bims-bac4me 2025-08-24 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2025–08–24
thirteen papers selected by
Chun-Chi Chang, Lunds universitet

Gut commensal microbiota drive tailored macrophage responses.
A systems approach for elucidating the role of the microbiome in epigenetic cellular memory.
Long-term hyperglycaemia exerts contrasting effects on M1- and M2-like macrophages.
The intracellular agent of Q fever, Coxiella burnetii, alters human alveolar macrophage metabolism and mitochondrial physiology.
TLR9-Driven S-Palmitoylation in Dendritic Cells Reveals Immune and Metabolic Protein Targets.
Identification of novel protein biomarkers of macrophage polarization using comparative proteomic analyses of murine primary macrophages.
Prior appendectomy attenuates the immune protective efficacy of BCG vaccination against Mycobacterium tuberculosis infection.
FGF15/FGFR4 signaling suppresses M1 macrophage polarization and multi-organ inflammation in septic mice by inhibiting H3K18 lactylation-driven Irf7 expression through NF2-Hippo activation.
Tissue-Resident Macrophage and Dendritic Cell Cooperation Drives Type I IFN Immunity to Enteroviruses in the Liver.
The Synergistic Role of P2rx7 and Panx1 in Regulating Alveolar Macrophage Pyroptosis and Exosome-Mediated Ferroptosis of Alveolar Epithelial Cells in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome.
Extracellular Vesicles Containing MDP Derived from Lactobacillus rhamnosus GG Inhibit HSV-2 Infection by Activating the NOD2-IFN-I Signalling Pathway.
Role of methicillin-resistant Staphylococcus aureus in cutaneous infections: Current treatments and therapeutic approaches for future advancement.
Differential nasopharyngeal microbiota patterns: A Comparative Study of Pneumococcal Pneumonia, COVID-19, and Healthy Adults.

Cell Rep. 2025 Aug 18. pii: S2211-1247(25)00928-3. [Epub ahead of print]44(8): 116157

Gut commensal microbiota drive tailored macrophage responses.

Josh Jones, Karla Y García-Martínez, Yi-Yuan Lee, Matt Rhee, Rahul R Nath, Sola Takahashi, Benjamin Grodner, Iwijn De Vlaminck, Cynthia A Leifer, Ilana L Brito.

  Macrophages serve as sentinels at the intestinal surface, responding to organismal cues to drive proinflammatory or tolerogenic responses. To date, studies of combinations of these cues do not fully capture the heterogeneity of macrophage responses. To address this gap, we performed multiplexed single-cell RNA sequencing on 74,476 human monocyte-derived macrophages following exposure to 15 bacteria, mostly commensals. We observe clusters that appeared only after macrophage exposure to bacteria, and transcriptional responses within each cluster varied by species and Gram status. The proportion of each cluster also varied among exposure conditions. Macrophages exposed to defined combinations of organisms revealed that Fusobacterium nucleatum drives inflammatory responses, whereas Mediterraneibacter gnavus tempers them. Overall, our results show that macrophages distinguish between commensal organisms, relevant to intestinal diseases characterized by altered microbiome compositions. This sequencing dataset will be a useful resource to probe human macrophage response to a broad range of bacteria.

Keywords:  CP: Immunology; CP: Microbiology; TLR; bacteria; commensals; cytokine; inflammation; macrophages; microbiome; mucosal; scRNA-seq; transcriptomes

DOI:  https://doi.org/10.1016/j.celrep.2025.116157
mSystems. 2025 Aug 18. e0018525

A systems approach for elucidating the role of the microbiome in epigenetic cellular memory.

Jacob W Pederson, Aleksandra Nita-Lazar.

