Attention:The NSF Public Access Repository (PAR) system and access will be unavailable from 5:00 PM ET until 8:00 PM ET on Friday, September 11 due to maintenance. We apologize for the inconvenience.


Title: Cannabis sativa CBD Extract Exhibits Synergy with Broad-Spectrum Antibiotics against Salmonella enterica subsp. Enterica serovar typhimurium
New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species, it is important to examine potential interactions between CBD and common therapeutics such as broad-spectrum antibiotics. In this study it is demonstrated that CBD-antibiotic (combination of CBD and antibiotic) co-therapy can effectively fight Salmonella typhimurium (S. typhimurium) via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics (ampicillin, kanamycin, and polymyxin B) for potential CBD-antibiotic co-therapy. In this study, it is revealed that S. typhimurium growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating S. typhimurium.  more » « less
Award ID(s):
1646729
PAR ID:
10417415
Author(s) / Creator(s):
; ; ; ; ; ;
Date Published:
Journal Name:
Microorganisms
Volume:
10
Issue:
12
ISSN:
2076-2607
Page Range / eLocation ID:
2360
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Products derived from Cannabis sativa L. have gained increased interest and popularity. As these products become common amongst the public, the health and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in the literature, the antibacterial properties of cannabidiol (CBD) have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and S. typhimurium. In this study, we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against S. typhimurium and S. newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment. 
    more » « less
  2. Bacterial infection has traditionally been treated with antibiotics, but their overuse is leading to the development of antibiotic resistance. This may be mitigated by alternative approaches to prevent or treat bacterial infections without utilization of antibiotics. Among the alternatives is the use of photo-responsive antimicrobial nanoparticles and/or nanocomposites, which present unique properties activated by light. In this study, we explored the combined use of titanium oxide and polydopamine to create nanoparticles with photocatalytic and photothermal antibacterial properties triggered by visible or near-infrared light. Furthermore, as a proof-of-concept, these photo-responsive nanoparticles were combined with mussel-inspired catechol-modified hyaluronic acid hydrogels to form novel light-driven antibacterial nanocomposites. The materials were challenged with models of Gram-negative and Gram-positive bacteria. For visible light, the average percentage killed (PK) was 94.6 for E. coli and 92.3 for S. aureus. For near-infrared light, PK for E. coli reported 52.8 and 99.2 for S. aureus. These results confirm the exciting potential of these nanocomposites to prevent the development of antibiotic resistance and also to open the door for further studies to optimize their composition in order to increase their bactericidal efficacy for biomedical applications. 
    more » « less
  3. Abstract Combating antibiotic-resistant bacteria has been a long-lasting challenge. This study investigated the photoactivated antibacterial function of carbon dots (CDots) in combination with antibiotics and membrane destabilizing agents as co-agents against drug resistant bacteriaE. faecalisandL. monocytogenes. The results of the study demonstrated that CDots in combination with the membrane destabilizing agent poly-L-lysine as co-agent exhibited significant enhancement in the overall antibacterial activity, especially with the longer poly-L-lysine, achieving complete inactivation of cells in the samples with ~ 8 log viable cell reduction. The combination of CDots with bacterial resistant antibiotics streptomycin, erythromycin, or tetracycline, did not expectedly enhance the overall antibacterial activity of photoactive CDots toE. faecalis, in contrast, the combination with streptomycin significantly reduced the antibacterial activity of CDots. Implications of these experimental results toward the understanding of mechanistical action of photoexcited CDots were discussed. The study demonstrated that appropriately selected co-agents could effectively enhance the photoactivated antibacterial function of CDots and its potential to combat drug resistant pathogens. 
