphylococcus aureus infection

Chronic wounds, particularly pressure ulcers, pose significant healthcare challenges, especially in the elderly population. This study presents an experimental murine model of chronically infected pressure ulcers using a single cycle of magnet-induced ischemic injury combined with infection by bioluminescent Staphylococcus aureus. The model addresses previous limitations in studying pressure ulcer infection pathogenesis and evaluating treatment efficacy. By combining this model with in vivo imaging system (IVIS) technology, we achieved real-time, non-invasive monitoring of infection dynamics. This approach demonstrated persistent pressure ulcer wound infection and provided temporal and spatial data on infection status. To validate the model’s utility, we evaluated the antimicrobial efficacy of TCP-25, a synthetic host defense peptide, delivered in a topical gel formulation. Our findings highlight the potential of this model for investigating wound infection mechanisms, bacterial persistence, and therapeutic interventions. This innovative approach represents a significant advancement in pressure ulcer research, offering new opportunities for developing effective treatment strategies and improving patient outcomes

Bacterial control of host gene expression through RNA polymerase II

The normal flora furnishes the host with ecological barriers that prevent pathogen attack while maintaining tissue homeostasis. Urinary tract infections (UTIs) constitute a highly relevant model of microbial adaptation in which some patients infected with Escherichia coil develop acute pyelonephritis, while other patients with bacteriuria exhibit an asymptomatic carrier state similar to bacterial commensalism. It remains unclear if the lack of destructive inflammation merely reflects low virulence or if carrier strains actively inhibit disease-associated responses in the host. Here, we identify a new mechanism of bacterial adaptation through broad suppression of RNA polymerase II-dependent (Pol II-dependent) host gene expression. Over 60% of all genes were suppressed 24 hours after human inoculation with the prototype asymptomatic bacteriuria (ABU) strain E. coil 83972, and inhibition was verified by infection of human cells. Specific repressors and activators of Pol II-dependent transcription were modified, Pol II phosphorylation was inhibited, and pathogen-specific signaling was suppressed in cell lines and inoculated patients. An increased frequency of strains inhibiting Pol II was epidemiologically verified in ABU and fecal strains compared with acute pyelonephritis, and a Pol II antagonist suppressed the disease-associated host response. These results suggest that by manipulating host gene expression, ABU strains promote tissue integrity while inhibiting pathology. Such bacterial modulation of host gene expression may be essential to sustain asymptomatic bacterial carriage by ensuring that potentially destructive immune activation will not occur

New Insights into Blastocystis spp.: A Potential Link with Irritable Bowel Syndrome

International audienceBlastocystis spp. belong to the phylum Stramenopila, a complex and heterogeneous evolutionary assemblage of heterotrophic and photosynthetic protozoa [1]. Interestingly, this is the only stramenopile living in the lower digestive tract of humans, and it also lives in other mammals, birds, reptiles, amphibians, and insects [1]. Even though isolates were reported to be morphologically indistinguishable, an extensive genetic variation among isolates from both humans and animals has been observed. Thirteen subtypes (ST1-ST13), with the first nine being found in humans, have been identified based on genes coding for the small-subunit ribosomal RNA [2]. Preferential repartition of STs exists among animals that appear to constitute the main reservoir for environmental dissemination and human contamination

A broad spectrum anti-bacterial peptide with an adjunct potential for tuberculosis chemotherapy

Alternative ways to prevent and treat infectious diseases are needed. Previously, we identified a fungal peptide, NZX, that was comparable to rifampicin in lowering M. tuberculosis load in a murine tuberculosis (TB) infection model. Here we assessed the potential synergy between this cationic host defence peptide (CHDP) and the current TB drugs and analysed its pharmacokinetics. We found additive effect of this peptide with isoniazid and ethambutol and confirmed these results with ethambutol in a murine TB-model. In vivo, the peptide remained stable in circulation and preserved lung structure better than ethambutol alone. Antibiotic resistance studies did not induce mutants with reduced susceptibility to the peptide. We further observed that this peptide was effective against nontuberculous mycobacteria (NTM), such as M. avium and M. abscessus, and several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In conclusion, the presented data supports a role for this CHDP in the treatment of drug resistant organisms