  The microbiome plays an essential role in the development of the immune system. Both the immune system and microbiome dynamically respond to internal and external cues, and dysregulation of either of these systems can lead to disease pathology. Separate from the adaptive immune system, the innate immune system retains a memory of inflammatory events that determine the quality of future immune responses. The phenomenon is characterized by epigenetic modifications that lead to immunosuppressive or hyperinflammatory cell phenotypes, collectively designated as epigenetic cellular memory. It remains unclear whether and how the microbiome influences epigenetic cellular memory phenotypes to promote immunopathology and chronic disease. Inflammatory signals from the microbiota regulate hematopoiesis and systemic immunity through the production of immunomodulatory ligands and activation of circulating immune cells; however, few studies have directly implicated these mechanisms in the development of epigenetic cellular memory. We posit that a multi-omic systems approach is well-suited to elucidating the complex factors mediating the microbiome's contribution to this phenomenon. By measuring responses to exogenous influences through multi-omic technologies, it will be possible to identify the regulatory axis that next-generation therapies should target to reverse immunopathology. As chronic inflammatory disorders are on the rise, it is imperative that future therapies leverage both dietary and pharmacological interventions to promote self-reinforcing homeostatic immunity by targeting the mechanisms of epigenetic cellular memory.

Keywords:  immune memory; innate immunity; microbiome; systems biology

DOI:  https://doi.org/10.1128/msystems.00185-25
Front Immunol. 2025 ;16 1639650

Long-term hyperglycaemia exerts contrasting effects on M1- and M2-like macrophages.

Sona Margaryan, David Poghosyan, Susanna Ghonyan, Lina Hakobyan, Anush Martirosyan, Gayane Manukyan.

   Introduction: Chronic hyperglycemia can contribute to metabolic disorders, disrupting cellular homeostasis and potentially leading to immunological disturbances. As highly adaptable innate immune cells, macrophages can effectively utilize glucose for energy and adjust their activities in response to environmental changes. We hypothesized that hyperglycemia induces distinct effects on M1 and M2 macrophages, thereby promoting their divergent roles in the inflammatory response.
Methods: For this, we applied an in vitro hyperglycemia model to investigate its impact on M1- and M2-like macrophages differentiated from primary monocytes.
Results: M1-like macrophages exhibited diminished capacity to produce reactive oxygen species (ROS), IL-6, TNF-α, as well as reduced antigen presentation and co-stimulatory abilities under long exposure to high glucose. In contrast, M2-like macrophages showed a shift toward M1 polarization, characterized by increased production of ROS and IL-6, upregulation of CD86 and HLA-DR expression, and reduced reparative abilities. We also observed disturbance of endotoxin tolerance evidenced by increased production of TNF-α and diminished phagocytic ability.
Discussion: The results suggest that hyperglycemia disrupts the typical functional dichotomy of M1 and M2 macrophages, which may explain mixed polarization of tissue macrophages in individuals with metabolic syndromes associated with chronic hyperglycemia.

Keywords:  GM-CSF and M-CSF-derived cells; LPS; M1 and M2 macrophages; endotoxin tolerance; hyperglycemia; phagocytosis

DOI:  https://doi.org/10.3389/fimmu.2025.1639650
mBio. 2025 Aug 18. e0143625

The intracellular agent of Q fever, Coxiella burnetii, alters human alveolar macrophage metabolism and mitochondrial physiology.

Het Adhvaryu, Lu Huang, Carrie M Long, Daniel E Voth.

  Coxiella burnetii, the etiologic agent of Q fever, is a gram-negative intracellular bacterium that infects humans via contaminated aerosols typically while working with livestock. C. burnetii initially targets alveolar macrophages (AMs) to establish a growth niche within a phagolysosome-like compartment termed the Coxiella-containing vacuole (CCV). C. burnetii deploys a type IV secretion system (T4SS) to secrete effector proteins that control host cell functions to benefit the bacterium, orchestrating an immunosuppressive, pro-bacterial environment for replication to high numbers. Although multiple signaling pathways have been characterized in the context of C. burnetii infection, the role of host cell metabolic function in establishing favorable intracellular conditions is undefined. Using a primary human AM model, we show that C. burnetii maintains host oxidative phosphorylation (OXPHOS) at homeostasis in a T4SS-dependent manner. Inhibiting OXPHOS impairs CCV expansion, while preventing glycolysis and fatty acid oxidation does not alter vacuole development. Interestingly, mitochondria are shorter in infected cells, suggesting C. burnetii manipulates mitochondrial function to regulate host metabolism. Finally, endoplasmic reticulum (ER) stress regulates immunosuppressive macrophage activities, and C. burnetii regulates ER stress in a T4SS-dependent manner. Here, we show the involvement of protein kinase R-like endoplasmic reticulum kinase in regulating OXPHOS during infection. Collectively, our results demonstrate that C. burnetii engages human macrophage metabolic processes to establish a replication niche.IMPORTANCECoxiella burnetii causes human Q fever and is a potential bioterrorism threat. In humans, C. burnetii evades host cell killing and establishes a prolonged replication cycle within AMs, which is a critical step toward presentation of acute or chronic disease symptoms. While macrophage metabolism fuels antibacterial activity, we identified key metabolic processes that C. burnetii manipulates to sustain a pro-bacterial growth niche. Currently, few infection models capture C. burnetii interaction with disease-relevant human cells. Here, we used the established primary human AM infection system to characterize bacterial modulation of macrophage metabolism. Our findings advance understanding of C. burnetii-AM interactions and lay the foundation for future therapeutic exploration.

