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Results for “polymicrobial interactions”

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PubMed2026

Pseudomonas aeruginosa adaptation and persistence in the aspergilloma microbiome revealed by integrated multi-omics.

Chronic pulmonary aspergillosis involves the formation of a fungal ball (aspergilloma) in lung cavities. Pseudomonas aeruginosa commonly co-colonizes these lesions; however, the in vivo mechanisms underlying its persistence are unknown. Using a multi-omics approach on resected aspergillomas, we defined the genomic, transcriptional, and metabolic adaptations of P. aeruginosa within this polymicrobial niche. We reconstructed high-quality P. aeruginosa genomes and identified a conserved core genome, along with accessory genes for secondary metabolism, virulence, and antimicrobial resistance. Phylogenomics revealed heterogeneous evolutionary paths among co-colonizing strains. Metatranscriptomics showed stark physiological heterogeneity, from metabolically aggressive to stress-adapted states. High expression of phenazine, quorum-sensing (PQS), siderophore, and secretion-system operons was corroborated by metabolomic detection of phenazine-1-carboxylic acid and 2-heptylquinolin-4(1H)-one, confirming active bacterial antagonism in vivo. Concurrent Aspergillus fumigatus transcriptomics revealed the activation of oxidative stress responses, secondary metabolism (eg fumagillin), and iron scavenging, demonstrating reciprocal competition. Host transcriptomics revealed patient-specific immune signatures that correlated with the metabolic activity of the co-colonizers. This work provides an integrated systems-level analysis of the tri-kingdom aspergilloma ecosystem. P. aeruginosa persistence is driven by genomic plasticity and context-dependent expression of competitive pathways, shaped within a chronic inflammatory environment. These findings redefine aspergillomas as active polymicrobial consortia, establishing a framework for targeting resilient microbial communities in chronic lung disease.

Multiomics↗

PubMed2026

Arginine-substituted Mastoparan-C derivatives combat dual bacterial pathogens: in vitro mechanistic insights and in vivo efficacy in polymicrobial wounds.

UNLABELLED: The synergistic interactions in multi-pathogen infections compromise wound healing and limit therapeutic efficacy. In this study, we designed and synthesized arginine-substituted derivatives of the antimicrobial peptide Mastoparan-C (MP-C). Among them, Arg²MP-C and Arg4.11.12MP-C exhibited potent, broad-spectrum activity against both Escherichia coli and Staphylococcus aureus. Their enhanced antibacterial activity is associated with increased positive charge and optimized hydrophobicity. Mechanistically, both peptides employ a dual-target strategy, disrupting bacterial membranes and binding genomic DNA; Arg²MP-C acted most rapidly against the E. coli envelope, while Arg4.11.12MP-C caused the strongest membrane damage to S. aureus. In a murine polymicrobial wound model, Arg²MP-C treatment nearly achieved complete wound closure by day 10, significantly reduced bacterial loads, and promoted tissue regeneration. This study demonstrates that arginine engineering can yield peptides with potent, multi-mechanistic action, identifying Arg²MP-C as a promising candidate for combating polymicrobial wound infections. IMPORTANCE: Wounds infected with multiple bacterial species are notoriously difficult to treat, often leading to poor healing and limited effectiveness of existing therapies. In this study, we developed new antimicrobial peptides by introducing arginine substitutions into a natural peptide called Mastoparan-C. Two of our engineered peptides, Arg²MP-C and Arg4.11.12MP-C, showed potent activity against two common wound pathogens, Escherichia coli and Staphylococcus aureus. These peptides work through a dual mechanism: disrupting bacterial membranes and binding to bacterial DNA. In a mouse model of mixed-infection wounds, treatment with Arg²MP-C led to nearly complete wound closure by day 10, drastically reduced bacterial counts, and promoted tissue repair. Our findings highlight arginine engineering as a promising strategy to create next‑generation antimicrobial agents that can effectively combat complex polymicrobial wound infections, addressing a critical unmet need in clinical wound care.

Animals↗

PubMed2025

Pseudomonas aeruginosa phenazines dictate site-specific competitive interactions with Klebsiella pneumoniae.

