Microbial Connections: The Bizarre World of Microbe Matchmaking

Microbial Connections: The Bizarre World of Microbe Matchmaking

By Tallita Tavares

“Happiness is only real when shared.” - Christopher McCandless

“No man is an island.” - John Donne

Quotes like these have proven to be true throughout the years, especially after the recent COVID-19 pandemic, where most people suffered the effects of being isolated. More than that, social life has helped our ancestors to survive and was the key to the success of early humans. However, when we consider microorganisms, is it possible to talk about the social life of microbes?

When we think about microorganisms, we usually think of tremendously packed groups. Could those groups have persisted without any kind of interaction? Moreover, wouldn’t they have perished without some kind of communication? Even if we imagine the most chaotic traffic jam, it couldn’t progress without any type of communication, even if it consists of insistent honking and swearing. And, if noise and cursing work, what else wouldn’t, right?

The hermit microbe paradox

It used to be assumed that bacteria and other microorganisms lived relatively independent unicellular lives, without cooperative behaviors commonly studied in mammals, birds, and insects. Paradoxically, most microbes are social enough to live in dense communities, but not so social to the point of abandoning their unicellularity. For example, bacteria can reach abundances of 1 x 10⁸ cells/g in dry soil and 5 x 10⁵ cells/mL in the oceans, while viruses reach 5 x 10⁹ particles/g or 1 x 10¹¹ particles/mL respectively in the same places. In such huge groups, where the concept of individuality is practically unthinkable, any form of cooperation, communication, or synchronization can be beneficial.

Indeed, considering the cornucopia of different microorganisms - bacteria, archaea, fungi, protozoa, microalgae, and viruses, belonging to the three domains of life in nearly every niche on Earth, they mostly form complex interactive networks within the ecosystem rather than exist as a single cell. The interactions occur with the same and different species or even with entirely diverse genera, families, or even domains. As a matter of fact, forming such relationships is essential for the successful establishment and maintenance in various environments. Individuals communicate and cooperate to perform activities, such as dispersal, foraging, construction of biofilms, reproduction, chemical warfare, and signaling. For example, 6-10% of all genes in the bacterium Pseudomonas aeruginosa are controlled by cell-cell signaling systems. So, more than a matter of deep longing for physical contact and fulfillment, it’s a question of survival!

Being in a relationship

Now, in the world of microbial matchmaking, how do they connect? While poets, philosophers, seers, and psychologists have been trying to decipher the secret language of love, microbiologists have made amazing advances in our understanding of microbial social behaviors. Those behaviors can take part in various symbiotic relationships, facilitating commensal, mutualistic, and synergistic relationships, as well as parasitic, competitive, and antagonistic interactions. All those occur through the transfer of molecular and genetic information, which means that the basic unit of microbial interaction is gene expression. Based on it, in response to biotic and abiotic stimuli, secondary metabolites, signaling molecules, signal transduction signals, and other genetic elements are produced, detected, or inhibited.

Through these means, microbes enter into a myriad of connections. To the unsuspecting spectator, they could seem rather simple when compared to the complicated human relationship statuses. However, through the magnifying glass (or at least through the microscope's lenses), microbes are not limited to a single type of interaction at each time. Their responses are transient and influenced by the chemical and/or physical environment, resulting in highly complex microbial communities.

Some of those relationships can be very similar to some love connections, seemingly as complex as some of them. For instance, mutualism between some microbes can be similar to a monogamous marriage, in which this type of symbiosis (relationship in which organisms live together) is needed for survival in a specific habitat the pair inhabit. Ecologically speaking, this connection benefits both partners. A classic inter-domain marriage is the relationship between Rhizobium spp. and legume plants (family Fabaceae or Leguminosae), in which bacteria colonize the roots to fix nitrogen in exchange for nutrients. Another not so known example is the symbiosis between the archaeon Ignicoccus hospitalis and Nanoarchaeum equitans. In this marriage, N. equitans directly attaches to the outer membrane of I. hospitalis and obligatorily depends on Ignococcus because of its highly reduced genome that lacks genes for essential biosynthetic pathways. Other arrangements also work in the microbial world. This is the case of synergism, when microbes interact in non-monogamous relationships. For example, in a syntrophic archaea-bacteria consortium, gram-negative bacteria Methanobacillus omelianskii can live together with a methanogenic archaeon, and they can syntrophically convert ethanol to acetate and methane. There are other examples like this, including polyamorous relationships, such as Thermoanaerobacter, Desulfotomaculum, and Pelotomaculum synergism under thermophilic conditions.

Other relationships are more similar to friendships, where one partner can be benefited and the other is not harmed nor improved. A great example is formed by Nitrosomonas and Nitrobacter, chemoautotrophic organisms found in soil and water, which transform ammonium to nitrite (Nitrosomonas) and, then, nitrite to nitrate (Nitrobacter). This process, known as nitrification, is important because it can affect plant growth beneficially. Viruses also can be good friends. Some viruses known as phages are the most abundant microorganism in the biosphere (~ 4.8 x 10³¹ particles), being present in all areas. They are natural killers of bacteria and can help in controlling the size of bacterial communities.

Moreover, they are well-known vectors of horizontal gene transfer, interfering with bacterial diversity, virulence, evolvability, and even shaping the stability of whole ecosystems. One just has to be careful not to enter into a toxic friendship.

