Investigating bacterial ribosomal sequence variation in regards to future structural and antibiotic research.

Ribosome-targeting antibiotics comprise over half of antibiotics used in medicine, but our fundamental knowledge of their binding sites is derived primarily from ribosome structures from non-pathogenic species. These include Thermus thermophilus, Deinococcus radiodurans and Haloarcula marismortui, as well as the commensal or pathogenic Escherichia coli. Advancements in electron cryomicroscopy have allowed for the determination of more ribosome structures from pathogenic bacteria, with each study highlighting species-specific differences that had not been observed in the non-pathogenic structures. These observed differences suggest that more novel ribosome structures, particularly from pathogens, are required to get a more accurate understanding of the level of diversity in the bacterial ribosome, leading to potential advancements in antibiotic research. In this study, covariance and hidden Markov models were used to annotate ribosomal RNA and protein sequences respectively from genomic sequence, allowing us to determine the underlying ribosomal sequence diversity using phylogenetic methods. This analysis provided evidence that the current non-pathogenic ribosome structures are not sufficient representatives of some pathogenic bacteria, such as Campylobacter pylori, or of whole phyla such as Bacteroidetes.

New Study: Helicobacter Species as a Potential Zoonotic Infectious Carcinogen : A Review

In 1983 two Australian doctors discovered a spiral bacterium in the human stomach which was called Campylobacter pylori (or pyloridis) to be re-named (Helicobacter pylori) in 1990. Carried by half the global population it was first believed exclusive to Human causing chronic gastritis, peptic and duodenal ulcer, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. This discovery revolutionized peptic ulcer treatment with antibiotics instead of surgery. H.pylori is the only bacterial agent classified as Class 1 carcinogen. In 1997 genetic advances allowed genome sequencing and detailed research particularly on genomic pathogenesis. Genome printing methods revealed that H.pylori was transmitted from domesticated animals to pre-stone-age man probably of African ancestry. New non-pylori Helicobacter species were found in farm, small, wild, and non-human primate animals. Some cause chronic gastritis and vomiting, occasionally lymphocytic gastric tissue proliferation and cancer. Some animal and avian species are contagious to human, sometimes sharing genomic similarities with H.pylori. There are currently about 35 Helicobacter species. In pathogenic strains, certain genes function as virulence factors making proteins responsible for chronic inflammatory reactions and carcinogenesis in variable degrees. This is called (genomic polymorphism), it create diverse species and strains with variable degrees of pathogenicity. Genomic heterogeneity is the result of Helicobacter adaptation in various environmental, geographic, and host circumstances. Helicobacter strains with diverse virulence may exist in different ethnic and geographic groups. Both H.pylori in human and non-pylori species in animal may co-exist mixed in one host. Sheep is believed the reservoir for H.pylori and H.canis.

Theory of Additional Corpus Biopsy for Epidemiology and Diagnosis of Helicobacter Pylori

Background: There is still debate on the best sites for biopsy- based tests of Helicobacter pylori infection in patients with gastritis. This study was designed to determine if it is important to add corpus biopsies to the routine antral ones for identification of H. pylori, especially in case of gastric atrophy and/or intestinal metaplasia. Methods: A causative role is now accepted for Helicobacter (formerly Campylobacter) pylori in type B gastritis, and evidence is accumulating that H. pylori infection plays a major contributory role in peptic ulcer disease. Preliminary studies have reported that the prevalence of H pylori infection increases with age, but detailed information on the prevalence of the bacteria in any defined population and on the factors that may influence the pattern of distribution remains scanty. Results: Up to 85% of people infected with H. pylori never experience symptoms or complications. Acute infection may appear as an acute gastritis with abdominal pain (stomach ache) or nausea. Where this develops into chronic gastritis, the symptoms, if present, are often those of nonulcer dyspepsia: stomach pains, nausea, bloating, belching, and sometimes vomiting or black stool. Conclusion: H. pylori has been associated with colorectal polyps and colorectal cancer. It may also be associated with eye disease.

Bocepreviralapú hármas kezelés hatékonyságának és biztonságosságának retrospektív elemzése előrehaladott fibrosisstádiumú, hepatitis C-vírus 1-es genotípussal fertőzött, korábban sikertelenül kezelt magyar betegeknél

Introduction: During 2011 and 2013, 155 Hungarian hepatitis C genotype 1 infected patients, mostly with advanced liver fibrosis, who did not respond to prior peginterferon + ribavirin dual therapy, started boceprevir based triple therapy in an early access program. Aim and method: Efficacy and safety of the therapy was retrospectively assessed based on sustained virologic responses, as well as on frequency and type of serious adverse events and of those leading to therapy discontinuation. Results: In an intent-to-treat analysis 39.4% patients (61/155) reached sustained virologic response. Amongst pervious relapsers, partial responders and null-responders 59.5%, 41.4 % and 22.9% (p<0.05 compared to the other two categories) reached sustained virologic response, respectively, while amongst non-cirrhotics and cirrhotics 52.5% and 31.3% (p<0.05 compared to the non-cirrhotics) achieved sutained virologic response, respectively. Six out of the 33 most difficult to cure patients (previous null responder and cirrhotic) have reached sustained virologic response (18.2%). Frequency of early discontinuations due to insufficient virologic response was 31.1%, while due to adverse event 10.3%. Reported frequency of serious adverse event was 9.8%. These events represented anemia, diarrhoea, depression, agranulocytosis, elevated aminotransferases, generalized dermatitis and severe gingivitis with loss of teeth, prolonged QT interval on ECG, generalized oedema and severe dyspnoea, uroinfection, exacerbation of Crohn’s disease, Campylobacter pylori infection and unacceptable weakness and fatigue. Eight patients received transfusion, 4 patients erythropoietin and 1 granulocyte colony stimulating factor during therapy. No death has been reported. Conclusions: With boceprevir based triple therapy, one of the bests available in 2011–2013 in Hungary, a relevant proportion of hepatitis C infected patients with advanced liver fibrosis achieved sustained viral response. In this cohort, side-effects resembled those reported in registration studies, and resulted in therapy discontinuation with consequent treatment failure in a relevant number of patients. Efficacy and tolerability of boceprevir-based triple therapy are suboptimal, particularly in the most difficult to cure patient population. Orv. Hetil., 2016, 157(34), 1366–1374.