Pseudomonas aeruginosa and Klebsiella pneumoniae are Gram-negative opportunistic pathogens that frequently colonize the human body and are major causes of infection. These bacteria are often co-isolated in polymicrobial urinary tract and lung infections, the latter of which is associated with increased disease severity and worse clinical outcomes. Despite their overlapping niches and clinical relevance, little is known about how these two pathogens interact and how those interactions influence human health. Given the growing recognition that microbial interactions are key drivers of disease, we investigated how P. aeruginosa and K. pneumoniae influence one another. We discovered an antagonistic interaction in which P. aeruginosa restricts the growth of K. pneumoniae. This inhibition is driven by phenazine production in P. aeruginosa, specifically the secondary metabolites pyocyanin and pyorubin, which are both necessary and sufficient to suppress K. pneumoniae growth. Using a diverse set of clinical isolates, we found that this antagonism is strain dependent. Both the susceptibility of K. pneumoniae to phenazines and the ability of P. aeruginosa to restrict K. pneumoniae growth varies between strains. Moreover, the necessity of phenazine production is specific to the site of infection. Together, these findings demonstrate that strain background and environmental context are critical determinants of pathogen interactions. Our work underscores the importance of considering these variables when investigating how microbial interactions influence infection and disease outcomes.

Journal Article↗

PubMed2026

Divergent microbial preludes to necrotising enterocolitis defined by gut phages and bacterial resistomes.

BACKGROUND: Translating microbiome correlations into robust predictive features for complex gut disorders remains elusive, partly due to oversimplified models of pathogenesis and neglect of the virome, a key player in microbial ecosystems. Necrotising enterocolitis (NEC), a devastating disease of preterm infants with no reliable clinical predictors, exemplifies this challenge. OBJECTIVE: To determine the predictive potential of the gut prophageome and polymicrobial aetiologies for NEC. DESIGN: We applied integrated metagenomic and metatranscriptomic analyses and machine learning to 1825 longitudinal stool samples from 43 preterm infants who later developed NEC and 86 gestational age-matched and birthweight-matched controls across three US hospitals. We characterised gut prophageome acquisitions and their association with clinical exposures, including antibiotics, diet and pharmacotherapies. To predict NEC risk, we integrated pre-onset prophageome, antibacterial resistome and bacteriome profiles with neonatal pathology, stratifying the cohort by disease onset timing (early: ≤40 days; late: >40 days) for separate analysis. RESULTS: NEC cases exhibited distinct viral diversity trajectories before disease onset. Early-onset NEC was best predicted by phage-bacterial interaction signatures (75% accuracy, 81% sensitivity). Metatranscriptomics revealed increased phage DNA abundance with low gene expression, suggesting a lysogenic lifestyle that may stabilise pathobionts. These phages encode metabolic genes potentially enhancing pathobiont resilience. Late-onset NEC was best predicted by antibacterial resistome profiles (83% accuracy). CONCLUSION: The gut prophageome serves as both a source of pre-symptomatic predictive signals and an active modulator of NEC pathogenesis, with distinct microbial mechanisms driving early-onset and late-onset disease. These polymicrobial etiologies inform strategies for early detection, risk stratification and the development of microbiome-targeted preventive and therapeutic interventions.

BIOMARKERS↗

PubMed2026

Cross-Kingdom Siderophores: Biosynthesis, Ecology, and Biotechnological Applications.

Microbial siderophores are high-affinity iron-binding compounds which are produced by bacteria, fungi, and actinomycetes to obtain iron and survive and interact with different species in an iron-deficient environment. While the conventional research on siderophore systems deals mainly with the study within the same taxa, modern researchers have increased their inclination toward cross-kingdom integration of siderophore behavior and their impact on host-associated environments. This can be largely attributed to differences in biosynthetic gene clusters, receptor systems, and regulatory networks, which produce distinct genotype-to-phenotype results determining microbial cooperation and competition. Current advancements in genomic research, together with omics studies like transcriptomics, proteomics, and metabolomics, have created newer insights into how siderophores function. However, the present literature evidences multiple major gaps in multi-omics data because the link between genomes and metabolomes remains weak due to inconsistent regulatory data sets and failure in identifying producer-consumer relationships in polymicrobial systems. Additionally, major constraints like molecular instability, delivery system limitations, host toxicity, limitations in upscaling, and regulatory issues delimit the use of siderophores in medical treatment, agricultural practices, and environmental biotechnology. This review aims to bridge the existing knowledge about siderophore biochemistry, biosynthesis, ecological functions, and genetic regulation across kingdoms while integrating multi-omics outlook with translational considerations. Thus, by connecting molecular mechanisms with evolutionary cross-talk, this study aims to provide a system-level framework in the world of siderophore-mediated iron uptake and therefore shapes future directions in emerging fields of microbial engineering, precision therapies, and sustainable biotechnology.

