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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

Average mouse-to-tick transmission rates (± standard error) of the primary strain. Strain A - blue circles; strain K - red squares; strain N - green triangles. The mouse-to-tick transmission rate of the secondary strain was pooled for the three strain types (purple diamonds). Inf 1 - day of inoculation with primary strain; Inf 2 - day of inoculation with secondary strain. D11, D30, D46, D65 refer to the days of blood sampling and xenodiagnosis. Sac = sacrifice for biopsy of organs (D90).
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Fig2: Average mouse-to-tick transmission rates (± standard error) of the primary strain. Strain A - blue circles; strain K - red squares; strain N - green triangles. The mouse-to-tick transmission rate of the secondary strain was pooled for the three strain types (purple diamonds). Inf 1 - day of inoculation with primary strain; Inf 2 - day of inoculation with secondary strain. D11, D30, D46, D65 refer to the days of blood sampling and xenodiagnosis. Sac = sacrifice for biopsy of organs (D90).

Mentions: The primary strain was also frequently detected in xenodiagnostic ticks that had taken their larval blood meal from the experimental mice (Figure 2) (Additional file 1: Table S2). Of the 453 ticks that tested positive for B. burgdorferi, the primary strain was present in 446. The identity of the strain affected the rate at which the strain was transmitted to feeding ticks (Δ dev = 13.63, Δdf = 2, p = 0.001), with strain K being transmitted at the highest rate followed by strain A (Figure 2). The rate of transmission of the primary strain to feeding ticks varied among the four xenodiagnostic time points (Δdev = 11.64, Δdf = 3, p = 0.009), although the pattern of temporal variation differed significantly among strains (Δdev = 33.67, Δdf = 6, p < 0.001). While strain K was transmitted to feeding ticks at a consistently high rate throughout the experiment, the transmission rate of strain A decreased over time, and the transmission rate of strain N peaked in the middle time points.Figure 2


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)

Average mouse-to-tick transmission rates (± standard error) of the primary strain. Strain A - blue circles; strain K - red squares; strain N - green triangles. The mouse-to-tick transmission rate of the secondary strain was pooled for the three strain types (purple diamonds). Inf 1 - day of inoculation with primary strain; Inf 2 - day of inoculation with secondary strain. D11, D30, D46, D65 refer to the days of blood sampling and xenodiagnosis. Sac = sacrifice for biopsy of organs (D90).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Average mouse-to-tick transmission rates (± standard error) of the primary strain. Strain A - blue circles; strain K - red squares; strain N - green triangles. The mouse-to-tick transmission rate of the secondary strain was pooled for the three strain types (purple diamonds). Inf 1 - day of inoculation with primary strain; Inf 2 - day of inoculation with secondary strain. D11, D30, D46, D65 refer to the days of blood sampling and xenodiagnosis. Sac = sacrifice for biopsy of organs (D90).
Mentions: The primary strain was also frequently detected in xenodiagnostic ticks that had taken their larval blood meal from the experimental mice (Figure 2) (Additional file 1: Table S2). Of the 453 ticks that tested positive for B. burgdorferi, the primary strain was present in 446. The identity of the strain affected the rate at which the strain was transmitted to feeding ticks (Δ dev = 13.63, Δdf = 2, p = 0.001), with strain K being transmitted at the highest rate followed by strain A (Figure 2). The rate of transmission of the primary strain to feeding ticks varied among the four xenodiagnostic time points (Δdev = 11.64, Δdf = 3, p = 0.009), although the pattern of temporal variation differed significantly among strains (Δdev = 33.67, Δdf = 6, p < 0.001). While strain K was transmitted to feeding ticks at a consistently high rate throughout the experiment, the transmission rate of strain A decreased over time, and the transmission rate of strain N peaked in the middle time points.Figure 2

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