Our understanding of microorganisms and their impact/importance in life on earth has come a long way since Antonie van Leeuwenhoek first observed single celled microbes under the microscope. For many years microorganisms were considered “simple” cells with small genomes and basic cell machinery. In early microbiology, these simple cells were studied in simple contexts – pure culture under highly artificial laboratory growth conditions. In recent times, advances in the field of microbiology have revealed that microbes possess a complex physiology and a genome that is constantly evolving to survive the different conditions that they encounter outside of the highly controlled environment of a microbiology lab. We now know that these organisms can colonize habitats that are inhospitable for any other life form, they not only exist as single cells but can also aggregate into a biofilm in which they can communicate with neighboring microbes and establish interactions, and that these complex communities of microbes impact every aspect of our lives. With all the knowledge we have now about the lives of microorganisms one might think there is nothing left to be discovered. That is not true at all! In fact, the majority of microorganisms in existence have never been cultured in the lab and even the best studied microorganisms possess numerous genes with completely unknown functions. 

Recently, microbiologists have been making attempts to mimic more realistic scenarios by studying microbial communities containing multiple species 1. These studies have revealed the importance of microbial interactions in driving the physiological responses of microbes. In fact, these co-culture studies have revealed that sometimes a microbe requires the presence of a community in order to be able to be grown in a laboratory setting because these “helper microbes” can provide nutrients and/or alleviate stressors for the unculturable microbes 2-4. Therefore, we hypothesized that similar types of cooperation might be happening in our bodies during chronic infections, which are known to contain multiple microbial species. When we surveyed the literature, we were able to find numerous examples in which microorganisms seemed to lose their competitive strategies during  infection 5-9 and examples in which microbes seemed to synergize to exacerbate disease 10,11. Due to the harsh nature of sites of infection which includes host-mediated limitation of certain essential nutrients, microbial competition would intuitively be rampant. So, what are the possible reasons that cooperation might evolve in this environment? We hypothesize that cooperative interactions can reduce individual biosynthesis cost by promoting a division of labor for resource production and potentially increase virulence of the pathogens as a community by enabling neighboring microbes to exploit the unique suite of defensive molecules that each microbe possesses for survival in the presence of an active immune response (as shown in the figure). The evolutionary race of pathogenic microbes against host defense strategies might play a role in unifying competing microbial species and rendering them resistant and more virulent as a community than as individual species.

Reference

1. Mihai, M. M. et al. Microbial biofilms: impact on the pathogenesis of periodontitis, cystic fibrosis, chronic wounds and medical device-related infections. Curr Top Med Chem 15, 1552-1576 (2015).
2. Stewart, E. J. Growing unculturable bacteria. J Bacteriol 194, 4151-4160, doi:10.1128/JB.00345-12 (2012).
3. Hoffman, L. R. et al. Nutrient availability as a mechanism for selection of antibiotic tolerant Pseudomonas aeruginosa within the CF airway. PLoS Pathog 6, e1000712, doi:10.1371/journal.ppat.1000712 (2010).
4. Dalton, T. et al. An in vivo polymicrobial biofilm wound infection model to study interspecies interactions. PLoS One 6, e27317, doi:10.1371/journal.pone.0027317 (2011).
5. Limoli, D. H. et al. Pseudomonas aeruginosa Alginate Overproduction Promotes Coexistence with Staphylococcus aureus in a Model of Cystic Fibrosis Respiratory Infection. MBio 8, doi:10.1128/mBio.00186-17 (2017).
6. Frydenlund Michelsen, C. et al. Evolution of metabolic divergence in Pseudomonas aeruginosa during long-term infection facilitates a proto-cooperative interspecies interaction. ISME J 10, 1323-1336, doi:10.1038/ismej.2015.220 (2016).
7. Kummerli, R., van den Berg, P., Griffin, A. S., West, S. A. & Gardner, A. Repression of competition favours cooperation: experimental evidence from bacteria. J Evol Biol 23, 699-706, doi:10.1111/j.1420-9101.2010.01936.x (2010).
8. Wakeman, C. A. et al. The innate immune protein calprotectin promotes Pseudomonas aeruginosa and Staphylococcus aureus interaction. Nat Commun 7, 11951, doi:10.1038/ncomms11951 (2016).
9. Smith, A. C. et al. Albumin Inhibits Pseudomonas aeruginosa Quorum Sensing and Alters Polymicrobial Interactions. Infect Immun 85, doi:10.1128/IAI.00116-17 (2017).
10. Cohen, T. S. et al. Staphylococcus aureus alpha toxin potentiates opportunistic bacterial lung infections. Sci Transl Med 8, 329ra331, doi:10.1126/scitranslmed.aad9922 (2016).
11. Pastar, I. et al. Interactions of methicillin resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in polymicrobial wound infection. PLoS One 8, e56846, doi:10.1371/journal.pone.0056846 (2013).

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