Biology subjects

Norton, E. B.

Publications and source records attributed to Norton, E. B..

3 recordsLinked to original sources

bioRxiv2024

Comparative Aerosol Persistence of Hypermucoid Klebsiella pneumoniae

Klebsiella pneumoniae is becoming an increasing cause for concern due to antibiotic resistance and emerging hypervirulent strains. It results in a wide variety of infections, most commonly pneumonia. Immunocompromised individuals and those needing ventilators are among the most at-risk for infection and systemic spread. It is crucial to further understand the behavior of K. pneumoniae to prevent future infections and severe illness. In the past, little research has examined K. pneumoniae in the air to determine whether aerosol transmission is a realistic infection pathway. Therefore, we observed survival of K. pneumoniae suspensions using a 10.7 L custom-built rotating chamber, characterizing laboratory and clinical strains in separate aerosol events. Airborne bacterial suspensions were assessed by culture and quantitative polymerase chain reaction (qPCR). The K2 laboratory strain remained viable until yielding no colony forming units (CFU) at 16 hours. K1 clinical strain did not become unculturable until 32 hours. For each strain, qPCR data showed Ct values slightly increased as time in drum also increased. Our data suggests K. pneumoniae can survive after multiple hours in the air, indicating aerosol transmission of K. pneumoniae is a possible infection pathway.

microbiology↗

bioRxiv2022

Intermittent Cytomegalovirus Infection Alters Neurobiological Metabolism and Induces Cognitive Deficits in Mice

Risk factors contributing to dementia are multifactorial. Pathogens as risk factors for dementia is largely correlative with few causal relationships. Here, we demonstrate that intermittent cytomegalovirus (CMV) infection in mice, mimicking human chronic infection and reactivation/reinfection events, alters blood brain barrier (BBB) metabolic pathways. An increase in basal mitochondrial function is observed in brain microvasculature endothelial cells (BMEC) at 12 months post infection but not at earlier time points and is accompanied by elevated levels of superoxide, indicative of oxidative stress. Further, these mice score lower in cognitive assays as compared to age-matched controls. Our data show that repeated systemic infection with CMV, alters BBB metabolic function and impacts cognition. These observations provide mechanistic insights through which pathogens contribute to the progression of pathologies associated with dementia. In BriefMechanistic evidence supporting an infectious etiology of dementia (e.g. Alzheimers Disease) are poorly defined. Harrison et al., show that intermittent infection with cytomegalovirus metabolically rewires the blood brain barrier and neighboring glial cells altering their function, resulting in decreased cognitive function.

neuroscience↗

bioRxiv2020

Enteropathy-induced regulatory T cells inhibit intestinal CD4+ T cell responses against oral vaccines

Environmental Enteric Dysfunction (EED) is an intestinal disease caused by malnutrition and infection that leads to malabsorption and stunting. EED is also associated with a reduced efficacy of oral vaccines. We show in a microbiota and diet-dependent model of EED that oral vaccine-specific CD4+ T cell responses fail in the small intestine but responses in the draining lymph node were unaffected. Accordingly, the number of immunosuppressive ROR{gamma}T+FOXP3+ Tregs in the small intestine inversely correlated with the response to oral vaccination. Depletion of ROR{gamma}T+FOXP3+ Tregs indicated that they were necessary for EED-associated inhibition of the vaccine response. Additionally, ROR{gamma}T+FOXP3+ Tregs are important to regulate EED-associated inflammation as their depletion significantly worsened stunting. We have shown that EED-associated intestinal inflammation leads to a localized intestinal blockade of CD4 T cell immunity. These results support a modular model for immunity where tissue responses can be regulated independently of systemic immunity to prevent autoinflammation.

immunology↗