stg fimbrial operon from S. Typhi STH2370 contributes to association and cell disruption of epithelial and macrophage-like cells

BACKGROUND: Salmonella enterica serovar Typhi (S. Typhi) stg operon, encoding a chaperone/usher fimbria (CU), contributes to an increased adherence to human epithelial cells. However, one report suggests that the presence of the Stg fimbria impairs the monocyte-bacteria association, as deduced by the lower level of invasion to macrophage-like cells observed when the stg fimbrial cluster was overexpressed. Nevertheless, since other CU fimbrial structures increase the entry of S. Typhi into macrophages, and considering that transcriptomic analyses revealed that stg operon is indeed expressed in macrophages, we reassessed the role of the stg operon in the interaction between S. Typhi strain STH2370 and human cells, including macrophage-like cells and mononuclear cells directly taken from human peripheral blood. RESULTS: We compared S. Typhi STH2370 WT, a Chilean clinical strain, and the S. Typhi STH2370 Astg mutant with respect to association and invasion using epithelial and macrophage-like cells. We observed that deletion of stg operon reduced the association and invasion of S. Typhi, in both cellular types. The presence of the cloned stg operon restored the WT phenotype in all the cases. Moreover, we compared Salmonella enterica sv. Typhimurium 14028s (S. Typhimurium, a serovar lacking stg operon) and S. Typhimurium heterologously expressing S. Typhi stg. We found that the latter presents an increased cell disruption of polarized epithelial cells and an increased association in both epithelial and macrophage-like cells. CONCLUSIONS: S. Typhi stg operon encodes a functional adhesin that participates in the interaction bacteria-eukary-otic cells, including epithelial cells and macrophages-like cells. The phenotypes associated to stg operon include increased association and consequent invasion in bacteria-eukaryotic cells, and cell disruption.

Drug utilization review of ciprofloxacin in the outpatient department of Boru Meda Hospital, South Wollo Zone, Amhara Region, Ethiopia.

Background: The antimicrobial agents developed during the last 60 years are among the most dramatic examples of the advances of modern medicine. Many infectious diseases once considered incurable and lethal are now amenable to treatment with a few pills. They are among the most frequently prescribed medications to day although microbial resistance due to evolutionary and misuse threatens their continued efficacy. One mechanism to ensure correct prescribing and use is drug use evaluations studies. Objective of current study is to evaluate retrospectively of ciprofloxacin use from outpatient medical records by using pre- set criteria in Boru Meda hospital. Methods: A cross-sectional study on retrospectively collected data was used to evaluate ciprofloxacin use from outpatient medical history records existing from January 18, 2009 to January 17, 2010. Criteria along with thresholds set by experts for undertaking drug use evaluation for ciprofloxacin was used which is modified based on Ethiopian National Drug Formulary and Ethiopian National Standard Treatment Guideline, which are used in the hospital. Data was collected from January 18 to January 25, 2010 using appropriate data collection format. Results: Twenty six (65%) patients were in the age group of 15 to 49 years and twenty (50%) were females. Thirty eight (95%) and each of thirty seven (92.5%) cases were consistent with the Ethiopian National Standard Treatment Guideline & drug formulary regarding indication, dose & frequency of ciprofloxacin use in the outpatient department of Boru Meda hospital. 47.5% ciprofloxacin use has problem in duration of treatment . There were potential drug interactions with the drug in 40% of the cases. 10% of ciprofloxacin use was against contraindication. Conclusions: Due From the retrospective Drug Use Evaluation (DUE) study, it was identified that there was inappropriate ciprofloxacin use in the outpatient department of Boru Meda hospital even though the drug’s use regarding indications was a better performance and dosing practices were almost appropriate as per the criteria used for the study (assuming that there were no dose adjustments). There was a great problem concerning the duration of ciprofloxacin drug therapy. Ciprofloxacin use along with potentially interacting drugs and against contraindications was also another problem indicated in the study.