European journal of microbiology & immunology最新文献

mRNA vaccines have shown high efficacy against SARS-CoV-2, yet orchestration of innate and adaptive responses in infection-naïve individuals remains incompletely characterized. Understanding these dynamics in people without prior infection is essential for defining baseline immune trajectories and providing a reference for future studies. We conducted a longitudinal study in SARS-CoV-2-naïve adults who received two doses of the BNT162b2 vaccine. Peripheral blood was analyzed by flow cytometry to quantify monocyte, NK, T, and B cell subpopulations, and serum cytokines were measured by multiplex assays. Data were evaluated with Z-score normalization and paired comparisons. Monocyte subsets segregated into two groups: one with progressive decline and another with transient activation. NK cells displayed multiphasic activation, particularly after booster. CD4+ and CD8+ T cells differentiated toward central and effector memory phenotypes, while B cells showed evidence of germinal center engagement followed by memory refinement. Cytokine fluctuations, including interferon-related signals, paralleled cellular dynamics. The booster was associated with re-engagement of innate components and amplification of adaptive responses. BNT162b2 vaccination in naïve individuals induces a coordinated sequence in innate and adaptive compartments, culminating in memory T and B cells. These findings align with current literature and provide trajectories to inform immune monitoring and optimization strategies.

Antimicrobial resistance (AMR), particularly in methicillin-resistant Staphylococcus aureus (MRSA), continues to threaten global health due to its multidrug resistance and strong biofilm-forming ability. Antimicrobial peptides (AMPs) have emerged as promising agents against MRSA biofilms because of their diverse origins, structural versatility, and unique modes of action. Natural AMPs derived from animals, plants, fungi, protists, archaea, and bacteria primarily act by disrupting bacterial membranes, interfering with quorum sensing, and downregulating biofilm-related genes such as sarA, icaA, and icaD. Synthetic AMPs, designed through computational modeling and machine learning, demonstrate enhanced stability, reduced toxicity, and improved target specificity. Synergistic AMP-antibiotic combinations, including nisin, indolicidin, and α-MSH analogs with β-lactams, significantly improve antibiofilm efficacy and bacterial clearance. Despite these advances, challenges persist due to peptide instability, enzymatic degradation, cytotoxicity, and limited in vivo validation. Recent developments in nanoparticle, hydrogel, coatings, and nanofiber delivery systems have improved AMP bioavailability and controlled release within biofilms. Continued integration of peptide engineering, nanotechnology, and bioinformatics-driven design offers promising solutions for clinical translation. Overall, AMPs represent a frontier in combating MRSA biofilms and antibiotic resistance, with future research focusing on stability enhancement, resistance prevention, and optimized therapeutic delivery.

Jorge Lobo disease (JLD) is a neglected cutaneous mycosis prevalent in the Brazilian Amazon, where limited access to histopathology delays diagnosis and care. We assessed minimally invasive punch cytology with maceration (MIPC-M), a simple procedure that uses a 1-mm punch followed by potassium hydroxide maceration and light microscopy, as a field-ready alternative. In a prospective, cross-sectional study (2014-2019) across 11 municipalities in the Brazilian Amazon, individuals ≥12 years with clinically suggestive lesions underwent three cytological approaches in parallel-adhesive tape cytology, exfoliative cytology, and MIPC-M-while histopathology served as the reference. Among 27 participants, MIPC-M identified yeast-like structures compatible with the JLD agent in 27/27 cases, yielding 100% sensitivity (95% CI, 87.2-100) versus histopathology. Adhesive tape and exfoliative cytology detected 3/27 (11.1%; 95% CI, 3.9-28.1) and 1/27 (3.7%; 95% CI, 0.7-18.3) cases, respectively. No adverse events occurred. These data support MIPC-M as a sensitive, rapid, and low-resource diagnostic option for JLD screening in remote settings. Larger studies should estimate specificity, evaluate inter-operator performance, and determine impacts on time-to-diagnosis and surgical management in Amazonian communities.

