EmrE is the archetypical member of the small multidrug resistance transporter family and confers resistance to a wide range of disinfectants and dyes known as quaternary cation compounds (QCCs). The aim of this study was to examine which conserved amino acids play an important role in substrate selectivity. On the basis of a previous analysis of EmrE homologues, a total of 33 conserved residues were targeted for cysteine or alanine replacement within EmrE. The antimicrobial resistance of each EmrE variant expressed in strain JW0451 (lacking dominant pump ) to a collection of 16 different QCCs was tested using agar spot dilution plating to determine MIC values. The results determined that only a few conserved residues were drug polyselective, based on ≥4-fold decreases in MIC values: the active-site residue E14 (E14D and E14A) and 4 additional conserved residues (A10C, F44C, L47C, W63A). EmrE variants I11C, V15C, P32C, I62C, L93C, and S105C enhanced resistance to polyaromatic QCCs, while the remaining EmrE variants reduced resistance to one or more QCCs with shared chemical features: acylation, tri- and tetraphenylation, aromaticity, and dicationic charge. Mapping of EmrE variants onto transmembrane helical wheel projections using the highest resolved EmrE structure suggests that polyselective EmrE variants were located closest to the helical faces surrounding the predicted drug binding pocket, while EmrE variants with greater drug specificity mapped onto distal helical faces. This study reveals that few conserved residues are essential fordrug polyselectivity and indicates that aromatic QCC selection involves a greater portion of conserved residues than that in other QCCs.

Burkholderia cepacia complex (Bcc), which includes B. cenocepacia and B. multivorans, pose a life-threatening risk to patients with cystic fibrosis. Eradication of Bcc is difficult due to the high level of intrinsic resistance to antibiotics, and failure of many innate immune cells to control the infection. Because of the pathogenesis of Bcc infections, we wondered if a novel mechanism of microbial host defense involving direct antibacterial activity by natural killer (NK) cells might play a role in the control of Bcc. We demonstrate that NK cells bound Burkholderia, resulting in Src family kinase activation as measured by protein tyrosine phosphorylation, granule release of effector proteins such as perforin and contact-dependent killing of the bacteria. These studies provide a means by which NK cells could play a role in host defense against Bcc infection.

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BackgroundMany studies have been conducted worldwide and in the Kingdom of Saudi Arabia (KSA) during the current coronavirus disease 2019 (COVID-19) pandemic to assess the factors affecting COVID-19 vaccine acceptance. However, only some of these studies have adopted the Health Belief Model (HBM). This study aimed to assess the demographic characteristics and socio-psychological variables affecting the willingness to receive the COVID-19 vaccine among the general adult population in the KSA using the basic elements of the HBM. MethodsA cross-sectional survey-based study was conducted. A Google Form questionnaire comprising 30 questions was distributed electronically using social media platforms. A univariate analysis using chi-square testing identified candidate variables for the multivariate logistic regression at a p-value of <.05 at 95% confidence interval (CI) set as a cut-off point. Multivariate logistic regression analysis was used to determine the association between multiple predictor variables and the dichotomized COVID-19 vaccine acceptance variable. ResultsA total of 1939 individuals participated in the current study. More than 73% were willing to take the vaccine, while the rest were either not willing (14.6%) or not sure (12.1%). The results showed that men were 1.29 times more likely to receive the COVID-19 vaccine than women (odds ratio, or OR = 1.29, 95% CI = 1.01-1.64, p = .04); those who were or had been a healthcare worker (HCW) were 1.43 times more likely to receive the COVID-19 vaccine compared with those who had never been a HCW (OR = 1.43, 95% CI = 1.10-1.87, p = .01). We found that perceiving the risk of contracting COVID-19 (OR = 2.86, 95% CI = 1.47-5.55, p = .00) and perceiving the severity of the disease (OR = 2.07, 95% CI = 1.08-3.96, p = .03) were positively associated with the willingness to receive the vaccine. Perceived barriers such as ineffectiveness of the vaccine (OR = 0.28, 95% CI = 0.18-0.44, p < .001), or believing the vaccine is just a media advertisement (OR = 0.56, 95% CI = 0.35-0.87, p = .01) were negative predictors of acceptance of the vaccine. Moreover, perceiving the benefits, such as life going back to normal (OR = 2.28, 95% CI = 1.37-3.77, p = .00) and recognizing the importance of the annual flu vaccine (OR = 3.43, 95% CI = 2.29-5.14, p < .001), were found to be positive predictors of acceptance of the vaccine. Finally, we also found that cues to action were positively associated with vaccine acceptance, that is, participants who were encouraged by their doctors (OR = 1.75, 95% CI = 1.17-2.60, p = .01), and family members or friends (OR = 2.89, 95% CI = 1.94-4.32, p < .001) were more willing to receive the COVID-19 vaccine than those who were not. ConclusionsThe current study provides valuable insights into the determinants of vaccine acceptance and hesitancy based on the HBM from a cognitive perspective. This could be useful in helping the government establish public health programs aimed at addressing barriers and false beliefs among the adult population, which ...

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