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  • Review Article
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Developing animal models for polymicrobial diseases

Nature Reviews Microbiology volume 2, pages 552–568 (2004)Cite this article

Key Points

  • Although polymicrobial diseases are not a new concept for microbiologists, they are experiencing a resurgence of interest owing to the development of suitable animal models and new molecular techniques that allow these diseases to be studied effectively. This broad review provides an excellent introduction to this fascinating topic.

  • Examples are included of each type of polymicrobial disease and the animal models that are used to study these diseases are discussed. In many instances, schematics for the animal model are presented.

  • Viral co-infections including bovine viral diarrhoeal viruses, porcine reproductive and respiratory syndrome, mixed hepatitis virus infections and HIV co-infection with hepatitis virus are discussed, together with attempts to model these diseases in animals.

  • Viral and bacterial co-infections are reviewed with a special focus on otitis media and the rodent models that have been used to probe this important childhood illness.

  • Of the polybacterial diseases, periodontitis is one of the best understood and a clinically relevant rodent model is now available. This model, and the role of biofilm formation in periodontitis are examined.

  • Fungal infections of humans are often referred to as 'opportunistic' but in fact these infections are often fungal co-infections with viruses such as HIV and fungal mixed co-infections. The roles of these infections in disease and the rodent models used to study them are discussed.

  • Parasite co-infections are thought to have a role in the severity of malaria and the severity of Lyme arthritis. These diseases and attempts to model them are evaluated.

  • Finally, co-infections that are associated with virus-induced immunosuppression are discussed, together with their animal models.

Abstract

Polymicrobial diseases involve two or more microorganisms that act synergistically, or in succession, to mediate complex disease processes. Although polymicrobial diseases in animals and humans can be caused by similar organisms, these diseases are often also caused by organisms from different kingdoms, genera, species, strains, substrains and even by phenotypic variants of a single species. Animal models are often required to understand the mechanisms of pathogenesis, and to develop therapies and prevention regimes. However, reproducing polymicrobial diseases of humans in animal hosts presents significant challenges.

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Figure 1: Human polymicrobial diseases.
Figure 2: A chinchilla experimental model for otitis media.
Figure 3: A model of oral biofilm formation.
Figure 4: Animal models for periodontal disease.
Figure 5: A mouse model for candidiasis.
Figure 6: Animal model for Lyme disease and human granulocytic ehrlichiosis (HGE) co-infection.

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Acknowledgements

The author would like to thank J. Neelans for help with manuscript preparation.

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Authors and Affiliations

  1. Department of Pediatrics, Center for Microbial Pathogenesis, Columbus Children's Research Institute, The Ohio State University College of Medicine & Public Health, 700 Children's Drive, Columbus, 43205-2696, Ohio, USA

    Lauren O. Bakaletz

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DATABASES

Entrez

Bordetella bronchiseptica

Escherichia coli

Haemophilus somnus

hepatitis A virus

hepatitis B virus

hepatitis D virus

hepatitis G virus

herpes simplex virus type 2

HIV-1

HTLV-2

Neisseria meningitidis

Pasteurella multocida

Plasmodium falciparum

porcine circovirus 2

porcine parvovirus

PRRS virus

Pseudomonas aeruginosa

Streptococcus pneumoniae

Infectious Disease Information

chickenpox

Lyme disease

otitis media

FURTHER INFORMATION

Biofilm movies

ASM Microbial Communities report

ASM conference on polymicrobial diseases

Lauren O. Bakaletz's laboratory

Glossary

VIRAL INTERFERENCE

One virus suppresses the replication of another.

HELPER VIRUS

A virus in a mixed infection that provides a complementing function so that a co-infecting defective virus can replicate.

CHALLENGED

Inoculated with an infectious agent.

SEROCONVERSION

The development of antibodies in serum as a result of infection or immunization.

BACTERIAL CPG DNA

Immunostimulatory bacterial DNA that is enriched in unmethylated CPG dinucleotides.

TURBINATE

A small curved bone along the lateral wall of the nasal passage.

SUBSTRAINS

Genetic variants of a single strain as determined by techniques such as multilocus enzyme electrophoresis or random amplified polymorphic DNA analysis.

BYSTANDER ANTIGENS

Factors that can activate T cells without their specific antigen — without triggering through their T-cell receptor.

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Bakaletz, L. Developing animal models for polymicrobial diseases. Nat Rev Microbiol 2, 552–568 (2004). https://doi.org/10.1038/nrmicro928

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