Prevalence of heteroresistant Helicobacter pylori and treatment follow-up in patients in Ilam, Iran.

Background: Special antibiotics are prescribed against Helicobacter (H.) pylori. However, sometimes the bacteria are not completely eliminated, or they are recurrent. Unlike most infections, it is very difficult to eliminate a H. pylori infection. Heteroresistance is defined as the phenomenon in which subpopulations of the same colony of bacteria exhibit a range of susceptibilities to a particular antibiotic. Because of heteroresistant cells, antibiotic failure and chronic infection can occur; thus, the current research aimed to investigate presence of heteroresistant cells in H. pylori collected from patients reffering to clinic in Ilam, Iran. Subsequently, patients who were infected with heteroresistant H. p ylori were treated with antibiotics effective against heteroresistant subpopulations. Methods: In this cross-sectional descriptive study, 100 patients with clinical symptoms and suspected of being infected with H. pylori were studied in private clinics in Ilam, Iran. Fiftyisolates of H. pylori accompanied by patients' information were obtained from Ilam clinics. We cultured the bacteria to identify heteroresistance and to find the cause of recurrent infection in these patients. Results: Out of a total of 50 samples, 3 were heteroresistant to clarithromycin (6%). Levofloxacin was applied in cases of heteroresistant samples, and the effectiveness was determined after one month of follow-up of patients. Conclusion: Patients with heteroresistance showed sensitivity to levofloxacin. After one month of follow-up, it was found that the effectiveness of this antibiotic was good. Therefore, this antibiotic was introduced as a more effective drug in patients with heteroresistant H. pylori.

Biomaterial engineering strategies for B cell immunity modulations.

B cell immunity has a penetrating effect on human health and diseases. Therapeutics aiming to modulate B cell immunity have achieved remarkable success in combating infections, autoimmunity, and malignancies. However, current treatments still face significant limitations in generating effective long-lasting therapeutic B cell responses for many conditions. As the understanding of B cell biology has deepened in recent years, clearer regulation networks for B cell differentiation and antibody production have emerged, presenting opportunities to overcome current difficulties and realize the full therapeutic potential of B cell immunity. Biomaterial platforms have been developed to leverage these emerging concepts to augment therapeutic humoral immunity by facilitating immunogenic reagent trafficking, regulating T cell responses, and modulating the immune microenvironment. Moreover, biomaterial engineering tools have also advanced our understanding of B cell biology, further expediting the development of novel therapeutics. In this review, we will introduce the general concept of B cell immunobiology and highlight key biomaterial engineering strategies in the areas including B cell targeted antigen delivery, sustained B cell antigen delivery, antigen engineering, T cell help optimization, and B cell suppression. We will also discuss our perspective on future biomaterial engineering opportunities to leverage humoral immunity for therapeutics.

Novel Antimicrobial Target in Acinetobacter Baumannii.

BACKGROUND: Resistance to multiple drugs is one of the biggest challenges in managing infectious diseases. Acinetobacter baumannii is considered a nosocomial infection. According to the multiple roles of the toxin-antitoxin system, this system can be considered an antimicrobial target in the presence of bacteria. With the impact on bacterial toxin, it can be used as a new antibacterial target. The purpose of this study was to determine the mazEF genes as a potent antimicrobial target in A. baumannii clinical isolates. METHODS: The functionality of mazEF genes was evaluated by qPCR in fifteen A. baumannii clinical isolates. Then, the mazE locus was targeted by peptide nucleic acid (PNA). RESULTS: The results showed a significant difference in the mean number of copies of mazF gene in normal and stress conditions. Also, we found that at a concentration of 15 µM of PNA the bacteria were killed and confirmed by culture on LB agar. CONCLUSIONS: This research is the first step in introducing mazEF TA loci as a sensitive target in A. baumannii. However, more studies are needed to test the effectiveness in vivo. In addition, the occurrence and potential for activation of the TA system, mazEF in other pathogenic bacteria should be further investigated.

relBE toxin-antitoxin system as a reliable anti-biofilm target in Pseudomonas aeruginosa.

