An important yet poorly understood facet in the life cycle of a successful pathogen is the host-to-host transmission. Hospital-acquired infections (HAI) resulting from the transmission of drug-resistant pathogens affect hundreds of millions of patients worldwide. Klebsiella pneumoniae (Kpn), a gram-negative bacterium, is notorious for causing HAI, with many of these infections difficult to treat as Kpn has become multi-drug resistant. Epidemiological studies suggest that Kpn host-to-host transmission requires close contact and generally occurs through the fecal-oral route. Herein, we describe a murine model that can be utilized to study mucosal (oropharynx and gastrointestinal [GI]) colonization, shedding within feces, and transmission of Kpn through the fecal-oral route. Using an oral route of inoculation, and fecal shedding as a marker for GI colonization, we show that Kpn can asymptomatically colonize the GI tract of immunocompetent mice, and modifies the host GI microbiota. Colonization density within the GI tract and levels of shedding in the feces differed among the clinical isolates tested. A hypervirulent Kpn isolate was able to translocate from the GI tract and cause hepatic infection that mimicked the route of human infection. Expression of the capsule was required for colonization and, in turn, robust shedding. Furthermore, Kpn carrier mice were able to transmit to uninfected cohabitating mice. Lastly, treatment with antibiotics led to changes in the host microbiota and development of a transient super-shedder phenotype, which enhanced transmission efficiency. Thus, this model can be used to determine the contribution of host and bacterial factors towards Kpn dissemination.
The biological cost associated with colistin resistance in
Klebsiella pneumoniae
was examined using a murine model of
K. pneumoniae
gut colonization and fecal-oral transmission. A common mutation resulting in colistin resistance in
K. pneumoniae
is a loss-of-function mutation of the small regulatory protein MgrB that regulates the two-component system PhoPQ.
The ability to sense and respond rapidly to the dynamic environment of the upper respiratory tract (URT) makes
Streptococcus pneumoniae
(
Spn
) a highly successful human pathogen. Two-component systems (TCSs) of
Spn
sense and respond to multiple signals it encounters allowing
Spn
to adapt and thrive in various host sites.
Spn
TCS have been implicated in their ability to promote pneumococcal colonization of the URT and virulence.
The ability to sense and respond rapidly to the dynamic environment of the upper respiratory tract (URT) makes Streptococcus pneumoniae (Spn) a highly successful human pathogen. Two-component systems (TCS) of Spn sense and respond to multiple signals it encounters allowing Spn to adapt and thrive in various host sites. Spn TCS have been implicated in their ability to promote pneumococcal colonization of the URT and virulence. As the disease state can be a dead-end for a pathogen, we considered whether TCS would contribute to pneumococcal transmission. Herein, we determined the role of YesMN, an understudied TCS of Spn, and observe that YesMN contributes towards pneumococcal shedding and transmission but is not essential for colonization. The YesMN regulon includes genes involved in zinc homeostasis and glycan metabolism, which are upregulated during reduced zinc availability in a YesMN dependent fashion. Thus, we identify the YesMN regulon and the molecular signals it senses that lead to the activation of genes involved in zinc homeostasis and glycan metabolism. Furthermore, in contract to Spn mono-infection, we demonstrate that YesMN is critical for high pneumococcal density in the URT during influenza A (IAV) coinfection. We attribute reduced colonization of the yesMN mutant due to increased association with and clearance by the mucus covering the URT epithelial surface. Thus, our results highlight the dynamic interactions that occur between Spn and IAV in the URT, and the role that TCS play in modulation of these interactions.
This intervention extends learning strategies research into authentic learning environments. It shows college biology students can learn to generate analogies as a learning strategy and get better at doing so. Finally, students’ generated-analogy quality predicts analogical reasoning and knowledge of cognition.
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