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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.

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Related in: MedlinePlus

The primary strain induced a strong strain-specific adaptive immune response. The secondary strain did not alter immune response. Each panel shows one of nine co-infection treatments. Antibody profiles are similar within columns, which share the primary strain, but differ among rows, which share the secondary strain. This pattern indicates that the primary strain dominated the antibody response and that antibody profiles differed among primary strains (Additional file 1: Table S6 and S7). Arrows indicate the timing of the primary and secondary inoculation. Shown are the mean antibody titers (± S.E.) for total IgG (black diamond), anti-flagellin IgG (white diamond), anti-OspCA IgG (blue circle), anti-OspCK (red square), and anti-OspCN (green triangle). To facilitate viewing, absolute differences in scale among the five antibody variables were removed by standardizing them to z-scores (mean = 0, stdev = 1).
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Fig3: The primary strain induced a strong strain-specific adaptive immune response. The secondary strain did not alter immune response. Each panel shows one of nine co-infection treatments. Antibody profiles are similar within columns, which share the primary strain, but differ among rows, which share the secondary strain. This pattern indicates that the primary strain dominated the antibody response and that antibody profiles differed among primary strains (Additional file 1: Table S6 and S7). Arrows indicate the timing of the primary and secondary inoculation. Shown are the mean antibody titers (± S.E.) for total IgG (black diamond), anti-flagellin IgG (white diamond), anti-OspCA IgG (blue circle), anti-OspCK (red square), and anti-OspCN (green triangle). To facilitate viewing, absolute differences in scale among the five antibody variables were removed by standardizing them to z-scores (mean = 0, stdev = 1).

Mentions: The primary strain induced a strong immune response as measured by total immunoglobulin G (IgG) production as well as a strong specific immune response against flagellin and against the OspC genotype expressed by the primary strain (Figure 3). The anti-OspC response induced against the primary strain had low cross-reactivity with the OspC antigen of the secondary strains. In other words, the anti-OspC antibodies induced by strain A infection had low affinity for OspC type K nor type N proteins and vice versa. The inoculation of the secondary strain did not affect the total IgG level, the anti-Fla response, nor the specific anti-OspC response targeting either the primary or the secondary strain, even in the mice with conclusive evidence of infection by the secondary strain.Figure 3


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)

The primary strain induced a strong strain-specific adaptive immune response. The secondary strain did not alter immune response. Each panel shows one of nine co-infection treatments. Antibody profiles are similar within columns, which share the primary strain, but differ among rows, which share the secondary strain. This pattern indicates that the primary strain dominated the antibody response and that antibody profiles differed among primary strains (Additional file 1: Table S6 and S7). Arrows indicate the timing of the primary and secondary inoculation. Shown are the mean antibody titers (± S.E.) for total IgG (black diamond), anti-flagellin IgG (white diamond), anti-OspCA IgG (blue circle), anti-OspCK (red square), and anti-OspCN (green triangle). To facilitate viewing, absolute differences in scale among the five antibody variables were removed by standardizing them to z-scores (mean = 0, stdev = 1).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: The primary strain induced a strong strain-specific adaptive immune response. The secondary strain did not alter immune response. Each panel shows one of nine co-infection treatments. Antibody profiles are similar within columns, which share the primary strain, but differ among rows, which share the secondary strain. This pattern indicates that the primary strain dominated the antibody response and that antibody profiles differed among primary strains (Additional file 1: Table S6 and S7). Arrows indicate the timing of the primary and secondary inoculation. Shown are the mean antibody titers (± S.E.) for total IgG (black diamond), anti-flagellin IgG (white diamond), anti-OspCA IgG (blue circle), anti-OspCK (red square), and anti-OspCN (green triangle). To facilitate viewing, absolute differences in scale among the five antibody variables were removed by standardizing them to z-scores (mean = 0, stdev = 1).
Mentions: The primary strain induced a strong immune response as measured by total immunoglobulin G (IgG) production as well as a strong specific immune response against flagellin and against the OspC genotype expressed by the primary strain (Figure 3). The anti-OspC response induced against the primary strain had low cross-reactivity with the OspC antigen of the secondary strains. In other words, the anti-OspC antibodies induced by strain A infection had low affinity for OspC type K nor type N proteins and vice versa. The inoculation of the secondary strain did not affect the total IgG level, the anti-Fla response, nor the specific anti-OspC response targeting either the primary or the secondary strain, even in the mice with conclusive evidence of infection by the secondary strain.Figure 3

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