AIMS: The ability of the pathogenic bacterium Pseudomonas aeruginosa to produce biofilms has made it more difficult to treat its infections with current antibiotics. Several genes are involved in biofilm production, and toxin-antitoxin (TA) loci have been reported to be responsible for the regulation of biofilm-associated genes. This study was aimed at evaluating various TA loci in P. aeruginosa to find a reliable target in order to disrupt biofilm formation. METHODS AND RESULTS: Thirty clinical isolates of P. aeruginosa were assessed for biofilm production as well as the presence of various TA loci in their genomes. The relBETA locus was present in all 30 P. aeruginosa isolates but its expression was not detectable in isolates that did not show biofilm production. Quantitative real-time -PCR (q-PCR) also demonstrated that the expression of relBE was higher in isolates with stronger biofilm-producing capability. Knocking out the relBE locus in one biofilm-producing P. aeruginosa isolate led to the cessation of biofilm-producing capacity in that isolate and eliminated the expression of ndvB, which is among the genes involved in biofilm production. CONCLUSIONS: These results inferred the involvement of relBE TA locus in the regulation of biofilm production in P. aeruginosa and indicated the possibility of relBE as an anti-biofilm target for this pathogen.

Persister cells as a possible cause of antibiotic therapy failure in Helicobacter pylori.

BACKGROUND AND AIM: Due to the failure of antibiotic treatment and recurrence of infection in patients with Helicobacter pylori, this study was designed to find the possible cause of treatment failure and recurrence of the H. pylori infections in Ilam, Iran. METHODS: One hundred patients with specific symptoms of H. pylori infection were selected, and after taking a biopsy specimen, identification of H. pylori, antibiotic susceptibility assay, and persister cell assay were performed. In addition, after treatment, patients with persister cells were followed for possible recurrence of infection. Furthermore, an antibiotic susceptibility assay was performed. RESULTS: Our results demonstrated that, among 100 patients, 50% (n = 50) showed positive results for the existence of H. pylori. Among the susceptible isolates, 18% (n = 9) were persister cells that were sensitive to clarithromycin as confirmed by a 5 folds higher than the Minimal Inhibitory Concentration (MIC) of clarithromycin. The data were confirmed by following up the suspected patients. CONCLUSION: Our results demonstrated that persister cells in H. pylori infections may be responsible to recurrent infection and antibiotic treatment failure. However, more research is needed to obtain more information in this area.

Short-term MRI measurements as predictors of EDSS progression in relapsing-remitting multiple sclerosis: grey matter atrophy but not lesions are predictive in a real-life setting.

BACKGROUND: Magnetic resonance imaging (MRI) is the best biomarker of inflammatory disease activity in relapsing remitting Multiple Sclerosis (RRMS) so far but the association with disability is weak. Appearance of new MRI-lesions is used to evaluate response to immunotherapies in individual patients as well as being the most common primary outcome in phase-2 trials. Measurements of brain atrophy show promising outcomes in natural cohort studies and some phase-2 trials. From a theoretical perspective they might represent irreversible neurodegeneration and be more closely associated with disability. However, these atrophy measurements are not yet established as prognostic factors in real-life clinical routine. High field MRI has improved image quality and resolution and new methods to measure atrophy dynamics have become available. OBJECTIVE: To investigate the predictive value of MRI classification criteria in to high/low atrophy and inflammation groups, and to explore predictive capacity of two consecutive routine MRI scans for disability progression in RRMS in a real-life prospective cohort. METHODS: 82 RRMS-patients (40 untreated, 42 treated with immunotherapies, mean age 40 years, median Expanded Disability Status Scale (EDSS) of 2, underwent two clinically indicated MRI scans (3 Tesla) within 5-14 months, and EDSS assessment after a mean of 3.0 (1.5-4.2) years. We investigated the predictive value of predefined classifications in low/high inflammatory and atrophy groups for EDSS progression (≥1.5 if baseline EDSS = 0, ≥1.0 if baseline EDSS <5, ≥0.5 for other) by chi-square tests and by analysis of variance (ANOVA). The classifications were based on current scientific or clinical recommendation (e.g., treatment response criteria). Brain atrophy was assessed with three different methods (SIENA, SIENAX, and FreeSurfer). Post-hoc analyses aimed to explore clinical data and dynamics of MRI outcomes as predictors in multivariate linear and logit models. RESULTS: Progression was observed in 24% of patients and was independent from treatment status. None of the predefined classifications were predictive for progression. Explorative post-hoc analyses found lower baseline EDSS and higher grey matter atrophy (FreeSurfer) as best predictors (R (2) = 0.29) for EDSS progression and the accuracy was overall good (Area under the curve = 0.81). CONCLUSION: Beside EDSS at baseline, short-term grey matter atrophy is predictive for EDSS progression in treated and untreated RRMS. The development of atrophy measurements for individual risk counselling and evaluation of treatment response seems possible, but needs further validation in larger cohorts. MRI-atrophy estimates from the FreeSurfer toolbox seem to be more reliable than older methods.