Temporal Dynamics of Early-Phase Transmission ofYersinia pestisby Unblocked Fleas: Secondary Infectious Feeds Prolong Efficient Transmission byOropsylla montana(Siphonaptera: Ceratophyllidae)

Plague, caused by Yersinia pestis, is characterized by quiescent periods punctuated by rapidly spreading epizootics. The classical ‘blocked flea’ paradigm, by which a blockage forms in the flea’s proventriculus on average 1–2 weeks post-infection (p.i.), forces starving fleas to take multiple blood meals, thus increasing opportunities for transmission. Recently, the importance of early-phase transmission (EPT), which occurs prior to blockage formation, has been emphasized during epizootics. Whilst the physiological and molecular mechanisms of blocked flea transmission are well characterized, the pathogen–vector interactions have not been elucidated for EPT. Within the blocked flea model, Yersinia murine toxin (Ymt) has been shown to be important for facilitating colonization of the midgut within the flea. One proposed mechanism of EPT is the regurgitation of infectious material from the flea midgut during feeding. Such a mechanism would require bacteria to colonize and survive for at least brief periods in the midgut, a process that is mediated by Ymt. Two key bridging vectors of Y. pestis to humans, Oropsylla montana (Siphonaptera: Ceratophyllidae) or Xenopsylla cheopis (Siphonaptera: Pulicidae), were used in our study to test this hypothesis. Fleas were infected with a mutant strain of Y. pestis containing a non-functional ymt that was shown previously to be incapable of colonizing the midgut and were then allowed to feed on SKH-1 mice 3 days p.i. Our results show that Ymt was not required for EPT by either flea species.

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Demonstration of Early-Phase Transmission of Yersinia pestis by the Mouse Flea, Aetheca wagneri (Siphonaptera: Ceratophylidae), and Implications for the Role of Deer Mice as Enzootic Reservoirs

Journal of Medical Entomology ◽

10.1603/0022-2585(2008)45[1160:doetoy]2.0.co;2 ◽

2008 ◽

Vol 45 (6) ◽

pp. 1160-1164 ◽

Cited By ~ 10

Author(s):

Rebecca J. Eisen ◽

Jennifer L. Holmes ◽

Anna M. Schotthoefer ◽

Sara M. Vetter ◽

John A. Montenieri ◽

...

Keyword(s):

Yersinia Pestis ◽

Early Phase ◽

Deer Mice ◽

Phase Transmission

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Comparison of the transmission efficiency and plague progression dynamics associated with two mechanisms by which fleas transmit Yersinia pestis

PLoS Pathogens ◽

10.1371/journal.ppat.1009092 ◽

2020 ◽

Vol 16 (12) ◽

pp. e1009092

Author(s):

Christopher F. Bosio ◽

Clayton O. Jarrett ◽

Dana P. Scott ◽

Jonathan Fintzi ◽

B. Joseph Hinnebusch

Keyword(s):

Yersinia Pestis ◽

Blood Meal ◽

Early Phase ◽

Blood Feeding ◽

Rapid Onset ◽

Transmission Efficiency ◽

Intradermal Injection ◽

Terminal Disease ◽

Systemic Spread ◽

Phase Transmission

Yersinia pestis can be transmitted by fleas during the first week after an infectious blood meal, termed early-phase or mass transmission, and again after Y. pestis forms a cohesive biofilm in the flea foregut that blocks normal blood feeding. We compared the transmission efficiency and the progression of infection after transmission by Oropsylla montana fleas at both stages. Fleas were allowed to feed on mice three days after an infectious blood meal to evaluate early-phase transmission, or after they had developed complete proventricular blockage. Transmission was variable and rather inefficient by both modes, and the odds of early-phase transmission was positively associated with the number of infected fleas that fed. Disease progression in individual mice bitten by fleas infected with a bioluminescent strain of Y. pestis was tracked. An early prominent focus of infection at the intradermal flea bite site and dissemination to the draining lymph node(s) soon thereafter were common features, but unlike what has been observed in intradermal injection models, this did not invariably lead to further systemic spread and terminal disease. Several of these mice resolved the infection without progression to terminal sepsis and developed an immune response to Y. pestis, particularly those that received an intermediate number of early-phase flea bites. Furthermore, two distinct types of terminal disease were noted: the stereotypical rapid onset terminal disease within four days, or a prolonged onset preceded by an extended, fluctuating infection of the lymph nodes before eventual systemic dissemination. For both modes of transmission, bubonic plague rather than primary septicemic plague was the predominant disease outcome. The results will help to inform mathematical models of flea-borne plague dynamics used to predict the relative contribution of the two transmission modes to epizootic outbreaks that erupt periodically from the normal enzootic background state.