    more » « less
  4. Garrido, Daniel (Ed.)
    ABSTRACT The overuse and misuse of antibiotics in clinical settings and in food production have been linked to the increased prevalence and spread of antimicrobial resistance (AR). Consequently, public health and consumer concerns have resulted in a remarkable reduction in antibiotics used for food animal production. However, there are no data on the effectiveness of antibiotic removal in reducing AR shared through horizontal gene transfer (HGT). In this study, we used neonatal broiler chicks and Salmonella enterica serovar Heidelberg, a model food pathogen, to test if chicks raised antibiotic free harbor transferable AR. We challenged chicks with an antibiotic-susceptible S . Heidelberg strain using various routes of inoculation and determined if S . Heidelberg isolates recovered carried plasmids conferring AR. We used antimicrobial susceptibility testing and whole-genome sequencing (WGS) to show that chicks grown without antibiotics harbored an antimicrobial resistant S . Heidelberg population at 14 days after challenge and chicks challenged orally acquired AR at a higher rate than chicks inoculated via the cloaca. Using 16S rRNA gene sequencing, we found that S . Heidelberg infection perturbed the microbiota of broiler chicks, and we used metagenomics and WGS to confirm that a commensal Escherichia coli population was the main reservoir of an IncI1 plasmid acquired by S . Heidelberg. The carriage of this IncI1 plasmid posed no fitness cost to S . Heidelberg but increased its fitness when exposed to acidic pH in vitro . These results suggest that HGT of plasmids carrying AR shaped the evolution of S . Heidelberg and that antibiotic use reduction alone is insufficient to limit antibiotic resistance transfer from commensal bacteria to Salmonella enterica . IMPORTANCE The reported increase in antibiotic-resistant bacteria in humans has resulted in a major shift away from antibiotic use in food animal production. This shift has been driven by the assumption that removing antibiotics will select for antibiotic susceptible bacterial taxa, which in turn will allow the currently available antibiotic arsenal to be more effective. This change in practice has highlighted new questions that need to be answered to assess the effectiveness of antibiotic removal in reducing the spread of antibiotic resistance bacteria. This research demonstrates that antibiotic-susceptible Salmonella enterica serovar Heidelberg strains can acquire multidrug resistance from commensal bacteria present in the gut of neonatal broiler chicks, even in the absence of antibiotic selection. We demonstrate that exposure to acidic pH drove the horizontal transfer of antimicrobial resistance plasmids and suggest that simply removing antibiotics from food animal production might not be sufficient to limit the spread of antimicrobial resistance. 
    more » « less
  5. Vives, Martha (Ed.)
    ABSTRACT Phage Felix O1 (FO1) is one of the most widely used bacteriophages for targetingSalmonella entericaand is applied in both research and food safety settings. Despite its broad host range, we observed significantly reduced efficiency of plating (EOP) on a subset ofSalmonella entericastrains, including serovar Typhimurium 4/74 (S. 4/74). We found that O-antigen–mediated steric hindrance contributes to this resistance, which can be partially overcome by supplementation with the SP6 phage tailspike protein (TSP). However, full restoration of the EOP required deletion of the Gifsy-1 prophage, leading to the identification of a single prophage-encoded defense gene,gipd474(Gifsy-encoded phage defense protein from strainS. 4/74). Heterologous expression of this gene inEscherichia coliincreased resistance to multiple tailed phages. Bioinformatic analysis revealed that this gene is widely spread across theEnterobacteriaceae, suggesting a conserved role in phage resistance. Together, these findings uncover a dual barrier to FO1 infectivity inS. 4/74 and highlightgipd474as a novel, prophage-encoded phage defense gene.IMPORTANCEPhage therapy and biocontrol are increasingly explored as alternatives to antibiotics, particularly against drug-resistant pathogens such asSalmonella. FO1 is a widely used lytic phage with broad activity acrossSalmonellaserotypes. However, variability in phage infectivity limits its reliability against certain strains. Here, we report thatS. 4/74 restricts FO1 through a combination of O-antigen–associated interference and a novel prophage-encoded resistance gene. This gene also impairs the infectivity of other tailed phages and is conserved across multipleEnterobacteriaceaegenera. Our findings highlight the importance of prophage-encoded defense systems in shaping phage susceptibility and highlight the need to account for such elements when developing phage-based applications. 
    more » « less