Limits...
First arrived takes all: inhibitory priority effects dominate competition between co-infecting Borrelia burgdorferi strains.

Devevey G, Dang T, Graves CJ, Murray S, Brisson D - BMC Microbiol. (2015)

Bottom Line: Hence, the data do not support a major role of the immune response in the observed priority effect.The strong inhibitory priority effect is a dominant mechanism underlying competition for transmission between coinfecting B. burgdorferi strains, most likely through resource exploitation.The observed priority effect could shape bacterial diversity in nature, with consequences in epidemiology and evolution of the disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Leidy Laboratories, University of Pennsylvania, Hamilton Walk, Philadelphia, PA, 19104, USA. godefroy.devevey@ed.ac.uk.

ABSTRACT

Background: Within-host microbial communities and interactions among microbes are increasingly recognized as important factors influencing host health and pathogen transmission. The microbial community associated with a host is indeed influenced by a complex network of direct and indirect interactions between the host and the lineages of microbes it harbors, but the mechanisms are rarely established. We investigated the within-host interactions among strains of Borrelia burgdorferi, the causative agent of Lyme disease, using experimental infections in mice. We used a fully crossed-design with three distinct strains, each group of hosts receiving two sequential inoculations. We used data from these experimental infections to assess the effect of coinfection on bacterial dissemination and fitness (by measuring the transmission of bacteria to xenodiagnostic ticks) as well as the effect of coinfection on host immune response compared to single infection.

Results: The infection and transmission data strongly indicate a competitive interaction among B. burgdorferi strains within a host in which the order of appearance of the strain is the main determinant of the competitive outcome. This pattern is well described by the classic priority effect in the ecological literature. In all cases, the primary strain a mouse was infected with had an absolute fitness advantage primarily since it was transmitted an order of magnitude more than the secondary strain. The mechanism of exclusion of the secondary strain is an inhibition of the colonization of mouse tissues, even though 29% of mice showed some evidence of infection by secondary strain. Contrary to expectation, the strong and specific adaptive immune response evoked against the primary strain was not followed by production of immunoglobulins after the inoculation of the secondary strain, neither against strain-specific antigen nor against antigens common to all strains. Hence, the data do not support a major role of the immune response in the observed priority effect.

Conclusion: The strong inhibitory priority effect is a dominant mechanism underlying competition for transmission between coinfecting B. burgdorferi strains, most likely through resource exploitation. The observed priority effect could shape bacterial diversity in nature, with consequences in epidemiology and evolution of the disease.

Show MeSH

Related in: MedlinePlus

Infection in mouse tissues at Day 90 was dominated by the primary strain. Few tissue samples tested positive for the secondary strains. Ear tissue was less frequently infected than the other organs. n = 4 mice per group except in groups KK and NN where n = 3 mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4359528&req=5

Fig1: Infection in mouse tissues at Day 90 was dominated by the primary strain. Few tissue samples tested positive for the secondary strains. Ear tissue was less frequently infected than the other organs. n = 4 mice per group except in groups KK and NN where n = 3 mice.

Mentions: We used three Borrelia burgdorferi sensu stricto isolates that differed at their ospC locus to experimentally infect 36 three-month old female C3H/HeJ mice (Charles River). The B. burgdorferi isolates 97–064 (strain A), 97–010 (strain K), and 931222 (strain N) were obtained through the Center for Disease Control as part of the standard patient care, which did not require ethical approval. Each strain (passage 3–5) was grown in BSK-II complete medium [30] at 35°C, washed three times with phosphate buffer saline (PBS) and concentrations were equalized after cell counting by hemocytometer, prior to subcutaneous injection of 5*104 cells in 200 μl of PBS. Mice were randomly assigned to a co-infection treatment (4 mice per treatment) after acclimation to the animal facility for one week. Mice were randomly paired and kept two per cage. Two individuals in groups KK and NN died for unknown reasons during the 90-day course of the experiment. Mice in the homologous co-infection treatment groups were infected with same strain on days 0 and day 35 (d35) of the experiment (A-A, K-K, N-N). Mice in the heterologous co-infection treatments groups were infected by two different strains during the experiment (A-K, K-A; A-N, N-A; K-N, N-K). At day 90, mice were sacrificed by CO2 inhalation and blood was collected by cardiac puncture. Tissue samples from the ear, the bladder, the heart, and the mammary glands were extracted and frozen for subsequent analysis of tissue tropism of each strain (Figure 1). The animal experimentation protocol was approved by the University of Pennsylvania IACUC (801614).Figure 1


First arrived takes all: inhibitory priority effects dominate competition between co-infecting Borrelia burgdorferi strains.