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Predicted sensory consequences of voluntary actions modulate amplitude and temporal dynamics of preceding readiness potentials

10.1101/101402 ◽

2017 ◽

Author(s):

Daniel Reznik ◽

Shiri Simon ◽

Roy Mukamel

Keyword(s):

Motor Activity ◽

Early Phase ◽

Healthy Subjects ◽

Temporal Dynamics ◽

Readiness Potential ◽

Button Press ◽

Eeg Signal ◽

Eeg Data ◽

Readiness Potentials ◽

Neural Signature

AbstractSelf-generated, voluntary actions, are preceded by a slow negativity in the scalp electroencephalography (EEG) signal recorded from frontal regions (termed ‘readiness potential’; RP). This signal, and its lateralized subcomponent (LRP), is mainly regarded as preparatory motor activity associated with the forthcoming motor act. However, it is not clear whether this neural signature is associated with preparatory motor activity, expectation of its associated sensory consequences, or both. Here we recorded EEG data from 12 healthy subjects while they performed self-paced button presses with their right index and middle fingers. In one condition (motor+sound) these button-presses triggered a sound while in another (motor-only) they did not. Additionally, subjects passively listened to sounds delivered in expected timings (sound-only). We found that the RP amplitude (locked to time of button press) was significantly more negative in the motor+sound compared with motor-only conditions starting ~1.4 seconds prior to button press. Importantly, no signal negativity was observed prior to expected sound delivery in the sound-only condition. Thus, the differences in RP amplitude between motor+sound and motor-only conditions are beyond differences in mere expectation of a forthcoming auditory sound. No significant differences between the two conditions were obtained in the LRP component. Our results suggest that expected auditory consequences are encoded in the early phase of the RP preceding the voluntary actions that generate them.

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Biofilm formation is not required for early-phase transmission of Yersinia pestis

Microbiology ◽

10.1099/mic.0.037952-0 ◽

2010 ◽

Vol 156 (7) ◽

pp. 2216-2225 ◽

Cited By ~ 38

Author(s):

Sara M. Vetter ◽

Rebecca J. Eisen ◽

Anna M. Schotthoefer ◽

John A. Montenieri ◽

Jennifer L. Holmes ◽

...

Keyword(s):

Yersinia Pestis ◽

Early Phase ◽

Biofilm Formation ◽

Parent Strain ◽

Rapid Spread ◽

Dependent Model ◽

Phase Transmission ◽

Oropsylla Montana ◽

Mammal Host

Early-phase transmission (EPT) is a recently described model of plague transmission that explains the rapid spread of disease from flea to mammal host during an epizootic. Unlike the traditional blockage-dependent model of plague transmission, EPT can occur when a flea takes its first blood meal after initially becoming infected by feeding on a bacteraemic host. Blockage of the flea gut results from biofilm formation in the proventriculus, mediated by the gene products found in the haemin storage (hms) locus of the Yersinia pestis chromosome. Although biofilms are required for blockage-dependent transmission, the role of biofilms in EPT has yet to be determined. An artificial feeding system was used to feed Xenopsylla cheopis and Oropsylla montana rat blood spiked with the parental Y. pestis strain KIM5(pCD1)+, two different biofilm-deficient mutants (ΔhmsT, ΔhmsR), or a biofilm-overproducer mutant (ΔhmsP). Infected fleas were then allowed to feed on naïve Swiss Webster mice for 1–4 days after infection, and the mice were monitored for signs of infection. We also determined the bacterial loads of each flea that fed upon naïve mice. Biofilm-defective mutants transmitted from X. cheopis and O. montana as efficiently as the parent strain, whereas the EPT efficiency of fleas fed the biofilm-overproducing strain was significantly less than that of fleas fed either the parent or a biofilm-deficient strain. Fleas infected with a biofilm-deficient strain harboured lower bacterial loads 4 days post-infection than fleas infected with the parent strain. Thus, defects in biofilm formation did not prevent flea-borne transmission of Y. pestis in our EPT model, although biofilm overproduction inhibited efficient EPT. Our results also indicate, however, that biofilms may play a role in infection persistence in the flea.

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