Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection

Abstract

One of the least understood aspects of the bacterium Streptococcus pneumoniae (pneumococcus) is its transmission from host to host, the critical first step in both the carrier state and the disease state. To date, transmission models have depended on influenza A virus coinfection, which greatly enhances pneumococcal shedding to levels that allow acquisition by a new host. Here, we describe an infant mouse model that can be utilized to study pneumococcal colonization, shedding, and transmission during bacterial monoinfection. Using this model, we demonstrated that the level of bacterial shedding is highest in pups infected intranasally at age 4 days and peaks over the first 4 days postchallenge. Shedding results differed among isolates of five different pneumococcal types. Colonization density was found to be a major factor in the level of pneumococcal shedding and required expression of capsule. Transmission within a litter occurred when there was a high ratio of colonized "index" pups to uncolonized "contact" pups. Transmission was observed for each of the well-colonizing pneumococcal isolates, with the rate of transmission proportional to the level of shedding. This model can be used to examine bacterial and host factors that contribute to pneumococcal transmission without the effects of viral coinfection.T ransmission from one infected individual to another is necessary for most agents of infection. For Streptococcus pneumoniae (the pneumococcus), a leading opportunistic Gram-positive human pathogen, transmission occurs primarily from hosts colonized on the mucosal surfaces of their upper respiratory tract (the carrier state; 1). Bacterial acquisition and colonization of the mucosal surfaces of the nasopharynx by pneumococci are dynamic, transient processes which are generally asymptomatic and occur most commonly during early childhood. Under certain circumstances, however, pneumococci gain access to normally sterile environments within the host, resulting in diseases such as otitis media, pneumonia, sepsis, and meningitis. Acute respiratory infections associated with the pneumococcus represent a significant public health burden, with an estimated 14.5 million cases of serious pneumococcal disease worldwide (2). None of its many disease states, however, is thought to promote pneumococcal contagion (3).While bacterial and host factors contributing to the carrier state have been studied in the natural host and modeled in animals, there is relatively little mechanistic understanding of transmission (4). Person-to-person spread is thought to require close contact, such as within families or day care centers, either directly from nasal secretions or possibly via contact with contaminated surfaces (fomites; 3, 5). Therefore, one of the key steps in pneumococcal contagion involves the exit or shedding of the organism from the respiratory tract of a colonized individual.A factor known to enhance pneumococcal shedding is a concurrent or recent viral respiratory infection (6, 7). Increased rates of carriage associated ...

Host-to-Host Transmission of Streptococcus pneumoniae Is Driven by Its Inflammatory Toxin, Pneumolysin

“…We had previously reported that transmission of strain T4S during mono-infection requires a high ratio (~1:1) of ‘‘index’’ pups colonized at day 4 of age to uncolonized ‘‘contact’’ littermates (Zafar et al, 2016). Under these experimental conditions, T4S transmission from index to contact pups was observed in 28% of pups (Figure 5A).…”

“…Strains deficient in Ply hemolytic activity may escape innate immune surveillance at the expense of a lower transmission rate. Our study depended on a model where high levels of shedding are needed to detect transmission from pup to pup (Zafar et al, 2016). Transmission rates during natural carriage could be higher or lower, and this could reflect the volume or type of secretions the organism induces.…”

“…This gap in knowledge is largely a consequence of a lack of tractable models to study transmission. Our study took advantage of a model that recapitulates many of the key features of pneumococcal transmission, including higher rates among infants, increase by concurrent IAV, and requirement for close contact (Zafar et al, 2016). Our report details the contributions of a specific bacterial factor in respiratory transmission.…”

“…We recently described modifications of the infant mouse model that allows for the study of pneumococcal transmission during mono-infection (Zafar et al, 2016). Since it remains unclear how pneumococci are transmitted in the absence of viral co-infection, in this report, we addressed whether pneumo-coccal-induced inflammation is sufficient to promote its shedding and transmission.…”

Streptococcus pneumoniae: transmission, colonization and invasion

“…This tight population bottleneck during transmission would explain the need for large numbers of shed pneumococci for at least one to be successful in reaching a new host. Accordingly, increasing total shedding per cage by increasing the proportion of colonized index pups per cage to 50% made transmission to ∼30% of contacts possible without the need for IAV co-infection 14 .…”