Population Bottlenecks during the Infectious Cycle of the Lyme Disease Spirochete Borrelia burgdorferi (original) (raw)
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Multiple independent transmission cycles of a tick-borne pathogen within a local host community
Many pathogens are maintained by multiple host species and involve multiple strains with potentially di erent phenotypic characteristics. Disentangling transmission patterns in such systems is often challenging, yet investigating how di erent host species contribute to transmission is crucial to properly assess and manage disease risk. We aim to reveal transmission cycles of bacteria within the Borrelia burgdorferi species complex, which include Lyme disease agents. We characterized Borrelia genotypes found in 488 infected Ixodes ricinus nymphs collected in the Sénart Forest located near Paris (France). These genotypes were compared to those observed in three sympatric species of small mammals and network analyses reveal four independent transmission cycles. Statistical modelling shows that two cycles involving chipmunks, an introduced species, and non-sampled host species such as birds, are responsible for the majority of tick infections. In contrast, the cycle involving native bank voles only accounts for a small proportion of infected ticks. Genotypes associated with the two primary transmission cycles were isolated from Lyme disease patients, con rming the epidemiological threat posed by these strains. Our work demonstrates that combining high-throughput sequence typing with networks tools and statistical modeling is a promising approach for characterizing transmission cycles of multi-host pathogens in complex ecological settings.
Interactions Between Ticks and Lyme Disease Spirochetes
Current Issues in Molecular Biology, 2022
Borrelia burgdorferi sensu lato causes Lyme borreliosis in a variety of animals and humans. These atypical bacterial pathogens are maintained in a complex enzootic life cycle that primarily involves a vertebrate host and Ixodes spp. ticks. In the Northeastern United States, I. scapularis is the main vector, while wild rodents serve as the mammalian reservoir host. As B. burgdorferi is transmitted only by I. scapularis and closely related ticks, the spirochete-tick interactions are thought to be highly specific. Various borrelial and arthropod proteins that directly or indirectly contribute to the natural cycle of B. burgdorferi infection have been identified. Discrete molecular interactions between spirochetes and tick components also have been discovered, which often play critical roles in pathogen persistence and transmission by the arthropod vector. This review will focus on the past discoveries and future challenges that are relevant to our understanding of the molecular interactions between B. burgdorferi and Ixodes ticks. This information will not only impact scientific advancements in the research of ticktransmitted infections but will also contribute to the development of novel preventive measures that interfere with the B. burgdorferi life cycle. caister.com/cimb 113 Curr. Issues Mol. Biol. Vol. 42 Curr. Issues Mol. Biol. 42: 113-144. caister.com/cimb Interactions Between Ticks and Spirochetes Pal et al. scapularis are highly specific. Limited studies have shed light on these complex pathogen-tick interactions (Munderloh and Kurtti, 1995; Fikrig and Narasimhan, 2006); a recent review summarizes our most current state of knowledge about the interactions between B. burgdorferi and I. scapularis ticks (Kurokawa et al., 2020). Vector competence, which depends on genetic determinants influencing the vector's ability to transmit a pathogen, also shapes interactions involving the tick, pathogen, and host (de la Fuente et al., 2017). With the advent of genetic tools for creating Borrelia mutants (Samuels et al., 2018) (see also Radolf and Samuels, 2021) and the current availability of the I. scapularis genome (Gulia-Nuss et al., 2016; Miller et al., 2018), investigators will have increasingly robust tools for studying Borrelia-tick interactions, both during the arthropod phase of the spirochete life cycle and at the interface with the mammalian host. A few borrelial proteins already have been demonstrated as prerequisites for spirochete-vector interactions, particularly with receptors in select tick organs, such as the gut or salivary gland (
PLOS Pathogens, 2018
Lyme disease in humans is caused by several genospecies of the Borrelia burgdorferi sensu lato (s.l.) complex of spirochetal bacteria, including B. burgdorferi, B. afzelii and B. garinii. These bacteria exist in nature as obligate parasites in an enzootic cycle between small vertebrate hosts and Ixodid tick vectors, with humans representing incidental hosts. During the natural enzootic cycle, infected ticks in endemic areas feed not only upon naïve hosts, but also upon seropositive infected hosts. In the current study, we considered this environmental parameter and assessed the impact of the immune status of the blood-meal host on the phenotype of the Lyme disease spirochete within the tick vector. We found that blood from a seropositive host profoundly attenuates the infectivity (>10 4 fold) of homologous spirochetes within the tick vector without killing them. This dramatic neutralization of vector-borne spirochetes was not observed, however, when ticks and blood-meal hosts carried heterologous B. burgdorferi s.l. strains, or when mice lacking humoral immunity replaced wild-type mice as blood-meal hosts in similar experiments. Mechanistically, serum-mediated neutralization does not block induction of host-adapted OspC+ spirochetes during tick feeding, nor require tick midgut components. Significantly, this study demonstrates that strain-specific antibodies elicited by B. burgdorferi s.l. infection neutralize homologous bacteria within feeding ticks, before the Lyme disease spirochetes enter a host. The blood meal ingested from an infected host thereby prevents super-infection by homologous spirochetes, while facilitating transmission of heterologous B. burgdorferi s.l. strains. This finding suggests that Lyme disease spirochete diversity is stably maintained within endemic populations in local geographic regions through frequency-dependent selection of rare alleles of dominant polymorphic surface antigens.