Mouse Integrin Associated Protein (MIAP) monoclonal antibodies are widely used for immunotherapeutic blockade of CD47. The anti-CD47 clones MIAP301 and MIAP410 have been studied as an immunotherapeutic treatment in the context of cancer and infectious diseases. To investigate the degree of induction of immune response afforded by these anti-CD47 clones, we treated C57BL/6 mice with MIAP301 or MIAP410, or isotype for two days and infected them with lymphocytic choriomeningitis virus (LCMV). We found that the treatment of MIAP301 led to a significant increase in mRNA expression of IFNα4 and IFNβ1 compared to MIAP410 or isotype. Our study further revealed that MIAP301 treatment enhanced the numbers of CD11b+ macrophages and CD11c+ dendritic cells, as well as improved phagocytic capacity. Analysis of NK and T cells showed a subtle difference, and a significantly increased IFN-γ+ NK cell in the mice treated with MIAP301. Both anti-CD47 antibodies significantly increased NK cells, CD8+, and CD4+ T cells quantity and quality when compared to isotype. Overall, our findings indicate that MIAP301 treatment significantly increases myeloid innate immune signaling compared to MIAP410 treatment. Considering the evolving preclinical studies using anti-CD47 for therapy, our study findings may be important when deciding which clone to use.

Antibiotics have revolutionized medicine and drastically reduced mortality from bacterial infections. However, the widespread misuse of antibiotics in human and veterinary medicine, but also farming has greatly accelerated the emergence of multidrug-resistant (MDR) pathogens hampering treatment of infectious diseases. Therefore, novel anti-infectious treatment concepts applying antibiotic-independent natural compounds are highly appreciated. Ginger (Zingiber officinale Roscoe) has been proposed as such promising candidate given its health-beneficial including anti-microbial effects. Therefore, our systematic literature review summarizes current evidence for anti-bacterial effects of ginger and derived molecules to elaborate perspectives for treatment options of infectious diseases caused by bacterial pathogens. The included 22 articles revealed that defined ginger extracts, essential oils, and distinct molecules including gingerol and shogaol i) inhibited growth of Gram-positive and Gram-negative bacteria including MDR isolates and ii) reduced distinct bacterial virulence factors including biofilm formation. Furthermore, iii) application of ginger together added to other plant-derived compounds or synthetic antibiotics markedly enhanced anti-bacterial effects of the latter, whereas iv) ginger could also exert immune-modulatory including anti-inflammatory and anti-oxidant activities in vitro and in vivo. In conclusion, ginger-derived molecules constitute promising alternative or adjunct antibiotics-independent options in the combat of infectious diseases caused by bacterial pathogens including MDR strains.

Background: The pharmacotherapy of cutaneous leishmaniasis is invasive and presents several adverse reactions, which reinforces the need for topical and less toxic alternatives.

Methods: Topical microemulsions containing phenolic compounds from Libidibia ferrea (Fabaceae) were developed, physicochemically characterized, and tested in hamsters (Mesocricetus auratus) experimentally infected with Leishmania amazonensis. After treatment, clinical progression of lesions, histopathological alterations, and parasite load were evaluated. The dichloromethane (DCM) fraction of the extract was analyzed by mass spectrometry, and the main compounds were isolated.

Results: The optimized microemulsion effectively controlled lesion progression, showing only a 25% increase in lesion volume, compared to a 383% increase for the group without treatment, and presented a moderate inflammatory response. A new phenolic compound, named libidine (phenylpropanoic acid derivative), along with methyl gallate, was isolated from the DCM fraction.

Conclusions: The topical formulation was as effective as Glucantime® (antimonial standard treatment) and produced a significant reduction in parasite load, consistent with the antileishmanial activity previously reported for phenolic acids and their derivatives.

Background: The potential aetiological relevance of Blastocystis spp. and Dientamoeba fragilis in the human intestine, and their possible associations with Campylobacter spp. and Giardia duodenalis, remain unclear. By incorporating Bayesian priors to account for diagnostic test accuracy, we statistically analysed the interactions among these microorganisms.

Methods: Diagnostic test accuracy data were derived from multiple PCR assays and incorporated as priors to adjust for non-differential misclassification. Bayesian odds ratios and relationships based on DNA quantity were assessed for a dataset of 1,065 stool samples containing at least one of the four target microorganisms.

Results: Accounting for diagnostic test accuracy resulted in wide credibility intervals. Blastocystis spp. were negatively associated with G. duodenalis. G. duodenalis was most often detected in the absence of Blastocystis spp. and D. fragilis, whereas detection of Blastocystis spp. was associated with lower Campylobacter spp. DNA abundance. A negative association between Blastocystis spp. and Campylobacter spp. was observed only in the absence of D. fragilis.

Conclusion: The assumed variation in detection rates of Campylobacter spp. and G. duodenalis based on the presence of Blastocystis spp. and/or D. fragilis was confirmed. Future epidemiological studies should explore interactions among multiple microorganisms using robust statistical approaches.

