Serratia marcescens is an opportunistic nosocomial pathogen and causes wound and burn infections. It shows high resistance to antibiotics and its pathogenicity is mediated by an arsenal of virulence factors. Another therapeutic option to such infections is targeting quorum sensing (QS), which controls the expression of different S. marcescens virulence factors. Prevention of QS can deprive S. marcescens from its bacterial virulence without applying stress on the bacterial growth and facilitates the eradication of the bacteria by immunity. The objective of the current study is to explore the antimicrobial and antivirulence activities of xylitol against S. marcescens. Xylitol could inhibit the growth of S. marcescens. Sub-inhibitory concentrations of xylitol could inhibit biofilm formation, reduce prodigiosin production, and completely block protease activity. Moreover, xylitol decreased swimming motility, swarming motility and increased the sensitivity to hydrogen peroxide. The expression of rsmA, pigP, flhC, flhD fimA, fimC, shlA bsmB, and rssB genes that regulate virulence factor production was significantly downregulated by xylitol. In silico study showed that xylitol could bind with the SmaR receptor by hydrophobic interaction and hydrogen bonding, and interfere with the binding of the natural ligand with SmaR receptor. An in vivo mice survival test confirmed the ability of xylitol to protect mice against the virulence of S. marcescens. In conclusion, xylitol is a growth and virulence inhibitor in S. marcescens and can be employed for the treatment of S. marcescens wound and burn infections.
The present study involved in vivo evaluation of the growth promoting effects of thymol and thymol nanoemulsion and their protection against Salmonella Typhimurium infection in broilers. One-day old 2400 chicks were randomly divided into eight groups; negative and positive control groups fed basal diet without additives and thymol and thymol nanoemulsion groups (0.25, 0.5 and 1% each). At d 23, all chicks except negative control were challenged with S. Typhimurium. Over the total growing period, birds fed 1% thymol nanoemulsion showed better growth performance even after S. Typhimurium challenge, which came parallel with upregulation of digestive enzyme genes (AMY2A, PNLIP and CCK). Additionally, higher levels of thymol nanoemulsion upregulated the expression of MUC-2, FABP2, IL-10, IgA and tight junction proteins genes and downregulated IL-2 and IL-6 genes expression. Moreover, 1% thymol nanoemulsion, and to lesser extent 0.5% thymol nanoemulsion and 1% thymol, corrected the histological alterations of cecum and liver postinfection. Finally, supplementation of 1% thymol, 0.5 and 1% thymol nanoemulsion led to increased Lactobacilli counts and decreased S. Typhimurium populations and downregulated invA gene expression postinfection. This first report of supplying thymol nanoemulsion in broiler diets proved that 1% nano-thymol is a potential growth promoting and antibacterial agent.
Multidrug resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) is a superbug pathogen that causes serious diseases. One of the main reasons for the lack of the effectiveness of antibiotic therapy against infections caused by this resistant pathogen is the recalcitrant nature of MRSA biofilms, which results in an increasingly serious situation worldwide. Consequently, the development of innovative biofilm inhibitors is urgently needed to control the biofilm formation by this pathogen. In this work, we thus sought to evaluate the biofilm inhibiting ability of some promising antibiofilm agents such as zinc oxide nanoparticles (Zno NPs), proteinase K, and hamamelitannin (HAM) in managing the MRSA biofilms. Different phenotypic and genotypic methods were used to identify the biofilm producing MDR MRSA isolates and the antibiofilm/antimicrobial activities of the used promising agents. Our study demonstrated strong antibiofilm activities of ZnO NPs, proteinase K, and HAM against MRSA biofilms along with their transcriptional modulation of biofilm (intercellular adhesion A, icaA) and quorum sensing (QS) (agr) genes. Interestingly, only ZnO NPs showed a powerful antimicrobial activity against this pathogen. Collectively, we observed overall positive correlations between the biofilm production and the antimicrobial resistance/agr genotypes II and IV. Meanwhile, there was no significant correlation between the toxin genes and the biofilm production. The ZnO NPs were recommended to be used alone as potent antimicrobial and antibiofilm agents against MDR MRSA and their biofilm-associated diseases. On the other hand, proteinase-K and HAM can be co-administrated with other antimicrobial agents to manage such types of infections.