Keywords:  Coxiella burnetii; PERK; macrophage; metabolism; mitochondria

DOI:  https://doi.org/10.1128/mbio.01436-25
Eur J Immunol. 2025 Aug;55(8): e70039

TLR9-Driven S-Palmitoylation in Dendritic Cells Reveals Immune and Metabolic Protein Targets.

Juan N Quiroz, Malte Sielaff, Daria Kondrateva, Fatima Boukhallouk, Gloria J Godoy, Cecilia R Molina, Brecht Moonen, Claudia C Motran, Jeroen Bogie, Hugo D Luján, Stefan Tenzer, Tim Sparwasser, Luciana Berod.

  Dendritic cells (DCs) rely on Toll-like receptor 9 (TLR9) to detect unmethylated CpG motifs in microbial DNA, triggering essential immune responses. While the downstream signaling pathways of TLR9 activation are well characterized, their impact on S-palmitoylation is unknown. S-palmitoylation, involving the reversible attachment of palmitic acid to cysteine residues, plays a crucial role in regulating protein function and is catalyzed by the ZDHHC family of palmitoyl-acyltransferases (PATs). In this study, we investigated the S-palmitoylated proteome of bone marrow-derived GM-CSF DCs (GM-DCs) at resting and following TLR9 activation with CpGB. Using the click-chemistry-compatible analog 17-octadecynoic acid (17-ODYA) and mass spectrometry (MS)-based proteomics, we characterized dynamic remodeling of S-palmitoylation in response to TLR9 activation. This included enrichment of targets involved in immune and metabolic pathways. Transcriptomic analysis of mice and human DCs revealed TLR9-driven modulation of PAT-encoding genes. Subsequently, we explored the contribution of Zdhhc9 expression to the regulation of S-palmitoylation in DCs. Using gene knockout approaches, we identified candidate protein targets potentially linked to ZDHHC9 activity. Interestingly, modulation of Zdhhc9 expression alone did not influence DC maturation, suggesting that other PATs might compensate for its activity. Together, our findings reveal a novel layer of regulation in TLR9 signaling mediated by S-palmitoylation.

Keywords:  S‐palmitoylation; TLR9 signaling; dendritic cells; innate immunity

DOI:  https://doi.org/10.1002/eji.70039
J Immunol. 2025 Aug 18. pii: vkaf202. [Epub ahead of print]

Identification of novel protein biomarkers of macrophage polarization using comparative proteomic analyses of murine primary macrophages.

Baolong Liu, Phuong Linh Nguyen, Pengfei Li, Michael J Naldrett, Sophie Alvarez, Jiujiu Yu.

