Intraspecies heterogeneity in microbial interactions

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Microbial interactions are increasingly recognized as an integral part of microbial physiology. Cell–cell communication mediated by quorum sensing and metabolite exchange is a formative element of microbial interactions. However, loss-of-function mutations in quorum-sensing components are common across diverse species. Furthermore, quorum sensing is modulated by small molecules and environmental conditions that may be altered in the presence of other microbial species. Recent evidence highlights how strain heterogeneity impacts microbial interactions. There is great potential for microbial interactions to act as selective pressures that influence the emergence of common mutations in quorum-sensing genes across the bacterial and fungal domains.

Introduction

Microbial cells are hardly ever alone. Because microbes almost always live adjacent to kin or different microbial species, microbial interactions are intimately linked with microbial viability, activity and community structure. In fact, it has been proposed that obligate mutualism between microbes is a reason why many remain unculturable [1]. The continuous presence of neighbors necessitates control over inter-species and intra-species interactions. Quorum sensing is one important mechanism that governs both interaction types. Although the regulatory components vary in composition and specific gene targets, commonalities exist across species (Figure 1a). For example, quorum sensing frequently controls the production of catabolic enzymes, small inhibitory molecules, and biofilm related factors via signal-responsive transcription factors. Alongside its use in intraspecies signaling, quorum-sensing systems respond to the signals produced by other species in the local vicinity. Despite the importance of quorum-sensing pathways for intra-species and inter-species relationships, loss-of-function mutations in quorum-sensing genes are frequently observed in bacteria and fungi (Figure 1b). At first this appears to present a paradox: since microbial neighbors are present for most microbial life, why might loss-of-function mutations in key mediators of microbial interactions be beneficial? Recent studies provide novel insight into this phenomenon. In this review, we will summarize frequent loss-of-function mutations in quorum sensing-related genes and discuss recent factors that influence the fitness of quorum-sensing mutants. We will review how heterogeneity in quorum sensing affects microbe–microbe interactions and discuss how microbial interactions may influence the rates at which these mutations arise.

Section snippets

Loss-of-function mutations in cell–cell communication genes are common across diverse species

Numerous studies suggest that the quorum-sensing systems in both gram-positive and gram-negative bacteria are frequently under selection. The agr quorum-sensing locus of Staphylococcus aureus (agrBDCA) exists in several types based on specific single nucleotide polymorphisms in agrC and agrD encoding a histidine sensor kinase and the precursor peptide of its cognate signal respectively, and loss-of-function mutations have been identified in isolates from persistent and chronic infections [2,3].

Small molecules modulate quorum sensing during microbial interactions

Signal and receptor promiscuity allow for ‘eavesdropping,’ or communication between species and across domains of life. This may provide useful information about the local environment, but the ability of other species to modulate quorum sensing regulation may also make it less useful or even a liability. An investigation into the extent of signal promiscuity in the well-studied quorum sensing receptors of P. aeruginosa (LasR, RhlR, and QscR), Vibrio fischeri (LuxR), Chromobacterim violaceum

What are the consequences of quorum sensing heterogeneity on microbial interactions?

Strains with deficiencies in quorum sensing can have unexpected intra-species and inter-species interactions compared to their wild-type counterparts. Because the hapR mutant is often used to study V. cholerae biofilm formation due to its strong preference for biofilm over dispersal, the biofilm behaviors of hapR loss-of-function mutants are perhaps better understood than their HapR + counterparts. By investigating the wild-type V. cholerae biofilm development over time, it is apparent that hapR

Do microbial interactions affect the selection for quorum sensing mutations?

In addition to altering composition and community function through mutualism, direct combat, resource competition, and cross-signaling, interactions between organisms can alter evolutionary trajectories [35]. Nearby microbial life can alter many abiotic factors like pH, redox, carbon/nitrogen availability, and metal content—all of which are potential selective pressures. In a cellular automation model investigating a mutualistic interspecies interaction, a mutation with a mildly

Other common genetic changes may influence and be influenced by microbial interactions

Like quorum-sensing molecules, metabolite exchange mediates microbial interactions. Often the metabolite pool is a direct result of microbial metabolism mediated by bi-directional or uni-directional exchange. Such exchanges can lead to the emergence of metabolic feedback loops that can drive antagonism or mutual growth. While other interactions increase respiration [41,42], P. aeruginosa antagonizes C. albicans via an antifungal phenazine [43] that inhibits respiration to promote C. albicans

Conclusions

The diversity in functional genotype, especially with respect to quorum sensing, makes it important to consider the specific physiology of the interacting strains and genotypes when studying an interaction. Given the probability that a microbe is in the presence of others (either non-identical kin or distinct species), the impact of microbial interactions on evolution may be extensive. We posit that microbe–microbe interactions have the potential to drive and prevent selection of many of the

Conflict of interest statement

Nothing declared.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

Acknowledgements

Research reported in this publication was supported by grants from the National Institutes of Health to D.A.H. from the Cystic Fibrosis Foundation (HOGAN19G0), STANTO19R0 from the Cystic Fibrosis Foundation, and NIDDKP30-DK117469 (Dartmouth Cystic Fibrosis Research Center). Support for D.L.M came in part from NIH/NIAIDT32AI007519 (D.L.M).

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