Intraspecies heterogeneity in microbial interactions
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).
References (66)
- et al.
Bacterial unculturability and the formation of intercellular metabolic networks
Trends Microbiol
(2017) - et al.
Candida albicans quorum-sensing molecule farnesol modulates staphyloxanthin production and activates the thiol-based oxidative-stress response in Staphylococcus aureus
Virulence
(2019) - et al.
Mutation of agr is associated with the adaptation of Staphylococcus aureus to the host during chronic osteomyelitis
Front Cell Infect Microbiol
(2018) - et al.
Genome plasticity of agr-defective Staphylococcus aureus during clinical infection
Infect Immun
(2018) - et al.
Gene loss and acquisition in lineages of Pseudomonas aeruginosa evolving in cystic fibrosis patient airways
mBio
(2020) - et al.
Rapid genetic and phenotypic changes in Pseudomonas aeruginosa clinical strains during ventilator-associated pneumonia
Sci Rep
(2019) - et al.
Comparative genomics of clinical strains of Pseudomonas aeruginosa strains isolated from different geographic sites
Sci Rep
(2018) - et al.
The outlier Pseudomonas aeruginosa strain ATCC 9027 harbors a defective LasR quorum-sensing transcriptional regulator
FEMS Microbiol Lett
(2020) - et al.
Genetic and phenotypic diversity of quorum-sensing systems in clinical and environmental isolates of Vibrio cholerae
Infect Immun
(2006) - et al.
Finding of Agr phase variants in Staphylococcus aureus
mBio
(2019)
Evolution of the Pseudomonas aeruginosa quorum-sensing hierarchy
Proc Natl Acad Sci U S A
Disappearance of quorum sensing in Burkholderia glumae during experimental evolution
Microb Ecol
RhlR-regulated acyl-homoserine lactone quorum sensing in a cystic fibrosis isolate of Pseudomonas aeruginosa
mBio
Enhanced production of farnesol by Candida albicans treated with four azoles
Antimicrob Agents Chemother
Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol
Appl Environ Microbiol
Secretion of E,E-farnesol and biofilm formation in eight different Candida species
Antimicrob Agents Chemother
In vitro and in vivo effect of exogenous farnesol exposure against Candida auris
Front Microbiol
Abrogation of pathogenic attributes in drug resistant Candida auris strains by farnesol
PLoS One
Hemizygosity enables a mutational transition governing fungal virulence and commensalism
Cell Host Microbe
Candida albicans Zn cluster transcription factors Tac1 and Znc1 are activated by farnesol to upregulate a transcriptional program including the multidrug efflux pump CDR1
Antimicrob Agents Chemother
Progress in and promise of bacterial quorum sensing research
Nature
Quorum sensing signal selectivity and the potential for interspecies cross talk
mBio
Effect of co-inhabiting coagulase negative Staphylococci on S. aureus agr quorum sensing, host factor binding, and biofilm formation
Front Microbiol
Fluconazole resistance in Candida albicans is induced by Pseudomonas aeruginosa quorum sensing
Sci Rep
Inhibition of the pqsABCDE and pqsH in the pqs quorum sensing system and related virulence factors of the Pseudomonas aeruginosa PAO1 strain by farnesol
Int Biodeterior Biodegrad
The intragenus and interspecies quorum-sensing autoinducers exert distinct control over Vibrio cholerae biofilm formation and dispersal
PLoS Biol
Candida albicans impacts Staphylococcus aureus alpha-toxin production via extracellular alkalinization
mSphere
Candida albicans augments Staphylococcus aureus virulence by engaging the Staphylococcal agr quorum sensing system
mBio
Remasking of Candida albicans β-Glucan in response to environmental pH is regulated by quorum sensing
mBio
Intraspecies signaling between common variants of Pseudomonas aeruginosa increases production of quorum-sensing-controlled virulence factors
mBio
Nutrient availability as a mechanism for selection of antibiotic tolerant Pseudomonas aeruginosa within the CF airway
PLoS Pathog
Pseudomonas aeruginosa lasR mutant fitness in microoxia is supported by an Anr-regulated oxygen-binding hemerythrin
Proc Natl Acad Sci U S A
Pseudomonas aeruginosa ethanol oxidation by AdhA in low-oxygen environments
J Bacteriol
Cited by (15)
Social network of filamentous Sphaerotilus during activated sludge bulking: Identifying the roles of signaling molecules and verifying a novel control strategy
2023, Chemical Engineering JournalCitation Excerpt :N-Acyl homoserine lactones (AHLs) are the most well-known QS “language”, they have been shown to regulate a variety of bacterial behaviors, such as extracellular polymeric substance (EPS) secretion, biofilm formation, morphological development, etc. [23–25]. Despite AHLs had varied structures due to a variable acyl side chain, unique signal-activated receptors have been shown to respond to structurally similar signals [26,27]. It is well-known that signal receptor LuxR is unique to Gram-negative bacteria and homodimerizes and binds adjacent QS signals to activate the transcription of target genes [22,26,27].
Integrating variation in bacterial-fungal co-occurrence network with soil carbon dynamics
2024, Journal of Applied Ecology