Co-feeding transmission facilitates strain coexistence in Borrelia burgdorferi, the Lyme disease agent

Abstract

Coexistence of multiple tick-borne pathogens or strains is common in natural hosts and can be facilitated by resource partitioning of the host species, within-host localization, or by different transmission pathways. Most vector-borne pathogens are transmitted horizontally via systemic host infection, but transmission may occur in the absence of systemic infection between two vectors feeding in close proximity, enabling pathogens to minimize competition and escape the host immune response. In a laboratory study, we demonstrated that co-feeding transmission can occur for a rapidly-cleared strain of Borrelia burgdorferi, the Lyme disease agent, between two stages of the tick vector Ixodes scapularis while feeding on their dominant host, Peromyscus leucopus. In contrast, infections rapidly became systemic for the persistently infecting strain. In a field study, we assessed opportunities for co-feeding transmission by measuring co-occurrence of two tick stages on ears of small mammals over two years at multiple sites. Finally, in a modeling study, we assessed the importance of co-feeding on R₀, the basic reproductive number. The model indicated that co-feeding increases the fitness of rapidly-cleared strains in regions with synchronous immature tick feeding. Our results are consistent with increased diversity of B. burgdorferi in areas of higher synchrony in immature feeding - such as the midwestern United States. A higher relative proportion of rapidly-cleared strains, which are less human pathogenic, would also explain lower Lyme disease incidence in this region. Finally, if co-feeding transmission also occurs on refractory hosts, it may facilitate the emergence and persistence of new pathogens with a more limited host range.

Keywords: Borrelia; Co-feeding; Coexistence; Ixodes scapularis; Lyme disease; Pathogen diversity.

Fig. 1

Transmission graph showing three distinct transmission modes between two host types: white-footed mouse (Peromyscus leucopus) infected by an Ixodes scapularis nymph (k₂₁), a larva infected by P. leucopus (k₁₂), or a larva infected by a nymph through co-feeding transmission (k₁₁). The arrows indicate these transmission modes between host types and correspond to the non-zero elements of the next-generation matrix.

Fig. 2

Borrelia burgdorferi transmission efficiency to feeding ticks infected through co-feeding (strain B348) or systemic (both strains) transmission. The proportion of I. scapularis larvae infected via co-feeding with strain B348 during the first two time periods is represented by closed circles, the proportion of strain B348 infected through systemic transmission is represented by open circles and systemic transmission in strain BBC13 is represented by open diamonds (co-feeding was negligible for BBC13, data not shown). Co-feeding transmission is represented by larvae collected from the right ear (where nymphs were placed) that tested positive for B. burgdorferi infection while left ear larvae remained uninfected. From day 17 to the end of the experiment, only systemic transmission was assumed and the proportion of all positive ticks is represented. The dotted lines represent the assumption that transmission starts at zero and returns to zero seven days after the end of the experiment (day 108).

Fig. 3

Ixodes scapularis tick feeding phenology at two sites for two years of our study: Connecticut 2014 (a), Connecticut 2015 (b), Block Island 2014 (c), and Block Island 2015 (d). Average larval and nymphal tick burdens are the average burdens on mice for each life stage. Co-feeding burdens represent the average larval burden per ear when nymphs were also present in the same ear.

Fig. 4

Estimates for the basic reproduction number R₀ for B. burgdorferi strains BBC13 (a) and B348 (b) at Connecticut and Block Island sites in 2014 and 2015 across a range of estimates for tick survival multiplied by the probability of host attachment (S_NC). We do not show co-feeding estimates for BBC13 because co-feeding was negligible for this strain. Systemic R₀ estimates are represented by open symbols, co-feeding estimates by closed symbols.

Fig. 5

Estimates for the basic reproduction number R₀ for B. burgdorferi strains BBC13 (a) and B348 (b) at Connecticut and Block Island sites in 2014 and 2015 across a range of tick feeding synchrony estimated by the proportion of early larvae (p). Systemic R₀ estimates are represented by open symbols, co-feeding (B348 only) estimates by closed symbols. The open symbols with colored filling represent the actual proportion of early larvae we found at Connecticut and Block Island in 2014 and 2015.

Fig. 6

Variation across the full range of tick feeding synchrony (p) of the elasticity values for the co-feeding transmission component k₁₁ (closed symbols) and the systemic transmission component k₁₂ (open symbols) of the next-generation matrix for strain B348.