Polymicrobial Interactions in Chronic Infections

Chronic infections frequently involve complex communities of co-existing microorganisms whose interactions shape disease progression and therapeutic outcomes. Rather than acting in isolation, pathogens within the same niche may compete for nutrients, cooperate through metabolic exchange or signalling, and jointly modulate host responses. In cystic fibrosis airways, diabetic wounds and non-healing ulcers, biofilms comprised of bacteria and fungi display heightened tolerance to antibiotics and host immunity. Within these structured communities, chemical signals such as quorum-sensing molecules coordinate collective behaviour, while secreted factors and small-molecule exoproducts influence growth rates, virulence factor expression and resistance traits. Metabolic cross-feeding can sustain slower-growing species under nutrient limitation, whereas antagonistic interference may drive the emergence of small-colony variants with altered antimicrobial susceptibility. The dynamic balance of cooperation and competition underpins persistence, dictates pathogen succession and ultimately determines the efficacy of treatment. Recognising the ecological principles governing polymicrobial assemblies is therefore critical to developing new strategies for diagnostics, targeted therapeutics and biofilm disruption in recalcitrant infections worldwide.

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Polymicrobial Interactions in Chronic Infections publication trend

The graph below shows the total number of articles in polymicrobial interactions in chronic infections across all publications each year (not limited to Nature Index journals).

Technical terms

Biofilm: A structured community of microorganisms embedded in a self-produced extracellular matrix, exhibiting enhanced resistance to antimicrobials and host defences.

Quorum sensing: Cell-to-cell communication via small signalling molecules that coordinate gene expression and collective behaviour in microbial populations.

Cross-feeding: Metabolic cooperation where one species consumes by-products or metabolites produced by another, enabling growth under nutrient-limited conditions.

Siderophore: A low-molecular-weight iron-chelating molecule secreted by bacteria to acquire iron from the environment or host.

Exoproduct: Any secreted compound, such as toxin, enzyme or signalling molecule, that influences interactions within polymicrobial communities or with the host.

Small-colony variant (SCV): A slow-growing bacterial phenotype characterised by reduced metabolism and increased antibiotic tolerance, often emerging in chronic infections.

References

1. A bacterial pigment provides cross-species protection from H2O2- and neutrophil-mediated killing. Proceedings of the National Academy of Sciences of the United States of America (2024).
2. Competitive inhibition and mutualistic growth in co-infections: deciphering Staphylococcus aureus–Acinetobacter baumannii interaction dynamics. ISME Communications (2024).
3. Heterogeneity Governs 3D‐Cultures of Clinically Relevant Microbial Communities. Advanced Functional Materials (2023).