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

Abstract

BackgroundWithin-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.ResultsThe 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0381-0) contains supplementary material, which is available to authorized users.

Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector

“…The use of 454 sequencing in the present and previous studies (24) revealed that the prevalence of multiple ospC strain infections in I. ricinus nymphs is an order of magnitude higher than what was previously shown (40). Interestingly, laboratory studies have not been able to replicate the high prevalence of multiple strain infections in nymphal ticks after letting them feed as larvae on mice coinfected with two strains (50,51). The proportion of ticks carrying multiple strain infections was 0.8% (1/129) in the study of Derdakova et al (50) and 1.5% (7/453) in the study of Devevey et al (51).…”

“…Interestingly, laboratory studies have not been able to replicate the high prevalence of multiple strain infections in nymphal ticks after letting them feed as larvae on mice coinfected with two strains (50,51). The proportion of ticks carrying multiple strain infections was 0.8% (1/129) in the study of Derdakova et al (50) and 1.5% (7/453) in the study of Devevey et al (51). Interactions between Borrelia strains in the nymphal tick are therefore 50 to 80 times more likely to occur in nature than in the lab.…”

“…2) may have important consequences for the strain-specific probability of nymphto-host transmission. Future experimental infection studies should test whether the mean infection intensity of a given strain is reduced in coinfected nymphs compared to that in nymphs infected with single strains (50,51).…”

Gut Microbiota Colonization and Transmission in the Burying Beetle Nicrophorus vespilloides throughout Development

“…2); importantly, despite limitations associated with a CFU-based approach, we observed broad overlap between the dominant bacterial species that we cultured and those identified using sequence-based approaches (e.g., Providencia, Morganella, Vagococcus, Proteus, Koukoulia, and Serratia) (33). However, with full care treatment alone, it cannot be determined if larvae require constant replenishment of the parental species for these to be maintained in the larval gut, given other research showing that gut bacteria may be transient without continuous parental provisions (24,38,39). One possibility, for example, is that the dominant bacteria from the carcass may outcompete endogenous beetle bacteria within the larval gut; this may be driven actively if the bacteria on the Nicrophorus Microbiota throughout Development Applied and Environmental Microbiology carcass are particularly good colonizers or passively since larval exposure to carcass bacteria is continuous.…”

“…While these methods of transfer can effectively vertically transmit symbionts from parent to offspring (13), the presence of an environmental component implies that young and developing insects can be simultaneously colonized by beneficial symbionts as well as environmental bacteria that can harm the host (21,22). In these cases, the establishment of the inherited microbiota will be partly dependent on the ability of inherited symbionts to competitively exclude environmental bacteria as well as the timing and manner of their acquisition (23,24). Additionally, especially for holometabolous insects that undergo a complete metamorphosis, the manner of acquisition can change markedly throughout development, at one stage occurring from the mother while at later stages occurring potentially through alternative transmission routes (12,13).…”