Phytochemicals of Aloe barbadensis miller as Potential Inhibitors of Uropathogenic Escherichia coli for Urinary Tract Infection Therapy: An in Silico Approach

Urinary tract infections (UTIs) are common infections caused by normal skin or rectum bacteria that get into the urethra and infect the urinary tract. Although the infection can affect various parts of the tract, bladder infections are the most prevalent kind. Uropathogenic Escherichia Coli (UPEC) is the most common pathogen associated with UTI development. Therefore, inhibiting the UPEC protein target (PDB ID: 8BVD) appears to be a promising therapeutic strategy. Therefore, in this study, molecular docking and dynamics were conducted to examine the antibacterial activity of Aloe barbadensis miller against UPEC bacteria. The Aloe barbadensis miller natural compounds licochalcone A, palmidin B and palmidin C were downloaded from PubChem with amoxicillin, which was used as a control drug and studied against the target molecule. The potential parameters examined were the docking scores, absorption, distribution, metabolism, excretion, toxicity (ADMET), bioavailability, root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, radius of gyration, and potential energy of the system. Docking scores showed that all ligands demonstrated an admirable candidature as an inhibitor to 8BVD molecule, and the score hierarchy is licochalcone A (-6.4 kcal/mol), palmidin C (-6.1 kcal/mol), palmidin B (-6.0 kcal/mol), and amoxicillin (-5.9 kcal/mol). All ligands appeared to have good drug-like properties and oral bioavailability. Molecular dynamic studies showed that all ligands exhibited an excellent nominee as inhibitors in their vicinity at 20 ns. However, there is a relatively high fluctuation of palmidin B compared with other compounds, which seems to be more stable. This work suggests that the selected phytoconstituents could be used as inhibitors of the 8BVD protein in the fight against UTIs. However, further investigation on the clinical and experimental validation of UTI treatment’s specific mechanisms and effects is still welcomed.

Genetic Diversity of Uropathogenic Escherichia coli Isolated from Human T Lymphotropic Virus Type I (HTLV-I) Infected Individuals

Urinary tract infection (UTI) is a frequent pathology among HTLV-I+ individuals being capable of severely compromising the kidneys and bladder. Molecular characteristics of uropathogenic Escherichia coli (UPEC) from HTLV-I+ infected individuals are unknown. UPEC isolates from HTVL-I+ individuals, with and without clinical symptoms of myelopathy, were submitted to genetic typing seeking to infer bacterial diversity and potential virulence. 71 bacterial isolates were characterized according to random amplified polymorphic DNA and phylotypes. Phylotyping classified E. coli into four phylogenetic groups: A (18.3%), B1 (16.9%), B2 (39.4%), and D (25.3%) and 8 phylotypes according to the presence of the genetic sequences chuA, yjaA and the DNA fragment TSPE4.C2: ﹣﹣﹣ (5.6%) and ﹣+﹣ (12.6%) in phylogroup A, ﹣﹣+ (7.0%) and ﹣++ (9.8%) in B1, +++ (32.3%) and ++﹣ (7.0%) in B2, +﹣﹣ (15.4%) and +﹣+ (9.8%) in D. The B2 phylogroup was the most prevalent among HTLV﹣ associated myelopathy and asymptomatic individuals. RAPD-PCR typing revealed a high degree of bacterial polymorphism indicating a non-clonal origin. Genotypes were not found to be distributed according to clinical status or epidemiological features. Our results lead us to suggest that the neurological impairment in HTLV-I+ individuals can be a risk factor for urinary infections due E. coli which are caused by distinct bacterial lineages.

Multi-drug Resistant Uropathogenic Escherichia coli and Its Treatment by Chinese Medicine

Objectives： To investigate the resistance and virulence profiles of uropathogenic Escherichia coli（UPEC） and its treatment by Chinese medicine（CM） Fuzheng Qingre Lishi Formula（扶正清热利湿方, FQLF）. Methods： UPEC strains were isolated from recurrent urinary tract infections（UTIs） patients. Patient sensitivities to 17 antibiotics were tested by the disk diffusion method. Virulence genes were screened by plolymerase chain reaction. A mouse model was constructed using a multi-drug resistant and virulent UPEC strain and treated with FQLF or the antibiotic imipenem. The treatment efficacy was evaluated by bacterial clearance from urine and the urinary organs. Results： A total of 90 UPEC strains were collected, and 94.4% of the isolates were resistant to at least 1 antibiotic. Approximately 66.7% of the UPEC strains were multi-drug resistant. More than one virulence gene was found in 85.6% of the isolates. The extended-spectrum β-lactamases（ESBL）-positive strains were more resistant than the negative ones. The virulence gene number was positively correlated with the resistance number（P〈0.05）. A mouse model was successful y constructed using UPEC10. Treatment with either FQLF or antibiotics significantly cleared bacteria from the mouse urine after 14 days. In the untreated control, the bacteria lasted for 28 days. FQLF treatment of the UTI mouse model greatly reduced the bacterial number in the kidney and bladder, but could not completely clear the bacteria. Conclusions： Multi-drug resistance is common among UPEC isolates, and the resistance is positively related with virulence. FQLF could treat UPEC UTIs, but could not completely clear the bacteria from the host.

Prevalence of ESBL phenotype,bla_(CTX-M-1),bla_(SHV)and bla_(TEM)genes among uropathogenic Escherichia coli isolates from 3 military hospitals of Tehran,Iran

Objective:To determine the extended-spectrum beta-lactamase(ESBL)production and prevalence of bla_(CTX-M-1),bla_(SHV)and bla_(TEM)genes among uropathogenic Escherichia coli(UPEC)isolates from 3 military hospitals of Tehran during 2015-2016.Methods:One-hundred and eleven isolates were adopted.The antibiotic susceptibility testing was conducted according to Clinical and Laboratory Standards Institute guidelines.The combine disk was used for phenotypic ESBL production.The ceftazidime MIC was conducted with the micro-broth dilution test.The PCR assay was used to detect the bla_(CTX-M-1),bla_(SHV)and bla_(TEM)genes.Results:In the broth microdilution method,103(92.7%)isolates showed minimal inhibitory concentration(MIC)≥1μg/mL,and also in the combined disk method,89(80.1%of all)were ESBL positive.On the other hand,among 91 ceftazidime resistant isolates,86(77.4%of all)were ESBL positive.The difference between the two methods for ESBL confirmation was not significant.The result of MIC was similar to the disk diffusion method in the detection of phenotypic ESBL production.Among ESBL producer isolates,the prevalence of bla_(CTX-M-1),bla_(SHV)and bla_(TEM)was 77.4%(n=86),47.4%(n=53)and 2.4%(n=2),respectively.These genes were amplified in a wide range MIC of ceftazidime.Conclusions:The prevalence of multi-drug resistant UPEC and ESBL positive isolates was high in military hospitals.The majority of UPEC isolates amplified bla_(CTX-M-I)and bla_(SHV)typeβ-lactamase genes.One-third of isolates were positive in presence of both these genes.There was no relation between ceftazidime MIC and presence of beta-lactamase genes.