The economic and humanistic impact of COVID-19 pandemic is enormous globally. No definitive treatment exists, hence accelerated development and approval of COVID-19 vaccines, offers a unique opportunity for COVID-19 prevention and control. Vaccine hesitancy may limit the success of vaccine distribution in Africa, therefore we assessed the potentials for coronavirus vaccine hesitancy and its determinants among Africans. An online cross-sectional African-wide survey was administered in Arabic, English, and French languages. Questions on demographics, self-reported health status, vaccine literacy, knowledge and perception on vaccines, past experience, behavior, infection risk, willingness to receive and affordability of the SARS-COV-2 vaccine were asked. Data were subjected to descriptive and inferential statistics. A total of 5,416 individuals completed the survey. Approximately, 94% were residents of 34 African countries while the other Africans live in the Diaspora. Only 63% of all participants surveyed were willing to receive the COVID-19 vaccination as soon as possible and 79% were worried about its side effects. Thirty-nine percent expressed concerns of vaccine-associated infection. The odds of vaccine hesitancy was 0.28 (95% CI: 0.22, 0.30) among those who believed their risk of infection was very high, compared to those who believed otherwise. The odds of vaccine hesitancy was one-fifth (OR = 0.21, 95% CI: 0.16, 0.28) among those who believed their risk of falling sick was very high, compared to those who believed their risk of falling very sick was very low. The OR of vaccine hesitancy was 2.72 (95% CI: 2.24, 3.31) among those who have previously refused a vaccine for themselves or their child compared to counterparts with no self-reported history of vaccine hesitancy. Participants want the vaccines to be mandatory (40%), provided free of charge (78%) and distributed in homes and offices (44%). COVID-19 vaccine hesitancy is substantial among Africans based on perceived risk of coronavirus infection and past experiences.
Foodborne pathogens have been associated with severe and complicated diseases. Therefore, these types of infections are a concern for public health officials and food and dairy industries. Regarding the wide-spread multidrug resistant (MDR) and extensively drug resistant (XDR) foodborne pathogens such as Salmonella Enteritidis (S. Enteritidis), new and alternative therapeutic approaches are urgently needed. Therefore, we investigated the antimicrobial, anti-virulence, and immunostimulant activities of a stable formulation of thymol as thymol nanoemulsion in an in vivo approach. Notably, treatment with 2.25% thymol nanoemulsion led to a pronounced improvement in the body weight gain and feed conversion ratio in addition to decreases in the severity of clinical findings and mortality percentages of challenged chickens with XDR S. Enteritidis confirming its pronounced antimicrobial activities. Moreover, thymol nanoemulsion, at this dose, had protective effects through up-regulation of the protective cytokines and down-regulation of XDR S. Enteritidis sopB virulence gene and interleukins (IL)-4 and IL-10 cytokines as those hinder the host defenses. Furthermore, it enhanced the growth of gut Bifidobacteria species, which increases the strength of the immune system. For that, we suggested the therapeutic use of thymol nanoemulsion against resistant foodborne pathogens. Finally, we recommended the use of 2.25% thymol nanoemulsion as a feed additive for immunocompromised individuals as well as in the veterinary fields.
Candida albicans is the causative agent of fatal systemic candidiasis. Due to limitations of antifungals, new drugs are needed. The anti-virulence effect of plant essential oils (EOs) was evaluated against clinical C. albicans isolates including cinnamon, clove, jasmine and rosemary oils. Biofilm, phospholipase and hemolysin were assessed phenotypically. EOs were evaluated for their anti-virulence activity using phenotypic methods as well as scanning electron microscopy (SEM) and atomic force microscopy (AFM). Among the C. albicans isolates, biofilm, phospholipase and hemolysins were detected in 40.4, 86.5 and 78.8% of isolates, respectively. Jasmine oil showed the highest anti-biofilm activity followed by cinnamon, clove and rosemary oils. SEM and AFM analysis showed reduced adherence and roughness in the presence of EOs. For phospholipase, rosemary oil was the most inhibitory, followed by jasmine, cinnamon and clove oils, and for hemolysins, cinnamon had the highest inhibition followed by jasmine, rosemary and clove oils. A molecular docking study revealed major EO constituents as promising inhibitors of the Als3 adhesive protein, with the highest binding for eugenol, followed by 1,8-cineole, 2-phenylthiolane and cinnamaldehyde. In conclusion, EOs have a promising inhibitory impact on Candida biofilm, phospholipase and hemolysin production, hence EOs could be used as potential antifungals that impact virulence factors.
Campylobacter jejuni (C. jejuni) are able to colonise and infect domestic poultry and also pose a risk for humans. The aim of this study was to determine the extent of genotypic diversity among C. jejuni isolates recovered from avian and human sources in Egypt. Furthermore, the short variable region (SVR) of flagellin A (flaA) gene was analysed for the presence of allelic variants. Our results showed that C. jejuni isolates differ in their capacity to harbour each of the virulence genes alone or when present in various combinations. The flaA gene was detected in all C. jejuni strains and none of the strains had all the studied virulence genes together. When considering C. jejuni strains from the investigated sources, the cdtC gene was the most similar, while the cdtB and iam genes were the most dissimilar. We could identify 13 novel alleles in the analysed strains. The analyses of virulence gene patterns, flaA gene sequences and allelic variants showed that C. jejuni strains from different sources overlapped largely suggesting potential involvement of poultry in transmitting C. jejuni to humans. We also found that the strains isolated from the same host were highly heterogeneous, with chicken strains exhibiting the highest diversity. Moreover, the human strains were clustered closer to chicken ones than to those from pigeon. The results of this study should be taken into consideration when assessing the epidemiology and risk potential of Egyptian C. jejuni not only in poultry, but also in humans.
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