scholarly journals Liposomal-lipopolysaccharide vaccine extracted from Proteus mirabilis induces moderate TLR4 and CD14 production

2019 ◽  
Vol 32 (2) ◽  
pp. 81-86
Author(s):  
Ruaa SH. Nile ◽  
Mayyada F. Darweesh ◽  
Mohauman M. Al-Rufaie

Abstract Proteus mirabilis is a common cause of recurrent urinary tract infections in individuals with functional or structural abnormalities. It also forms bladder and kidney stones. Lipopolysaccharide (LPS) is a potential Proteus virulence factor that plays a key role in pathogenesis, as well as in stimulating innate immune response. Therefore, this study aimed to extract LPS from a highly resistant isolate and incorporate it in a delivery system (liposome) to stimulate an immune response against virulent pathogens. In the work, 50 isolates of P. mirabilis were taken from 200 urine specimens obtained from recurrent-urinary tract infections (UTI) of patients of AL-Sadar Hospital. Specimens were cultured on specific media, and then bacterial isolates were identified via morphological, biochemical and Vitek-2 systems. The results showed that P. mirabilis was expressed in 11 (22%), 30 (60%) and 9 (18%) recurrent UTI, kidney stone and catheter samples, respectively. All isolates were assessed through antibiogram testing, with the results revealing that most isolates were multidrug resistant to more than 3 classes of antibiotics. Herein, P. mirabilis NO 50 revealed particularly high resistance, so it was chosen for LPS extraction. Lethal dose 50 (LD50) observations indicated that a live suspension of P. mirabilis was at 4.5×107 CFU/ml, while LPS was at 270 μg/ml. LPS was used as an immunogenic to stimulate the immune system through injecting Rats intraperitoneally (I.P.) with 1 ml of LD50%. Subsequently, the efficiency of immunogenes in stimulating the immune response was evaluated by determining the Toll-like receptor and CD14 levels. The results indicate that LPS incorporated in the Liposome released moderate levels of Toll-like receptors-4 (TLR4) that enabled the immune system to clear pathogens. The LPS+ complete Freund’s adjuvant (CFA) and LPS vaccinated groups recorded hyper production for TLR4 (52.2 and 40.9 pg/ml, respectively), this was followed by liposome (LIP) and bacterial suspension (11 and 20.5 pg/ml, respectively) in ranking effectiveness. This study reveals a mean of CD14 that was higher in both LPS and LPS+CFA and moderate in LPS+LIP, in comparison with control and liposome groups. In conclusion, LPS-Liposomes are a promising nanomedicine for modulating the hyper response of LPS. This may lead to tissue inflammation but appeared beneficial in stimulating the immune response at moderate levels so as to eradicate infection without tissue damage.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S823-S823
Author(s):  
Kendra Foster ◽  
Linnea A Polgreen ◽  
Brett Faine ◽  
Philip M Polgreen

Abstract Background Urinary tract infections (UTIs) are one of the most common bacterial infections. There is a lack of large epidemiologic studies evaluating the etiologies of UTIs in the United States. This study aimed to determine the prevalence of different UTI-causing organisms and their antimicrobial susceptibility profiles among patients being treated in a hospital setting. Methods We used the Premier Healthcare Database. Patients with a primary diagnosis code of cystitis, pyelonephritis, or urinary tract infection and had a urine culture from 2009- 2018 were included in the study. Both inpatients and patients who were only treated in the emergency department (ED) were included. We calculated descriptive statistics for uropathogens and their susceptibilities. Multi-drug-resistant pathogens are defined as pathogens resistant to 3 or more antibiotics. Resistance patterns are also described for specific drug classes, like resistance to fluoroquinolones. We also evaluated antibiotic use in this patient population and how antibiotic use varied during the hospitalization. Results There were 640,285 individuals who met the inclusion criteria. Females make up 82% of the study population and 45% were age 65 or older. The most common uropathogen was Escherichia Coli (64.9%) followed by Klebsiella pneumoniae (8.3%), and Proteus mirabilis (5.7%). 22.2% of patients were infected with a multi-drug-resistant pathogen. We found that E. Coli was multi-drug resistant 23.8% of the time; Klebsiella pneumoniae was multi-drug resistant 7.4%; and Proteus mirabilis was multi-drug resistant 2.8%. The most common antibiotics prescribed were ceftriaxone, levofloxacin, and ciprofloxacin. Among patients that were prescribed ceftriaxone, 31.7% of them switched to a different antibiotic during their hospitalization. Patients that were prescribed levofloxacin and ciprofloxacin switched to a different antibiotic 42.8% and 41.5% of the time, respectively. Conclusion E. Coli showed significant multidrug resistance in this population of UTI patients that were hospitalized or treated within the ED, and antibiotic switching is common. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 9 (7) ◽  
pp. 1416
Author(s):  
Karen Leth Nielsen ◽  
Marc Stegger ◽  
Kristoffer Kiil ◽  
Berit Lilje ◽  
Karen Ejrnæs ◽  
...  

Recurrent urinary tract infection (rUTI) remains a major problem for many women and therefore the pursuit for genomic and phenotypic traits which could define rUTI has been ongoing. The present study applied a genomic approach to investigate recurrent urinary tract infections by comparative analyses of recurrent and non-recurrent Escherichia coli isolates from general practice. From whole-genome sequencing data, phylogenetic clustering and genomic traits were studied on a collection of isolates which caused recurrent infection compared to non-recurrent isolates. In addition, genomic variation between the 1st and following infection was studied on a subset of the isolates. Evidence of limited adaptation between the recurrent infections based on single nucleotide polymorphism analyses with a range of 0–13 non-synonymous single nucleotide polymorphisms (SNPs) between the paired isolates. This included an overrepresentation of SNPs in metabolism genes. We identified several genes which were more common in rUTI isolates, including nine fimbrial genes, however, not significantly after false-discovery rate. Finally, the results show that recurrent isolates of the present dataset are not distinctive by variation in the core genome, and thus, did not cluster distinct from non-rUTI isolates in a SNP phylogeny.


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