Well, it’s not always rainbows and butterflies. Some relationships are rather difficult, such as the cases of parasitism, competition, and antagonism. Competition for resources like nutrients and space is a strong reason to use some fight tactics. Antibiotics are the best-known examples, being produced by some microorganisms to antagonize the growth of others. Another interesting example is the mycoparasite Trichoderma, a saprophytic fungi with fast mycelial growth, rapid absorption of nutrients, and strong adaptability to the environment. These features allow them to outcompete other fungi in the root of a plant, which has resulted in their use as a biological control tool against fungi and nematode plant infections.

Biofilm nostro, Casa nostra

Some relationships are so successful that they evolve and become famiglias (which means family in Italian). In the microbial world, biofilms are like the Corleone family, with one of the most widely distributed and successful modes of life. It is an aggregate of microbial cells embedded in a self-produced extracellular matrix of polymeric substances. The biofilm formation begins with some bacteria adhering to a surface or to each other. Then they proliferate and produce an extracellular matrix to form microcolonies, where molecular communication among cells is facilitated. As cells continue to proliferate, the biofilm gets a tridimensional conformation in which many species of high cell density (ranging from 10⁸ to 10¹¹ cells/g wet weight) are organized amid cellular signals, extracellular DNA, RNA, and proteins. Such live structure maintain an equilibrium through growth and dispersal. The strategy of living in a biofilm guarantees some beneficial metabolic interactions between different species. For instance, the essential process of nitrification can take place in a biofilm, where ammonia-oxidizing bacteria convert ammonium into nitrite, which is then oxidized to nitrate by nitrite-oxidizing bacteria. Many forms of cooperation can be involved in the establishment of a biofilm, such as cooperative production of extracellular matrix, sharing of public goods such as biosurfactants and metabolites, regulation of localized cell death, and even some specialization analogous to how some castes develop in social insects. Paraphrasing Don Vito Corleone in The Godfather: The strength of a biofilm, like the strength of an army, lies in its aggregation with each other.

The ancient molecular language

It’s well known that conversation is the bond to any companionship. Scholars even claim that one of the many factors in the downfall of the Roman Empire was the inadequacy of the methods of communication for the size the Empire attained. Cell-to-cell communication is also ultimately important for bacteria. Many of them use a density-dependent system called Quorum Sensing (QS), which is based on the synthesis and perception of low molecular weight molecules. Those molecules, called autoinducers (AI), diffuse over the cytoplasmic membrane or are actively transported and detected by specific receptors. When the density of a bacterial population increases, the concentration of signaling molecules passes a threshold (“quorum”) and causes the synthesis of more autoinducers and activation of receptors. This induces a synchronized production of certain types of molecules by a population. Thus, such chemical language coordinates cell-density-related behaviors, such as colonization, virulence, pathogenicity, and biofilm formation as well.

The first description of QS was on the bioluminescent marine bacterium Vibrio fischeri, which lives in a symbiotic association with the Hawaiian bobtail squid Euprymna scolopes. At high densities, the bacteria activate bioluminescence through QS and support the squid in hiding from predators. The luminescence mimics down-welling moonlight and starlight so that the squid does not cast a shadow that could be detected by a predator.

QS allows bacteria to communicate also with different bacteria species as well as with their hosts. This was observed in the relationship between the marine bacteria V. anguillarum and the green seaweed Enteromorpha. In this example, bacteria release molecules that attract zoospores (the motile reproductive stage of the seaweed), which then settle and develop in response.

Quorum sensing is considered an almost universal communication as many autoinducers are synthesized and recognized by many species in manifold and adaptable isoforms. QS is involved in intra- and inter-domain communication leading to cooperative and competitive interactions, which highlights the importance of this fundamental communication system.

Sometimes, toxic relationships arise. There are some microorganisms that do not produce QS but are sensitive to the toxicity of their signals. Those organisms interfere with the QS communication by signal blockage or prevention of signal reception, which is called Quorum Quenching (QQ).  QQ is considered a natural mechanism evolved either by organisms regulating QS-mediated behaviors, cleaning QS signals, or in competition with QS-signal-producing organisms. Interestingly, research on QQ can be applied to developing antibacterial and antidisease strategies that target pathogens and biofilm-forming bacteria in medicine, agronomy, and industry. Those treatments can be alternative or complementary approaches to ineffective antibiotics. One of those studies proposes the use of macerate or oil garlic as a QS inhibitor against P. aeruginosa, which is resistant to many antibiotics (Rasmussen et al., 2005). Bad breath can really spoil a date, indeed!

Communication is gold

Lynn Margulis was the first to recognize the importance of bacteria in the evolution of higher organisms. Since then, more and more studies have shown that we can give far more credit to the oldest inhabitants of this pale blue dot. They can teach by example some lessons that some of the best philosophers have been trying to teach for centuries: communication is gold!

And for the lovebirds, I give a useful hint: perhaps you can trust the chemical language more than the spoken one!

If you want to know more about the social life of microorganisms, refer to:

Weiland-Bräuer, N. Friends or Foes—Microbial Interactions in Nature. Biology 2021, 10, 496. https://doi.org/10.3390/biology10060496

West, S. A., Diggle, S. P., Buckling, A., Gardner, A., Griffin, A. S. The Social Lives of Microbes. Annual Review of Ecology, Evolution, and Systematics 2007, 38:1, 53-77. https://doi.org/10.1146/annurev.ecolsys.38.091206.095740

Rasmussen, T.B., Bjarnsholt, T., Skindersoe, M.E., Hentzer, M., Kristoffersen, P., Köte, M., Nielsen, J., Eberl, L., Givskov, M. Screening for Quorum-Sensing Inhibitors (QSI) by Use of a Novel Genetic System, the QSI Selector. Journal of Bacteriology 2005, 187, 1799–1814. https://doi.org/10.1128/jb.187.5.1799-1814.2005