Fur regulation↗

PubMed2026

Chemo-selective proteomics in microbial systems.

SUMMARYOver the past two decades, the field of bioorthogonal chemistry has transitioned from emerging to an established cornerstone of scientific inquiry. In parallel, advances in microbial and host-microbe research have highlighted the need for functional approaches that extend beyond genomic and transcriptomic analyses to directly interrogate protein-level activity. Despite this need, proteomic strategies capable of resolving dynamic, heterogeneous, and low-abundance protein populations remain underdeveloped in microbial systems. This review highlights the convergence of chemo-selective proteomic technologies with microbial biology, focusing on bioorthogonal non-canonical amino acid tagging (BONCAT), activity- or affinity-based protein profiling, and bioorthogonal post-translational modifications, and comments on possibilities for novel applications for the use of click chemistry-based tools in the functional interrogation of microbial systems. Together, these strategies enable spatiotemporal resolution of protein synthesis, selective profiling of microbial subpopulations, and direct characterization of protein activity and regulation in complex biological contexts, including single-species cultures, host-associated environments, and polymicrobial communities. Continued development and utilization of these technologies will enable deeper mechanistic insight into how microbial systems function and respond to environmental and host-derived cues.

bioorthogonal chemistry↗

PubMed2026

Metabolic reprogramming and taxonomic drivers in bacterial vaginosis: A large-scale metagenomic meta-analysis.

OBJECTIVE: Bacterial vaginosis (BV) represents a profound ecological shift from a Lactobacillus-dominated microbiota to a diverse polymicrobial biofilm associated with adverse outcomes. While taxonomic signatures are well-documented, the functional mechanisms driving this transition remain obscured. This study elucidates the genomic potential for metabolic reprogramming and the putative "functional handover" underpinning the stability of the dysbiotic state. METHODS: A computational meta-analysis of 3557 vaginal microbiomes from diverse global cohorts was performed using the standardized MGnify pipeline. A high-resolution subset of 187 whole-genome shotgun (WGS) metagenomes was stratified to compare functional potential across demographic groups. Taxon-function interaction networks were constructed, utilizing a dual-filter statistical approach (p < 0.05 and effect size ranking), to map the shift from homeostatic maintenance to dysbiotic metabolic potential. RESULTS: BV was characterized by a fundamental shift from "maintenance" pathways to high-turnover "growth-oriented" genomic repertoires. While ABC transporter-like domains were present in healthy communities, dysbiosis was marked by a quantitative expansion and diversification of these systems alongside P-loop NTPases. Network analysis revealed a putative "functional handover": while Gardnerella serves as the adherent structural scaffold, the metabolic burden appears to be associated with secondary anaerobes, specifically BVAB1 and Sneathia, which exhibit strong genomic correlations with nutrient transport and stress response pathways. Crucially, microbiomes from women of African ancestry (Black cohort) exhibited a distinct functional profile with genomic signatures consistent with functions previously associated with resistome expansion (e.g., tetracycline/macrolide resistance), contrasting with Asian cohorts. CONCLUSION: BV is a state of metabolic reprogramming where genomic functional dominance is transferred from Lactobacillus to a cooperative network of anaerobic opportunists. Identifying BVAB1 and Sneathia as candidate metabolic engines, supported by a Gardnerella scaffold, challenges current therapeutic paradigms and highlights the potential for precision medicine targeting specific functional drivers and resistome profiles across diverse populations.

Humans↗