  Macrophages comprise the first line of host responses against injury and pathogens and therefore are critically engaged in tissue repair, host defense, and homeostasis maintenance. Depending on the surrounding microenvironment, macrophages polarize into a wide spectrum of immunophenotypes with 2 extreme opposite ends-proinflammatory M1 and anti-inflammatory M2. Elucidating the biochemical bases of distinct macrophage immunophenotypes, as well as discriminating between these phenotypes, are paramount to understanding the contributions of macrophage subpopulations to health and diseases. In this study, murine bone marrow-derived macrophages were treated with LPS or IL-4 to induce the M1/M(LPS) or M2/M(IL-4) state, respectively. Comparative proteomic analyses demonstrate that M1 and M2 macrophages have their own unique protein landscapes. The signature proteins of M1 and M2 macrophages are engaged in distinct signaling pathways, which offer the biochemical bases for their specialized functions. The plasma membrane proteins Clec4e and Cd72 are identified as new biomarkers to discriminate murine M1 and M2 macrophages, respectively. Comparison of the proteomes of murine and human macrophages leads to identification of 2 new shared M1 biomarkers, Gbp2/GBP2 and Acod1/ACOD1. In addition, CLEC4E is validated as a new M1 biomarker for human primary macrophages. This study provides an unbiased protein dataset of murine primary M1/M(LPS) and M2/M(IL-4) macrophages for future research in macrophage biology. The plasma membrane localization of the new biomarkers Clec4e and Cd72 facilitates their labeling and detection. The new M1 biomarkers shared by human and mouse primary macrophages have potential broad applications in both basic research and clinical practice.

Keywords:  biomarkers; human primary macrophages; macrophage polarization; murine primary macrophages; proteomics

DOI:  https://doi.org/10.1093/jimmun/vkaf202
Immunobiology. 2025 Aug 08. pii: S0171-2985(25)00240-2. [Epub ahead of print]230(5): 153106

Prior appendectomy attenuates the immune protective efficacy of BCG vaccination against Mycobacterium tuberculosis infection.

Huirong Huang, Wei Xu, Sidong Xiong.

  Cecal appendix is a unique niche for commensal bacteria, and has been considered the primary site for immunoglobulin A production. Yet its immune function in anti-infection immunity has not been fully understood. In order to elucidate whether cecal patch (CeP), the murine version of appendix, would influence the immune response induced by Mycobacterium tuberculosis (M. tb) and the vaccine effect of Bacillus Calmette-Guérin (BCG), BALB/c mice at 4 weeks of age received appendectomy or sham operation and recovered for 2 weeks before intranasal infection with 2 × 107 CFU Mycobacterium tuberculosis H37Ra. Appendectomy of mice led to a reduction in lung macrophage numbers 7 days post infection (p. i.), and aggravated lung immunohistopathology 4 weeks p. i.. Appendectomized mice vaccinated with 5 × 106 CFU BCG exhibited attenuated BCG-specific serum IgG, reduced lung/splenic IFN-γ+ T response, and weakened T proliferation and cytotoxicity, and eventually worsened lung pathology compared to sham operated mice. Mechanistically, we found that appendectomized mice at a young age (4 weeks) had an attenuated maturation of mesenteric lymph node (MLN) conventional dendritic cells (cDCs), which accounted for the impaired systemic IFN-γ+ T response and cytotoxicity against M. tb. Our data suggest that intact appendix maintain intestinal DC maturation and systemic Th1 induction against M. tb and has an assistant role in increasing immune efficiency of BCG vaccine.

Keywords:  Appendectomy; BCG; Cecal patch; Dendritic cells; Mycobacterium tuberculosis

DOI:  https://doi.org/10.1016/j.imbio.2025.153106
Cell Death Dis. 2025 Aug 19. 16(1): 628

FGF15/FGFR4 signaling suppresses M1 macrophage polarization and multi-organ inflammation in septic mice by inhibiting H3K18 lactylation-driven Irf7 expression through NF2-Hippo activation.

Bo Li, Jiayu Li, Zexiang Zhu, Yong Tang, Yun Zhou, Geshu Du, Xing Li.

