In this study an Asian house shrew B. elizabethae
strain (Sm6145vi) infected laboratory mice, a demonstration of cross-order host switching by the bacteria (from Order Soricomorpha to Order Rodentia). This is to some extent an unusual finding as bartonella bacteria generally only infect and produce bacteremias in hosts taxonomically close to their natural reservoir hosts (28
). The ability of this strain to host switch across mammalian orders may make it more likely to undergo zoonotic transmission to humans (27
). Though this B. elizabethae
strain was isolated from a shrew, its close phylogenetic relatedness to rat isolates of B. elizabethae
in the same location means it is likely a spillover from rats to sympatric shrews in Vietnam. Therefore, unlike some other bartonellae this strain seems to have an inherent capacity to infect diverse hosts (29
). However, bacteremia occurred only in mice inoculated with high doses of B. elizabethae
cfu), and it remains uncertain how many bartonella bacteria are required to establish infection under natural conditions.
has been reported as the causative agent of several cases of human illness (6
), and serologic evidence of human infection with the bacterium has been reported from Thailand (10
). Still, the zoonotic potential of this bacterium is not well understood. Since B. elizabethae
, and strains phylogenetically close to B. elizabethae
have been found in numerous commensal small mammal populations in Asia (15
), an understanding of the risk to humans for acquiring infections from these hosts is desirable. Given that the level of host specificity of an infectious agent is generally considered a predictor for the likelihood that the agent can switch hosts, and potentially cause illness in those hosts, our findings help define the zoonotic potential of this bacteria (27
Previously, B. elizabethae
isolated from a human endocarditis patient (the type strain) was evaluated for its ability to infect several different rodent species, among them R. norvegicus
, a natural reservoir host for the bacteria (22
). In that study the bacteria failed to infect Wistar rats (R. norvegicus
), cotton rats (Sigmodon hispidus
), BALB/c (M. musculus
), and white-footed deer mice (Peromyscus leucopus
), though inoculated doses were as high as 107
). It remains unknown whether the bacteria had undergone adaptation to the human host resulting in a high level of host specificity, or whether the isolate's passage history might have influenced the outcome (34
). An additional unanswered question was whether related isolates from natural reservoirs would also display a narrow host range, or a host specific phenotype.
In contrast to those findings, we observed susceptibility of three stocks of M. musculus
(SW, BALB/c, and C57BL/6) to infection with B. elizabethae
Sm6145vi at doses of 105
bacteria. Mice developed bacteremia levels potentially high enough to infect ectoparasites such as fleas feeding on a host during the course of bacteremia (35
). The bacteremia levels observed in our incidental host mouse model may be sufficient to promote some secondary infections of susceptible hosts, especially if high enough levels of bacterial exposure exist in terms of transmissible contacts between animals.
Subjective differences in bacteremia levels between mice inoculated at the same dose may be due to individual host response, with respect to the particular mouse stock (). Likewise, differences between bacteremia levels of infected mice of the three stocks could be explained by individual mouse responses, stock differences, or dose differences (, SW mice infected at two different doses). With such small numbers of bacteremic mice it is difficult to speculate or draw conclusions about the bacteremia levels.
Bacteremias of several months duration or more are commonly observed in natural reservoir hosts infected with their co-adapted bartonellae (5
). The bacteremia duration of mice in our study is shorter than that observed during such natural host infections, but is consistent with bacteremia kinetics of laboratory mice experimentally infected with non-homologous host source bartonellae (37
). Truncations in bacteremia duration are likely due to the bacteria not being optimally adapted to laboratory mice, and are probably characteristic of non-natural host infections (32
Similar, small proportions of mice of each stock used in this study were susceptible to infection and developed bacteremias following inoculation of B. elizabethae
strain Sm6145vi. The differing genetic backgrounds among the three stocks did not appear to affect susceptibility of mice to infection, at least not with the dose range assayed. It is possible that inoculation of larger group sizes would reveal more apparent differences between stocks. We did not attempt to assess for differential response to infection for the three mouse stocks at different exposure doses, as the number of bacteremic mice in each dose group was low. It would be difficult to assign a biologically significant interpretation to such slight differences in infection rates and level and duration of bacteremia without knowing that the observed differences are relevant to the transmission dynamics of the bacteria. Bacteremia duration in infected hosts almost undoubtedly affects the transmission likelihood of the bacteria. Simply put, long bacteremias increase the size of the temporal window for potentially transmissible contacts to occur between infected hosts and susceptibles, or for arthropod vectors to acquire the agent (27
). Likewise high bacteremia levels can influence the probability that contacts with infected hosts result in bacterial transmission or arthropod vectors become infected following ingestion of infectious blood (27
). However, to reasonably extrapolate our laboratory based findings to the natural transmission cycle of B. elizabethae
, additional studies need to be done to define the transmission dynamics of the bacteria in its normal hosts.
Further evaluations of B. elizabethae
Sm6145vi could yield more information about this bacterium's host switching ability, adaptive capacity, and zoonotic potential. Additional in vivo
passage(s) of the bacteria in laboratory mice followed by another experimental infection study might reveal differences in the ability of a mouse adapted clone to infect different mouse stocks. Such an experiment could also provide insight into B. elizabethae's
rate of adaptation to a new host. Alternatively, experimental infection studies could be done to evaluate the ability of this bacterium to infect R. norvegicus
and R. rattus
, natural reservoir hosts of B. elizabethae
), to determine if adaptation to other hosts has altered its capacity to infect its natural hosts (29
). Knowledge gained about the zoonotic potential of B. elizabethae
strains can aid us in implementing measures to reduce human infection risk in areas of the world where these strains circulate in small mammal populations.