Microbiome, 2022
Background: Ixodes scapularis is the predominant tick vector of Borrelia burgdorferi, the agent of Lyme disease, in the USA. Molecular interactions between the tick and B. burgdorferi orchestrate the migration of spirochetes from the midgut to the salivary glands-critical steps that precede transmission to the vertebrate host. Over the last decade, research efforts have invoked a potential role for the tick microbiome in modulating tick-pathogen interactions. Results: Using multiple strategies to perturb the microbiome composition of B. burgdorferi-infected nymphal ticks, we observe that changes in the microbiome composition do not significantly influence B. burgdorferi migration from the midgut, invasion of salivary glands, or transmission to the murine host. We also show that within 24 and 48 h of the onset of tick feeding, B. burgdorferi spirochetes are within the peritrophic matrix and epithelial cells of the midgut in preparation for exit from the midgut. Conclusions: This study highlights two aspects of tick-spirochete interactions: (1) environmental bacteria associated with the tick do not influence spirochete transmission to the mammalian host and (2) the spirochete may utilize an intracellular exit route during migration from the midgut to the salivary glands, a strategy that may allow the spirochete to distance itself from microbiota in the midgut lumen effectively. This may explain in part, the inability of environment-acquired midgut microbiota to significantly influence spirochete transmission. Unraveling a molecular understanding of this exit strategy will be critical to gain new insights into the biology of the spirochete and the tick.
Host dispersal shapes the population structure of a tick‐borne bacterial pathogen
Molecular Ecology, 2019
Jaenson, & Bergstrom, 1995), which may greatly impact the distribution and population structure of ticks and their associated pathogens. The life cycle of tick-borne pathogens is complex and their evolutionary ecology is shaped by the interactions with vertebrate hosts and tick vectors (Kurtenbach et al., 2006). This study focused on the ecology and genetic diversity of B. burgdorferi s.l. as a model to investigate the drivers of the population structure and to understand the role of host-associated dispersal on the evolution of tick-borne pathogens. This represents a consequential question in the ecology and evolution of any pathogen. Borrelia burgdorferi s.l. is a bacterial complex of over 20 known genospecies, including the etiologic agents of Lyme borreliosis (Casjens et al., 2011; Margos et al., 2015), whose main vectors are ticks of the genus Ixodes (Eisen & Lane, 2002). These bacteria are widespread in Europe, Asia and
Parasites & vectors, 2017
The population dynamics of vector-borne pathogens inside the arthropod vector can have important consequences for vector-to-host transmission. Tick-borne spirochete bacteria of the Borrelia burgdorferi (sensu lato) species complex cause Lyme borreliosis in humans and spend long periods of time (>12 months) in their Ixodes tick vectors. To date, few studies have investigated the dynamics of Borrelia spirochete populations in unfed Ixodes nymphal ticks. Larval ticks from our laboratory colony of I. ricinus were experimentally infected with B. afzelii, and killed at 1 month and 4 months after the larva-to-nymph moult. The spirochete load was also compared between engorged larval ticks and unfed nymphs (from the same cohort) and between unfed nymphs and unfed adult ticks (from the same cohort). The spirochete load of B. afzelii in each tick was estimated using qPCR. The mean spirochete load in the 1-month-old nymphs (~14,000 spirochetes) was seven times higher than the 4-month-old ny...
