Interactions between environmental factors shape the fitness and traits of individual microorganisms
Environmental factors often combine non additively to shape the phenotypes and fitness of microorganisms (Kaplan et al., 2008; Okano et al., 2020; Wood et al., 2012). Interactions between environmental factors on microbial growth and phenotypes have been a major focus of microbiology since the early days of the discipline (Blaiseau and Holmes, 2021). Among the most iconic examples we find diauxic growth, whereby microorganisms consume nutrients in succession, rather than simultaneously. The effect of a nutrient on the growth of a microorganism will thus be masked by the presence of another nutrient whose hierarchy in the diauxic choice is higher (Aidelberg et al., 2014; Bajic and Sanchez, 2020). This interaction between nutrients is akin to the phenomenon of dominance in genetics, an interaction whose result is the masking of the phenotypic effect of an allele by the presence of another (dominant) allele in a diploid organism.
Diauxic growth is implemented by genetic networks that respond to the presence of more than one input nutrient by activating the metabolic pathways required to metabolize just one of them, but not the others. Beyond the specific example of diauxie, many microbial gene-regulatory networks integrate multiple environmental inputs (Espinar et al., 2013; Kaplan et al., 2008), and bacterial promoters commonly contain binding sites for multiple different transcription factors (Bintu et al., 2005; Rydenfelt et al., 2014). The combinatorial nature of gene regulatory networks and their ability to integrate multiple environmental signals provides a basis for the emergence of complex interactions between environmental factors.
Interactions between environmental factors do not need to have a gene regulatory basis. An example are the well-characterized interactions between antibiotics. It has been shown that antibiotics targeting different cellular processes often act synergistically (Cacace et al., 2023; Yeh et al., 2006), whereby the detrimental effect of an antibiotic is higher than expected when a second antibiotic is present too (Yeh et al., 2009). Systematic screens of interactions between antibiotics have found that they are pervasive in both Gram positive and Gram negative bacterial species (Wood et al., 2012), and they can exhibit substantial complexity (Lázár et al., 2022). Antibiotics can also interact with physical environmental factors, and their very presence in the medium can alter the optimal growth temperature of bacteria, and modulate the effect of stressful temperatures (Cruz-Loya et al., 2021). The idea that two or more stressors may act non-additively is an old concept in microbial ecology (for a recent example see (Smith et al., 2023)), which in fact extends well beyond the realm of microorganisms (Côté et al., 2016).
Interactions between environmental factors may affect biotechnologically significant traits. For instance, Skonieczny & Yargeau examined the combined effect of the initial pH and initial glucose concentration on the rate of H2 produced by populations of the bacteriumClostridium beijerinckii(Skonieczny and Yargeau, 2009). At low initial glucose concentrations, H2 production peaked at pH=6.1. Yet, when higher initial concentrations of glucose were provided, the peak shifted to higher values of pH, close to 6.5. In other words, an increase in glucose concentration changes the response of H2 production to pH, and this affects the optimal pH in the culture. This particular case exemplifies the potential significance of interactions between environmental factors in biotechnology, and we did not have to dig deeply to find it. Most environmental factors exhibit a non-additive effect even when they are the only ones being changed. Take for instance the example of Temperature. Microbial Temperature response curves are not only non-linear but also non-monotonic. A 2oC increase in Temperature will have a positive effect in the carbon use efficiency of microorganisms below their optimal temperature (Smith et al., 2021), but a detrimental effect when it takes place above that point. This well-known example illustrates the many challenges of predicting the effect of the environment on organismal traits, a challenge that extends to the community level.