M1 macrophage polarization plays a key role in the onset and progression of sepsis. Fibroblast growth factor 15 (FGF15) suppresses septic inflammation through its FGF receptor 4 (FGFR4); however, the underlying mechanisms are largely unclear. In this study, we evaluated the anti-inflammatory effects of recombinant FGF15 (rFGF15) in cecal ligation and puncture (CLP)-induced septic mice in vivo, as well as lipopolysaccharide (LPS)-stimulated mouse bone marrow-derived macrophages (BMDMs) and RAW264.7 macrophages in vitro. We observed that rFGF15 suppressed M1 macrophage polarization and associated inflammatory responses in both CLP-induced septic mice and LPS-stimulated BMDMs and RAW264.7 macrophages. Additionally, macrophage-depleted CLP mice transplanted with LPS-stimulated BMDMs pre-treated with rFGF15 exhibited reduced multi-organ inflammation and enhanced survival compared to those receiving LPS-stimulated BMDMs without rFGF15 treatment. Mechanistically, FGF15 activated the neurofibromin 2 (NF2)-Hippo pathway through FGFR4, leading to the inhibition of glycolysis, lactate production, and histone H3K18 lactylation. This led to reduced expression of interferon regulatory factor 7 (Irf7), a key regulator of type I interferon responses. In conclusion, FGF15 suppresses M1 macrophage polarization and associated inflammatory responses in sepsis by activating the NF2-Hippo pathway, thereby inhibiting H3K18 lactylation-driven Irf7 expression. FGF15 holds promise as a potential innovative therapy for sepsis.

DOI: https://doi.org/10.1038/s41419-025-07962-w
bioRxiv. 2025 Aug 12. pii: 2025.08.12.669977. [Epub ahead of print]

Tissue-Resident Macrophage and Dendritic Cell Cooperation Drives Type I IFN Immunity to Enteroviruses in the Liver.

Emma Heckenberg, Jacob G Davis, Caitlin Hale, Carolyn B Coyne.

Enteroviruses are major causes of neonatal morbidity and mortality, with echovirus infections commonly associated with severe disease, including acute liver failure. The human neonatal Fc receptor (hFcRn) is the primary receptor for echoviruses, and its expression is required for infection of the liver in mouse models. While type I interferons (IFNs) are known to protect against echovirus-induced disease, the specific innate immune cells responsible for initiating this antiviral signaling in the liver remain undefined. To dissect the relative contributions of type I and type III IFNs in protecting the liver during echovirus infection, we combined in vivo mouse models (expressing hFcRn and deficient in Ifnar1, Ifnlr1, or both) with single cell RNA sequencing (scRNA-seq). This approach enabled us to pinpoint the hepatic cell types targeted by echoviruses and to identify the specific cells producing IFNs in response. We found that hepatocytes and Kupffer cells were the most heavily infected cell types. In contrast, early and robust type I IFN responses were primarily driven by Kupffer cells and a subset of dendritic cells. To determine whether type I IFNs act directly on hepatocytes to mediate protection, we generated conditional knockout mice lacking Ifnar1 specifically in hepatocytes. These mice showed similar morbidity, mortality, and hepatic viral titers as whole-body Ifnar1 ⁻/⁻ animals, indicating that hepatocytes depend on protective IFN signals produced by immune cells during echovirus infection. These findings uncover cell-type-specific mechanisms by which echoviruses subvert host immunity and show how dysregulated IFN responses drive liver pathology and neonatal mortality.

DOI: https://doi.org/10.1101/2025.08.12.669977
FASEB J. 2025 Aug 31. 39(16): e70904

The Synergistic Role of P2rx7 and Panx1 in Regulating Alveolar Macrophage Pyroptosis and Exosome-Mediated Ferroptosis of Alveolar Epithelial Cells in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome.

Haiyan Rao, Qunhua Ding, Annan Liu, Huijun Qiu, Jinghua Luo.