Live imaging reveals a biphasic mode of dissemination of Borrelia burgdorferi within ticks
Journal of Clinical Investigation, 2009
Lyme disease is caused by transmission of the spirochete Borrelia burgdorferi from ticks to humans. Although much is known about B. burgdorferi replication, the routes and mechanisms by which it disseminates within the tick remain unclear. To better understand this process, we imaged live, infectious B. burgdorferi expressing a stably integrated, constitutively expressed GFP reporter. Using isolated tick midguts and salivary glands, we observed B. burgdorferi progress through the feeding tick via what we believe to be a novel, biphasic mode of dissemination. In the first phase, replicating spirochetes, positioned at varying depths throughout the midgut at the onset of feeding, formed networks of nonmotile organisms that advanced toward the basolateral surface of the epithelium while adhering to differentiating, hypertrophying, and detaching epithelial cells. In the second phase of dissemination, the nonmotile spirochetes transitioned into motile organisms that penetrated the basement membrane and entered the hemocoel, then migrated to and entered the salivary glands. We designated the first phase of dissemination "adherence-mediated migration" and provided evidence that it involves the inhibition of spirochete motility by one or more diffusible factors elaborated by the feeding tick midgut. Our studies, which we believe are the first to relate the transmission dynamics of spirochetes to the complex morphological and developmental changes that the midgut and salivary glands undergo during engorgement, challenge the conventional viewpoint that dissemination of Lyme disease-causing spirochetes within ticks is exclusively motility driven. Conflict of interest: Justin D. Radolf has significant equity holdings in Johnson & Johnson, Pfizer, and General Electric and receives royalties from Biokit SA.
Journal of Theoretical Biology, 2003
Lyme disease and Tick-Borne Encephalitis (TBE) are two emergent tick-borne diseases transmitted by the widely distributed European tick Ixodes ricinus. The life cycle of the vector and the number of hosts involved requires the development of complex models which consider different routes of pathogen transmission including those occurring between ticks that co-feed on the same host. Hence, we consider here a general model for tick-borne infections. We assumed ticks feed on two types of host species, one competent for viraemic transmission of infection, the second incompetent but included a third transmission route through nonviraemic transmission between ticks co-feeding on the same host. Since a blood meal lasts for several days these routes could lead to interesting nonlinearities in transmission rates, which may have important effects.
Species Co-Occurrence Patterns among Lyme Borreliosis Pathogens in the Tick Vector Ixodes ricinus
Applied and Environmental Microbiology, 2013
Mixed infections have important consequences for the ecology and evolution of host-parasite interactions. In vector-borne diseases, interactions between pathogens occur in both the vertebrate host and the arthropod vector. Spirochete bacteria belonging to the Borrelia burgdorferi sensu lato genospecies complex are transmitted by Ixodes ticks and cause Lyme borreliosis in humans. In Europe, there is a high diversity of Borrelia pathogens, and the main tick vector, Ixodes ricinus, is often infected with multiple Borrelia genospecies. In the present study, we characterized the pairwise interactions between five B. burgdorferi sensu lato genospecies in a large data set of I. ricinus ticks collected from the same field site in Switzerland. We measured two types of pairwise interactions: (i) co-occurrence, whether double infections occurred more or less often than expected, and (ii) spirochete load additivity, whether the total spirochete load in double infections was greater or less than the sum of the single infections. Mixed infections of Borrelia genospecies specialized on different vertebrate reservoir hosts occurred less frequently than expected (negative co-occurrence) and had joint spirochete loads that were lower than the additive expectation (inhibition). In contrast, mixed infections of genospecies that share the same reservoir hosts were more common than expected (positive cooccurrence) and had joint spirochete loads that were similar to or greater than the additive expectation (facilitation). Our study suggests that the vertebrate host plays an important role in structuring the community of B. burgdorferi sensu lato genospecies inside the tick vector.