Conectar
by Kaylee R. Jacobs, Caleb M. Ardizzone, Arkaprabha Banerjee, Evelyn Toh, Xiaoli Zhang, David E. Nelson
Chlamydia are obligate intracellular bacterial pathogens that infect a wide range of vertebrate hosts. Despite having highly conserved genomes, closely related Chlamydia species can exhibit distinct host and tissue tropisms. The host tropisms of the human pathogen Chlamydia trachomatis and the closely related mouse pathogen Chlamydia muridarum are influenced by their ability to evade host immune responses, particularly those mediated by interferon gamma. However, there is evidence that tissue tropism is driven by additional poorly understood host and Chlamydia factors. In this study, we used a forward genetic approach to investigate the mechanisms that mediate C. muridarum tissue tropism. We conducted a tropism screen using a randomly mutagenized C. muridarum library and murine cell lines representing different tissues. We identified a mutant isolate whose growth was restricted in murine rectal and oviduct epithelial cells in an interferon gamma-independent manner. This phenotype was mapped to a missense mutation in tc0237, a gene that mediates the affinity of C. muridarum for cultured human epithelial cells. Our analysis of growth dynamics showed that the tc0237 mutant exhibits a developmental delay in rectal epithelial cells. Together, these results suggest that TC0237 plays a role in C. muridarum tissue tropism.The cardiovascular (circulatory) system is a closed-loop system. The dynamic interaction of the heart and vascular system plays a pivotal role in maintaining adequate cardiac output. Heart failure (HF) is commonly described as a problem of the pump, that is, mechanical myocardial failure causing poor perfusion to the body. Still, the contribution of the vasculature is often neglected. Acute decompensated heart failure (ADHF) carries a poor prognosis and is often accompanied by concomitant chronic kidney disease (CKD) and acute kidney injury (AKI), which inevitably lead to adverse outcomes. The interaction of the heart with the vasculature is conceptualised as ventricular–vascular (arterial) coupling. Arterial stiffness, a non-traditional risk factor for cardiovascular disease, can be measured non-invasively using carotid–femoral pulse wave velocity (cf-PWV). High cf-PWV values mimicking increased arterial stiffness could be a causational factor towards precipitating ADHF or AKI. This study aims to assess whether cf-PWV is higher during the hospitalisation phase of patients with HF (ADHF) and CKD (AKI in CKD) compared with stable compensated HF and stable CKD.
This prospective non-randomised observational study aims to recruit 120 patients aged≥60 years. Arterial stiffness will be assessed in three groups. These groups are decompensated HF with reduced ejection fraction (n=40), decompensated HF with preserved ejection fraction (n=40) and AKI in CKD stage 3a, 3b and 4, n=40. After 4 weeks from hospital discharge, patients in a stable, compensated state will be asked to attend a follow-up clinic visit to repeat the cf-PWV measurement. The primary outcome measure is variation in cf-PWV during hospitalisation against follow-up.
Ethical approval was granted in October 2021 (REC reference 21/EM/0239), recruitment started in February 2022 and the results are expected in late 2025. The findings will be published in peer-reviewed journals.
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