  Acute respiratory distress syndrome (ARDS) represents a severe pulmonary condition characterized by widespread alveolar injury and inflammatory cascade activation. While alveolar macrophages and epithelial cells are recognized as critical mediators in ARDS pathogenesis, the molecular mechanisms underlying their dysfunction remain incompletely understood. This study investigated the regulatory role of the P2rx7-Panx1 signaling axis in orchestrating alveolar macrophage pyroptosis and subsequent exosome-mediated ferroptosis of alveolar epithelial cells in lipopolysaccharide (LPS)-induced ARDS. The study utilized both an in vivo ARDS mouse model and in vitro systems comprising MH-S alveolar macrophages and MLE-12 alveolar epithelial cells. P2rx7-Panx1 interaction was characterized through Western blot analysis, immunofluorescence microscopy, and co-immunoprecipitation studies. The functional consequences of P2rx7 and Panx1 depletion were assessed through comprehensive analyses of cell viability, inflammatory cytokine profiles, oxidative stress parameters, and protein expression patterns. LPS exposure induced significant upregulation and enhanced interaction of P2rx7 and Panx1 in alveolar macrophages both in vivo and in vitro. Selective knockdown of either P2rx7 or Panx1 significantly attenuated LPS-induced macrophage pyroptosis, as evidenced by reduced cell death, diminished NLRP3/ASC/caspase-1 activation, and decreased IL-1β/IL-18 secretion, with dual knockdown exhibiting synergistic protection. Furthermore, LPS-stimulated macrophages induced ferroptosis in alveolar epithelial cells through P2rx7-dependent exosome release, while P2rx7 blockade effectively prevented this exosome-mediated epithelial cell ferroptosis. This study elucidates a novel mechanism whereby the P2rx7-Panx1 axis synergistically regulates LPS-induced alveolar macrophage pyroptosis through caspase-11-dependent pathways. Moreover, P2rx7 functions as a critical modulator of exosome release from alveolar macrophages, thereby promoting ferroptotic death of alveolar epithelial cells. These findings identify the P2rx7-Panx1 signaling axis as a promising therapeutic target in ARDS treatment.

Keywords:  P2rx7; Panx1; acute respiratory distress syndrome; alveolar macrophages; exosomes; ferroptosis; pyroptosis

DOI:  https://doi.org/10.1096/fj.202403385RR
J Extracell Vesicles. 2025 Aug;14(8): e70152

Extracellular Vesicles Containing MDP Derived from Lactobacillus rhamnosus GG Inhibit HSV-2 Infection by Activating the NOD2-IFN-I Signalling Pathway.

Jingyu Wang, Haoming Chen, Mei Huang, Yuqi Du, Ruyi Zhang, Yiyi Huang, Yuling Lin, Ruoru Pan, Yubing Wang, Wanqin Cui, Qian Wang, Lei Zheng, Xiumei Hu.

  The immune evasion strategies and lifelong latency of herpes simplex virus type 2 (HSV-2) present significant challenges for effective treatment. Recent studies have demonstrated that the commensal microbiota plays an important role in regulating immunity against viral infections. We previously reported that Lactobacillus rhamnosus GG (LGG) activates the expression of type I interferons (IFN-I) to inhibit HSV-2 infection. However, the specific molecular mechanisms remain unclear. Bacterial extracellular vesicles (EVs) are small lipid bilayer-bound particles secreted by bacteria, which can serve as intercellular communication vehicles between the host and pathogens, functioning as immunomodulatory vectors defending against viral infections. In this study, we confirmed that LGG-EVs activate the nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)-IFN-I signalling pathway, inducing the expression of interferon-stimulated genes (ISGs) to combat HSV-2 infection both in vivo and in vitro. Furthermore, we explored the specific components within LGG-EVs and identified the presence of muramyl dipeptide (MDP). We demonstrated that MDP-enriched LGG-EVs effectively inhibit HSV-2 infection via activation of the NOD2-IFN-I pathway. These findings suggest that LGG-EVs could serve as a novel therapeutic strategy for HSV-2 and provide a mechanistic foundation for future antiviral research.

Keywords:  Lactobacillus rhamnosus GG; NOD2; extracellular vesicles; herpes simplex virus type 2; type I interferons

DOI:  https://doi.org/10.1002/jev2.70152
Int J Pharm. 2025 Aug 14. pii: S0378-5173(25)00867-1. [Epub ahead of print] 126030

Role of methicillin-resistant Staphylococcus aureus in cutaneous infections: Current treatments and therapeutic approaches for future advancement.

Adviti Thomas, Nour Almsallaty, Tamim Chalati, Joshua Boateng, Asma Buanz, Ana Maria Totea.

