Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Feb;69(2):147-161.
doi: 10.1099/jmm.0.001134. Epub 2020 Jan 21.

Harnessing bacterial interactions to manage infections: a review on the opportunistic pathogen Pseudomonas aeruginosa as a case example

Chiara Rezzoagli  1 , Elisa T Granato  2   3 , Rolf Kümmerli  1
Affiliations
Review

Harnessing bacterial interactions to manage infections: a review on the opportunistic pathogen Pseudomonas aeruginosa as a case example

Chiara Rezzoagli et al. J Med Microbiol. 2020 Feb.

Abstract

During infections, bacterial pathogens can engage in a variety of interactions with each other, ranging from the cooperative sharing of resources to deadly warfare. This is especially relevant in opportunistic infections, where different strains and species often co-infect the same patient and interact in the host. Here, we review the relevance of these social interactions during opportunistic infections using the human pathogen Pseudomonas aeruginosa as a case example. In particular, we discuss different types of pathogen-pathogen interactions, involving both cooperation and competition, and elaborate on how they impact virulence in multi-strain and multi-species infections. We then review evolutionary dynamics within pathogen populations during chronic infections. We particuarly discuss how local adaptation through niche separation, evolutionary successions and antagonistic co-evolution between pathogens can alter virulence and the damage inflicted on the host. Finally, we outline how studying bacterial social dynamics could be used to manage infections. We show that a deeper appreciation of bacterial evolution and ecology in the clinical context is important for understanding microbial infections and can inspire novel treatment strategies.

Keywords: Pseudomonas aeruginosa; alternative treatments; ecology and evolution; infections; polymicrobial infections; social interactions; sociomicrobiology.

PubMed Disclaimer

Conflict of interest statement

Competing Interests

The authors have no competing interests to declare.

Figures

Figure 1
Figure 1. Social interactions during P. aeruginosa monoinfections.
Patients can be infected with either a single P. aeruginosa clone or a set of genetically diverse strains. Depending on the composition of the bacterial population at the infection site, cooperative or competitive interactions can occur. (A) Cells can cooperate through the secretion of metabolites (green hexagons, e.g. enzymes, quorum sensing molecules, siderophores) which can be shared as public good among cells. (B) Another form of cooperation is the secretion of an extracellular matrix (light green area) to form biofilms to adhere to tissues and surfaces. Biofilms offer collective protection against external threats such as antibiotics. (C) Cooperation through public good sharing can be exploited by non-producing cells (in yellow) that do not contribute to the production of shared goods but exploit molecules produced by others. (D) Genetically diverse strains can compete against each other by producing narrow-range toxins (green and blue lightnings) that aim to kill closely related competitors.
Figure 2
Figure 2. Social interactions between P. aeruginosa and other species.
During infections, P. aeruginosa is often in contact with other species (yellow cocci), which can be other pathogens or members of the local microbiome. Different types of interactions can occur between species. (A) Bacteria can compete with each other over limited host resources (light brown circles), such as iron. (B) Species can engage in interference competition and secrete broad-spectrum toxins (green lightnings) to kill other species or to activate the host immune system (blue cells), which then specifically _targets the competitor (orange lightning). (C) Bacteria can regulate their gene expression by sensing competing microbial species via the non-specific AI-2 quorum sensing molecules (yellow stars). Upon AI-2 sensing, P. aeruginosa typically upregulates the secretion of virulence factors (green hexagons). (D) Interactions between species can promote changes in bacterial lifestyle, such as the induction of biofilm production, or the formation of small colony variants (SCV).
Figure 3
Figure 3. Adaptations and evolutionary dynamics in infections.
Once an infection is established, bacteria can evolve in the host in response to different selection pressures. P. aeruginosa can evolve in response to (A) the host environment, (B) intraspecific social dynamics, or (C) the presence of a competing species. (A) An initially clonal strain (grey cell) infecting different regions of the same organ can adapt to local host conditions and result in independently evolving populations (coloured cells). (B) During long-term and chronic infections, P. aeruginosa populations can undergo a succession of evolutionary changes. Here we depict a population of producers of a shared virulence factor (green cells and hexagons), which is invaded by cheating non-producers (yellow cells). Once cooperators are extinct, new mutations (blue cells), showing improved performance after the collapse of cooperation, are selectively favoured. (C) Evolutionary change in one co-infecting species (transition from green to blue cells) can select for adaptations in the competing species (transition from yellow to orange cells, resulting in antagonistic co-evolution between species.
Figure 4
Figure 4. Strategies to manipulate social interactions to manage infections.
Several approaches have been suggested to manipulate social interactions between strains and species in order to steer infections towards lower virulence and to improve treatment response. (A) The cooperative sharing of virulence factors (green hexagon) can increase virulence during single species infections, while their exploitation by non-producers (yellow cells) can reduce pathogenicity. Thus, one treatment approach (scenario A1) suggests to induce strain mixing to favour the spread of cheating on shared molecules to reduce virulence. Alternatively (scenario A2), engineered cheaters (yellow cell with DNA) could be used as a vehicle to introduce medically beneficial alleles into a population, which allow improved treatment of the infection after cheater invasion. (B) Antibiotics have two main limitations: they strongly select for resistant clones and they perform poorly against biofilms. One approach is to _target shared virulence factors with antivirulence compounds (yellow semi-circles, scenario B1), a treatment that should exert weaker selection for resistance than antibiotics. Another strategy is to either inhibit biofilm formation or to disrupt mature biofilms to improve susceptibility to antibiotics (scenario B2). (C) Similarily to the antivirulence approach, molecules quenching inter-specific quorum-sensing signals (brown semi-circles) can reduce virulence (scenario C1). Finally, pathogens could be beaten at their own game through the use of bacteriocins from competing species (blue lightning symbols, scenario C2).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alizon S, de Roode JC, Michalakis Y. Multiple infections and the evolution of virulence. Ecol Lett. 2013;16:556–567. doi: 10.1111/ele.12076. - DOI - PubMed
    1. Allen RC, Popat R, Diggle SP, Brown SP. _targeting virulence: can we make evolution-proof drugs? Nat Rev Microbiol. 2014;12:300–308. doi: 10.1038/nrmicro3232. - DOI - PubMed
    1. Amin AN, Deruelle D. Healthcare-associated infections, infection control and the potential of new antibiotics in development in the USA. Future Microbiol. 2015;10:1049–1062. doi: 10.2217/fmb.15.33. - DOI - PubMed
    1. Andersen SB, Ghoul M, Marvig RL, Lee ZBin, Molin S, Johansen HK, Griffin AS. Privatisation rescues function following loss of cooperation. eLife. 2018;7:e38594. doi: 10.7554/eLife.38594. - DOI - PMC - PubMed
    1. Andersen SB, Marvig RL, Molin S, Krogh Johansen H, Griffin AS. Long-term social dynamics drive loss of function in pathogenic bacteria. Proc Natl Acad Sci. 2015;112:10756–10761. doi: 10.1073/pnas.1508324112. - DOI - PMC - PubMed

MeSH terms

  NODES
INTERN 1
twitter 2