Staphylococcus aureus is a clinically important bacterial pathogen causing infections from superficial skin lesions to life-threatening systemic diseases. The emergence of methicillin-resistant S. aureus (MRSA) has compounded the global health burden, particularly in low- and middle-income countries, as its quorum-sensing (QS) mediated mechanisms contribute to its persistence, resistance, and evasion from host immune responses and antimicrobial treatments. Thus, these features compromise the effectiveness of conventional antibiotics, urging the need for alternative therapeutic approaches. To resolve these issues, several non-antibiotic antibiofilm approaches have been developed. Bacteriophages and phage-derived enzymes show promising specificity in lysing bacterial cells and disrupting biofilms. Antimicrobial peptides (AMPs), with their broad-spectrum activity, destabilize bacterial membranes and modulate immune responses. Monoclonal antibodies can neutralize toxins or inhibit adhesion molecules within biofilms. Phytochemicals have demonstrated activity against QS pathways and efflux pumps. Metal ion chelators like deferiprone interfere with iron acquisition, which is essential for biofilm stability. Nanoparticles (NPs), ranging from metallic and polymeric to lipid-based and cyclodextrin-based systems, enhance drug delivery and biofilm penetration. CRISPR-Cas systems provide precise genome editing to target resistance genes and virulence factors. Rhamnolipids disrupt biofilm matrix integrity, while enzymes such as dispersin B degrade extracellular polymeric substances. Photodynamic and laser therapies offer localized disruption of biofilm structures through oxidative stress. Collectively, this review offers a transformative complementary approach to traditional antibiotics, enhancing treatment efficacy while potentially reducing the emergence of resistance. Continued research on delivery systems, safety profiles, and synergistic combinations will be pivotal for their clinical translation against S. aureus infections.

Background: A cross-sectional study was performed to investigate associations of enteric colonization with resistant bacteria in Ghanaian individuals who were tested positive and negative for the human immunodeficiency virus (HIV).

Methods: Abundance of the ESBL-(extended spectrum beta-lactamase-)type resistance-mediating gene blaCTX-M and the vancomycin resistant enterococci-(VRE-)associated genes vanA and vanB genes was associated with available clinical and epidemiological data on the study participants.

Results: In terms of enteric carriage of ESBL-positive bacteria with CTX-M-type beta-lactam resistance genes, being HIV-positive (93.3% vs. 83.3%, P = 0.003) and having low CD4+ T-lymphocyte counts <200 cells/µL (microliter) (96.8% vs. 91.2%, P = 0.009) were identified as risk factors. Enteric carriage of ESBL-positive bacteria with CTX-M-type resistance genes was associated with poor immunological status in terms of lower CD4+ T-leukocyte counts, lower CD4+/CD8+ ratios, higher viral replication, as well as with immune activation. For VRE, a non-significant trend for more VRE in control individuals without known HIV infection (6% vs. 2.5%, P = 0.089) was observed.

Conclusions: An association of ESBL colonization and immunological status was recorded. No such association was detected for VRE, suggesting different determinants of local VRE epidemiology.

Chronic degenerative diseases including osteoarthritis are on the rise leading to a growing demand for joint replacement surgery in elderly and often multimorbid patients. Periprosthetic joint infections (PJIs) constitute serious complications following endoprosthetic surgery. Increasing prevalences of PJIs by multi-drug resistant and/or biofilm-producing bacteria hinder sufficient anti-infectious treatment especially in vulnerable patients. Hence, alternative and/or adjunct therapeutic approaches appear crucial in the combat of difficult-to-treat PJIs. In our review we summarize recent evidence for changes in the spectrum of PJI-associated pathogens over time and elucidate treatment concepts beyond established standard therapies. Our literature search revealed that the spectrum of bacterial pathogens can vary considerably depending on the time course post-surgery, the geographical region, and the patient population. While standard antibiotic therapy besides surgical revision remains the corner stone of treatment, alternative/adjunct antibiotics-independent methods are increasingly coming to the fore. These include the targeted dissolution of bacterial biofilms, enzyme-based approaches, and enhanced infection prevention measures upon risk assessment of the patient. Despite promising methodological approaches clinical evidence of their therapeutic value in everyday care is scarce. Hence, optimized early pathogen detection measures, individually tailored treatment concepts and their application in interdisciplinary settings will be important in the combat of difficult-to-treat PJIs.