  Antibiotics are often prescribed as a first-line treatment for bacterial skin infections, particularly in severe and persistent cases. However, the ability of the pathogen to develop antibiotic resistance complicates the treatment of these diseases. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the primary microorganisms implicated in skin and soft tissue infections, such as Cellulitis, Impetigo, and infections secondary to Atopic Dermatitis (AD) and has exerted significant pressure on the healthcare industry due to its resistance to conventional antibiotics, including beta-lactams. Skin infections caused by this Gram-positive superbug can occur in individuals even without commonly known risk factors, and thus, there is an urgent necessity to develop novel therapeutic strategies that function beyond traditional antibiotics. Research on alternative treatments, including plant-derived compounds, antimicrobial peptides (AMPs), bacteriophages, and antibiotic sensitisers, is garnering attention as a promising and innovative approach. Numerous studies have demonstrated the capacity of these compounds to inhibit pathogenic bacteria like MRSA. These novel compounds target bacteria through diverse mechanisms, inhibit biofilm formation, and mitigate resistance development. Topically administered treatments are preferred for MRSA-related skin infections; however, cytotoxicity, skin penetration, and in vivo efficacy testing remain a significant challenge. This review provides an overview of the mechanisms contributing to the pathogenesis of MRSA skin infections and investigates alternative therapeutic options to the common antibiotics. An indirect antibacterial approach that uses conventional antibiotics combined with non-antibiotics aims to enhance therapeutic efficacy and overcome resistance by disrupting bacterial defences and biofilm formation, thereby reducing the required antibiotic dosage and minimising adverse effects.

Keywords:  Antibiotic resistance; Antibiotic sensitizers; Antimicrobial peptide; Bacteriophages; Essential oils; Methicillin-resistant Staphylococcus aureus; Non-steroidal anti-inflammatory drugs; Plant compounds; Soft-skin tissue infection; Synergy

DOI:  https://doi.org/10.1016/j.ijpharm.2025.126030
J Infect. 2025 Aug 14. pii: S0163-4453(25)00189-6. [Epub ahead of print] 106589

Differential nasopharyngeal microbiota patterns: A Comparative Study of Pneumococcal Pneumonia, COVID-19, and Healthy Adults.

Beatriz Dietl, Desirée Henares, Eva Cuchí, Miguel Blanco-Fuertes, Mireia Rajadell, Pedro Brotons, Aleix Lluansi, Lucía Boix-Palop, Esther Calbo, Carmen Muñoz-Almagro.

   INTRODUCTION: Lower respiratory infections (LRIs) rank among the leading causes of mortality worldwide. Many microorganisms responsible for LRIs, such as Streptococcus pneumoniae and respiratory viruses, exhibit variable behaviour: they can exist as asymptomatic colonizers, cause mild disease, or lead to severe invasive infections. Various factors influence the clinical manifestations and severity of LRIs. Emerging evidence suggests that the nasopharyngeal microbiota (NM) plays a crucial role in these processes. This study aims to identify microbiota profiles associated with respiratory health and disease.
METHODS: A prospective case-control study was conducted between February 2021 and September 2022. NM samples were collected from adults with pneumococcal pneumonia (PPn), COVID-19 pneumonia (CPn), and healthy controls (HC). Samples were analyzed using 16S rRNA gene sequencing. Participants were matched for age and gender. Random Forest modelling was applied to microbiota data to distinguish pneumococcal pneumonia from viral community-acquired pneumonia (CAP).
RESULTS: A total of 129 samples were analyzed, including 38 from PPn cases, 54 from CPn cases, and 37 from HC. While age and sex distributions were similar across groups, comorbidities, immunosuppression, and prior infections were more common among cases. Alpha-diversity analysis revealed no significant differences in species richness or evenness across groups. However, beta-diversity analysis showed distinct microbial compositions: Corynebacterium was predominant in CPn patients, whereas Streptococcus was more abundant in PPn patients compared to HC.
CONCLUSIONS: The nasopharyngeal microbiota differs significantly in adults with pneumococcal pneumonia compared to those with COVID-19 pneumonia and healthy controls. These findings suggest the importance of specific bacterial genera in the progression from asymptomatic colonization to disease. A deeper understanding of healthy nasopharyngeal microbiota profiles could have substantial implications for the prevention and treatment of respiratory infections.

Keywords:  COVID-19; Nasopharynx; Pneumonia, pneumococcal; microbiota; pneumonia

DOI:  https://doi.org/10.1016/j.jinf.2025.106589