Point Mutations at gyrA and gyrB Genes of Levofloxacin Resistant Helicobacter pylori Strains and Dual Resistance with Clarithromycin.

BACKGROUND: Spontaneous point mutations in genes encoding gyrA/B subunits of DNA gyrase are responsible for fluoroquinolone resistance. We aimed to determine the clarithromycin and levofloxacin resistance phenotypically in H. pylori strains and to investigate the mutations responsible for levofloxacin resistance and the effects of these mutations on dual antibiotic resistance. METHODS: A total of 65 H. pylori isolates were included. The E-test method was used for the clarithromycin and le-vofloxacin antimicrobial susceptibility test. Real-time PCR was used to detect the point mutations. RESULTS: Twenty-four (36.9%) of 65 H. pylori strains were phenotypically resistant to clarithromycin and 14 (21.5%) to levofloxacin. The phenotypic levofloxacin resistance rate of strains with Asn87Lys and Asp91Asn mutations were significantly higher (gyrA gene) (p < 0.05). The phenotypic levofloxacin resistance rate of strains with Arg484Lys and Asp481Glu mutations were significantly higher (gyrB gene) (p < 0.05). The Asn87Lys mutation increased the risk of phenotypes being resistant to levofloxacin 70.156 times and Asp91Asn mutation increased 125,427 times higher. Seven (10.8%) of 65 H. pylori strains showed dual resistance to both levofloxacin and clarithromycin. The rate of being dual resistant with A2143G mutation (clarithromycin resistance) was found to be significantly higher (p < 0.05). CONCLUSIONS: The Asn87Lys and Asp91Asn mutations in the gyrA gene had a phenotypically enhancing effect on levofloxacin resistance, while the presence of Asp481Glu and Arg484Lys mutations in the gyrB gene did not. The existence of dual resistance was developed with the increase in clarithromycin and levofloxacin resistance rates.

Papel del factor neurotrófico de origen cerebral y de la neurotropina-3 en la relación de Chlamydophila pneumoniae con la esquizofrenia / The relationship of Chlamydophila pneumoniae with schizophrenia: The role of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in this relationship

Several pathogens have been suspected of playing a role in the pathogenesis of schizophrenia. Chronic inflammation has been proposed to occur as a result of persistent infection caused by Chlamydophila pneumoniae cells that reside in brain endothelial cells for many years. It was recently hypothesized that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) may play prominent roles in the development of schizophrenia. NT-3 and BDNF levels have been suggested to change in response to various manifestations of infection. Therefore, we aimed to elucidate the roles of BDNF and NT3 in the schizophrenia-C. pneumoniae infection relationship. RT-PCR, immunofluorescence and ELISA methods were used. Fifty patients suffering from schizophrenia and 35 healthy individuals were included as the patient group (PG) and the healthy control group (HCG), respectively. We detected persistent infection in 14 of the 50 individuals in the PG and in 1 of the 35 individuals in the HCG. A significant difference was found between the two groups (p < 0.05). Twenty-two individuals in the PG and 13 in the HCG showed seropositivity for past C. pneumoniae infection, and no difference was observed between the groups (p > 0.05). C. pneumoniae DNA was not detected in any group. A significant difference in NT-3 levels was observed between the groups, with very low levels in the PG (p < 0.001). A significant difference in BDNF levels was also found, with lower levels in the PG (p < 0.05). The mean serum NT-3 level was higher in the PG cases with C. pneumoniae seropositivity than in seronegative cases; however, this difference was not statistically significant (p > 0.05). In conclusion, we suggest that NT-3 levels during persistent C. pneumoniae infection may play a role in this relationship.

Existe la sospecha de que algunos patógenos pueden desempeñar un papel en la patogénesis de la esquizofrenia; en ese contexto, se ha propuesto que la infección persistente causada por células de Chlamydophila pneumoniae presentes en las células endoteliales cerebrales durante muchos años lleva a la inflamación crónica. Recientemente se ha planteado la hipótesis de que el factor neurotrófico de origen cerebral (BDNF, por sus siglas en inglés) y la neurotropina-3 (NT-3) podrían estar implicados en el desarrollo de la esquizofrenia, y se ha sugerido que sus niveles se modifican en respuesta a diversas manifestaciones de la infección. En esta investigación intentamos esclarecer el papel que desempeñan el BDNF y la NT3 en la relación entre la esquizofrenia y la infección por C. pneumoniae. Se utilizaron métodos de RT-PCR, inmunofluorescencia y ELISA. Se incluyeron 50 pacientes con esquizofrenia y 35 individuos sanos como grupo de pacientes (GP) y grupo de controles sanos (GCS), respectivamente. Detectamos una infección persistente en 14 sujetos del GP y en 1 de los del GCS, lo que constituyó una diferencia significativa (p < 0,05). Veinte participantes del GP y 13 del GCS fueron seropositivos para una infección pasada por C. pneumoniae, diferencia no significativa (p > 0,05). No se detectó ADN de C. pneumoniae en ninguno de los dos grupos. Se observó una diferencia significativa entre los grupos en los niveles de NT-3, que fueron muy bajos en el GP (p < 0,001), y de BDNF, inferiores en el GP (p < 0,05). La concentración sérica media de NT-3 fue mayor en los individuos seropositivos para C. pneumoniae en comparación con los seronegativos, pero esta diferencia no alcanzó significación estadística (p > 0,05). Sugerimos que los niveles de NT-3 durante una infección persistente por C. pneumoniae pueden estar implicados en la relación de Chlamydophila pneumoniae con la esquizofrenia.