Devevey G, Dang T, Graves CJ, Murray S, Brisson D - BMC Microbiol. (2015)

Infection in mouse tissues at Day 90 was dominated by the primary strain. Few tissue samples tested positive for the secondary strains. Ear tissue was less frequently infected than the other organs. n = 4 mice per group except in groups KK and NN where n = 3 mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359528&req=5

Fig1: Infection in mouse tissues at Day 90 was dominated by the primary strain. Few tissue samples tested positive for the secondary strains. Ear tissue was less frequently infected than the other organs. n = 4 mice per group except in groups KK and NN where n = 3 mice.
Mentions: We used three Borrelia burgdorferi sensu stricto isolates that differed at their ospC locus to experimentally infect 36 three-month old female C3H/HeJ mice (Charles River). The B. burgdorferi isolates 97–064 (strain A), 97–010 (strain K), and 931222 (strain N) were obtained through the Center for Disease Control as part of the standard patient care, which did not require ethical approval. Each strain (passage 3–5) was grown in BSK-II complete medium [30] at 35°C, washed three times with phosphate buffer saline (PBS) and concentrations were equalized after cell counting by hemocytometer, prior to subcutaneous injection of 5*104 cells in 200 μl of PBS. Mice were randomly assigned to a co-infection treatment (4 mice per treatment) after acclimation to the animal facility for one week. Mice were randomly paired and kept two per cage. Two individuals in groups KK and NN died for unknown reasons during the 90-day course of the experiment. Mice in the homologous co-infection treatment groups were infected with same strain on days 0 and day 35 (d35) of the experiment (A-A, K-K, N-N). Mice in the heterologous co-infection treatments groups were infected by two different strains during the experiment (A-K, K-A; A-N, N-A; K-N, N-K). At day 90, mice were sacrificed by CO2 inhalation and blood was collected by cardiac puncture. Tissue samples from the ear, the bladder, the heart, and the mammary glands were extracted and frozen for subsequent analysis of tissue tropism of each strain (Figure 1). The animal experimentation protocol was approved by the University of Pennsylvania IACUC (801614).Figure 1

Bottom Line: Hence, the data do not support a major role of the immune response in the observed priority effect.The strong inhibitory priority effect is a dominant mechanism underlying competition for transmission between coinfecting B. burgdorferi strains, most likely through resource exploitation.The observed priority effect could shape bacterial diversity in nature, with consequences in epidemiology and evolution of the disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Leidy Laboratories, University of Pennsylvania, Hamilton Walk, Philadelphia, PA, 19104, USA. godefroy.devevey@ed.ac.uk.

ABSTRACT

Background: Within-host microbial communities and interactions among microbes are increasingly recognized as important factors influencing host health and pathogen transmission. The microbial community associated with a host is indeed influenced by a complex network of direct and indirect interactions between the host and the lineages of microbes it harbors, but the mechanisms are rarely established. We investigated the within-host interactions among strains of Borrelia burgdorferi, the causative agent of Lyme disease, using experimental infections in mice. We used a fully crossed-design with three distinct strains, each group of hosts receiving two sequential inoculations. We used data from these experimental infections to assess the effect of coinfection on bacterial dissemination and fitness (by measuring the transmission of bacteria to xenodiagnostic ticks) as well as the effect of coinfection on host immune response compared to single infection.

Results: The infection and transmission data strongly indicate a competitive interaction among B. burgdorferi strains within a host in which the order of appearance of the strain is the main determinant of the competitive outcome. This pattern is well described by the classic priority effect in the ecological literature. In all cases, the primary strain a mouse was infected with had an absolute fitness advantage primarily since it was transmitted an order of magnitude more than the secondary strain. The mechanism of exclusion of the secondary strain is an inhibition of the colonization of mouse tissues, even though 29% of mice showed some evidence of infection by secondary strain. Contrary to expectation, the strong and specific adaptive immune response evoked against the primary strain was not followed by production of immunoglobulins after the inoculation of the secondary strain, neither against strain-specific antigen nor against antigens common to all strains. Hence, the data do not support a major role of the immune response in the observed priority effect.

Conclusion: The strong inhibitory priority effect is a dominant mechanism underlying competition for transmission between coinfecting B. burgdorferi strains, most likely through resource exploitation. The observed priority effect could shape bacterial diversity in nature, with consequences in epidemiology and evolution of the disease.

Show MeSH
Related in: MedlinePlus