The development of novel antibiotics is essential because the current arsenal of antimicrobials will soon be ineffective due to the widespread occurrence of antibiotic resistance. The development of naturally occurring cationic antimicrobial peptides (CAMPs) for therapeutics to combat antibiotic resistance has been hampered by high production costs and protease sensitivity, among other factors.

Ceragenins are a family of synthetic amphipathic molecules designed to mimic the properties of naturally-occurring cationic antimicrobial peptides (CAMPs). Although ceragenins have potent antimicrobial activity, whether their mode of action is similar to that of CAMPs has remained elusive. Here we report the results of a comparative study of the bacterial responses to two well-studied CAMPs, LL37 and colistin, and two ceragenins with related structures, CSA13 and CSA131. Using transcriptomic and proteomic analyses, we found that Escherichia coli responds similarly to both CAMPs and ceragenins by inducing a Cpx envelope stress response. However, whereas E. coli exposed to CAMPs increased expression of genes involved in colanic acid biosynthesis, bacteria exposed to ceragenins specifically modulated functions related to phosphate transport, indicating distinct mechanisms of action between these two classes of molecules. Although traditional genetic approaches failed to identify genes that confer high-level resistance to ceragenins, using a Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) approach we identified E. coli essential genes that when knocked down modify sensitivity to these molecules. Comparison of the essential gene-antibiotic interactions for each of the CAMPs and ceragenins identified both overlapping and distinct dependencies for their antimicrobial activities. Overall, this study indicates that while some bacterial responses to ceragenins overlap with those induced by naturally-occurring CAMPs, these synthetic molecules target the bacterial envelope using a distinctive mode of action.

Purpose: To study a primarily Hispanic population of adults younger than 65 to determine if COVID-19 patients with a concurrent delirium diagnosis had worse clinical outcomes in terms of hospital stay, ventilation and mortality, than those without a delirium diagnosis. Methods: After approval by the appropriate Institutional Review Board, a retrospective cohort study was performed looking at demographics, vital statistics, and clinical outcomes of patients aged 18-65 admitted to a hospital in the United States - Mexico border region with COVID-19 between March 1 and June 30, 2020. Data were analyzed using Fisher's exact test, or an unpaired t-test where appropriate, and a univariate analysis was performed to establish relative risk. Confidence intervals were set at 95% and p values ≤0.05 were considered significant. Results: 133 patients with confirmed COVID-19 diagnoses (58% men, 92% Hispanic) were included. Mean age was 50.5 with a standard deviation of 11.7 years (range 20-65 years). The prevalence of delirium was 6%. Fifty percent of delirium patients died during hospitalization compared to 15% of patients without delirium. Patients with delirium were found to spend more days hospitalized, in the intensive care unit, and intubated than their counterparts without delirium. Delirium was associated with increased risk of being placed on mechanical ventilation (RR 3.91, 95% CI 1.46-10.41, p value 0.006). Conclusions: Delirium was associated with worse COVID-19 outcomes independent of age. COVID-19 patients need to be actively assessed for signs of delirium and appropriate precautionary measures should be implemented. Proper documentation of delirium is key to continue learning about the incidence of delirium in COVID-19 patients.