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The biogeography of polymicrobial infection

Nature Reviews Microbiology volume 14, pages 93–105 (2016)Cite this article

Subjects

Key Points

  • The human microbiome and invading pathogens colonize the host as spatially organized polymicrobial (multi-species or multi-strain) communities, exhibiting spatial patterning or 'biogeography' both at the macroscale (across the human body) and microscale levels (within individual infection sites).

  • Host landmarks that drive biogeography include receptors for microbial attachment, physicochemical cues of pH and oxygen, host-derived nutrients, and the immune response.

  • Specific spatial organizations that result from host–microorganism interactions include localized attachment to host surfaces, metabolically optimal positioning along physicochemical or nutritional gradients, and the enforced segregation of the microbiome from the host by the immune system.

  • Polymicrobial interactions also drive spatial organization in multispecies biofilms, generally resulting in either mixed or segregated spatial patterns, depending on the extent of cooperation or competition between community members.

  • Specific polymicrobial interactions that drive microbiogeography include intercellular attachment (within and between species), biofilm remodelling (by making or breaking down the supporting matrix), and the export of diffusible molecules that promote or suppress the growth of neighbouring cells.

  • Spatial organization and the determining community interactions can, in many cases, alter the progression of infection, in what is known as the 'biogeography of infection.'

Abstract

Microbial communities are spatially organized in both the environment and the human body. Although patterns exhibited by these communities are described by microbial biogeography, this discipline has previously only considered large-scale, global patterns. By contrast, the fine-scale positioning of a pathogen within an infection site can greatly alter its virulence potential. In this Review, we highlight the importance of considering spatial positioning in the study of polymicrobial infections and discuss targeting biogeography as a therapeutic strategy.

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Figure 1: Factors that influence microbiogeography.
Figure 2: Polymicrobial interactions contribute to microbiogeography.
Figure 3: Targeting biogeography as a therapeutic strategy.

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Acknowledgements

The authors thank members of the Whiteley laboratory for critical discussion of this manuscript. This work was supported by a US National Institutes of Health (NIH) Grant 1R01DE020100 (to M.W.) and a Human Frontier Science Program (HFSP) grant HFSP RGP0011/2014 (to S.P.B. and M.W.). M.W. is a Burroughs Wellcome Investigator in the Pathogenesis of Infectious Disease program.

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Authors and Affiliations

  1. Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, Center for Infectious Disease, The University of Texas at Austin, 1 University Station A5000, Austin, 78712, Texas, USA

    Apollo Stacy, Sophie E. Darch & Marvin Whiteley

  2. Centre for Immunity, Infection and Evolution, School of Biological Sciences, The University of Edinburgh, Edinburgh, EH9 3FL, UK

    Luke McNally

  3. School of Biology, Georgia Institute of Technology, Atlanta, 30332–0230, Georgia, USA

    Sam P. Brown

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  1. Apollo Stacy
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PowerPoint slides

Glossary

Biofilms

Surface-attached microbial communities that are encased in a matrix (for example, of polysaccharides, proteins, and/or DNA) and are often polymicrobial as well as highly resistant to antibiotic therapy and the host immune system.

Polymicrobial

Diverse in species and/or strain content.

Aggregate

A population of very few to several cells arranged in a cluster (otherwise known as a microcolony or in vivo biofilm) with many of the same properties that are observed in much larger, traditional biofilms studied in vitro.

Synergy

A positive interaction term meaning 'greater than the sum of parts'. Here we use synergy to refer to microbial interactions that shape host health (disease synergy: two or more species in combination cause more severe infection than either could when acting alone) or microbial growth (growth synergy: each species grows better in combination than when alone). Note that growth synergy often, but not always, implies disease synergy.

Metagenomics

Sequence-based analysis of the DNA recovered from microbial communities. These studies describe the genetic repertoire of a microbial community.

Metatranscriptomics

Sequence-based analysis of the mRNA recovered from microbial communities. These studies provide information regarding gene expression in a microbial community.

Microbiogeography

Although 'biogeography' refers to the distribution of species through space and time, 'microbiogeography', as defined in this Review, is the spatial organization of pathogen and commensal microbial populations at the scale of single infections.

Pellicle

The permanent layer of proteins that coat oral surfaces and provide binding sites for early colonizers of dental plaque.

Pioneer species

The first species to colonize previously disrupted ecosystems.

Fimbriae

Hair-like bacterial appendages (also known as pili) that mediate surface attachment.

Cystic fibrosis

A human genetic disorder in which a defect in a transmembrane ion channel causes the accumulation of mucus in the lungs, acting as a rich substrate for microbial growth.

Quorum sensing

Density-dependent cell–cell communication where a constitutively produced signal, once it accumulates to a threshold concentration, can trigger microbial group behaviours.

Type III secretion system

A needle-like bacterial apparatus that delivers effector proteins into host cells.

Lactoferrin

A bactericidal host protein that sequesters iron.

Mucin

A class of gel-forming proteins that give mucus its viscous property.

Neutrophils

Host immune cells that unleash a mixture of redox-active molecules, in a process known as respiratory burst, to kill microorganisms.

Aerotaxis

Chemotaxis in response to an oxygen gradient.

Cheat

In social evolution, community members that exploit, but do not contribute to, the production of 'public goods'.

Respiration

A metabolic growth process characterized by the reduction of an electron acceptor (such as oxygen or nitrate).

Intestinal crypts

The narrow spaces that lie between villi (multicellular host structures that assist in nutrient absorption) in the small and large intestine that, in a non-diseased state, are very low in microbial presence.

RegIIIγ

A host antimicrobial lectin (polysaccharide-binding protein) that targets Gram-positive bacteria.

Mucin 2

(MUC2). A primary mucin (gel-forming glycoprotein) in the mucus layers of the small and large intestine.

Co-aggregation

Intercellular binding between genetically distinct cells, often mediated by the recognition of a polysaccharide on the target cell by a cognate surface protein on the partner cell.

Mucoid

A phenotypic variant that overproduces exopolysaccharide (for example, alginate produced by Pseudomonas aeruginosa).

Autoinducer 2

A signalling molecule that is synthesized and sensed by many bacterial species.

Pyocyanin

A broad-spectrum toxin produced by Pseudomonas aeruginosa that is upregulated in response to cell-wall fragments shed by Staphylococcus aureus, underlying synergistic virulence of these species in wound infections.

Cross-feeding

The consumption of a waste product of one microorganism by another microorganism that can utilize the waste product as a nutrient source.

Cross-protection

The shielding of one microorganism by another microorganism from an external stress.

Probiotics

Microorganisms that promote host health.

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Stacy, A., McNally, L., Darch, S. et al. The biogeography of polymicrobial infection. Nat Rev Microbiol 14, 93–105 (2016). https://doi.org/10.1038/nrmicro.2015.8

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