Insight into DNA Gyrase inhibition using quantitative structure-Activity relationships and structure-based drug design approaches

The emergence of certain bacterial strains resistant to antibiotics has become a major public health problem, hence the need to develop new antibiotic molecules. Bacterial DNA gyrase, a type II DNA topoisomerase found in all bacteria is a proven target for antibacterial chemotherapy. Our objective is designing novel DNA Gyrase inhibitors using Quantitative StructureActivity Relationships and Structure-Based Drug Design Approaches. We used bioinformatics tools, biological databases like PDB (Protein DataBank), Binding Databases and software's like, MarvinView, MarvinSketch, PyMOL, AutoDockTools-1.5.6. The 3D crystal structure of DNA Gyrase was extracted from PDB (code: 4DHU) and we characterized the active site. Using 83 compounds with different Ki were extracted from Binding Databases, we built and validated a QSAR Model (PLS regression) and we confirmed the interesting correlation between predicted and experimental Ki (R2=0,843). Four molecules were chosen to be docked into DNA Gyrase active site using AutoDockTools. The compound which has the low Ki (Benzimidazole urea analogue 5) shows more binding affinity with score value of ΔG= -8,6 kcal/mol than the others compounds. So, it would be very interesting to synthesis this promising compound and to test in vitro its antibacterial properties.

Mobile phones of hospital workers: a potential reservoir for the transmission of pathogenic bacteria

Background: Mobile phones are increasingly associated with the transmission of pathogenic microbial agents. In the clinical setting where there is usually high exposure to pathogens, these devices may serve as vehicles for the transmission/spread of pathogens. This study determined the prevalence of bacterial contamination of mobile phones of health workers and the predisposing factors, in order to ascertain the risk of transmission of pathogenic bacteria through mobile phones. Methodology: This study was carried out in a private medical center at Mbouda, Cameroon, involving 78 health workers including health professionals (nurses, physicians, laboratory scientists) and hospital support workers (cleaners, cashiers and security guards), recruited by convenient sampling. Sterile swab sticks moistened with physiological saline were used to swab about three quarter of the surface of each phone. The swabs were cultured on MacConkey and Mannitol Salt agar plates which were incubated aerobically at 37oC for 24 hours, while Chocolate agar plate was incubated in a candle extinction jar for microaerophilic condition. The isolates were identified using standard biochemical tests including catalase, coagulase, and the analytical profile index (API) system. Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 20.0. Results: Mobile phones of 75 of the 78 (96.2%) health workers were contaminated, with highest contamination rates for the phones of laboratory scientists (100%, 12/12), followed by support staff (98.9%, 13/14), nurses (97.7%, 43/44) and physicians (87.3%, 7/8), but the difference in contamination rates was not statistically significant (p=0.349). A total of 112 bacteria belonging to 12 genera were isolated, with predominance of Staphylococcus aureus (31.3%, n=35), Micrococcus spp (30.4%, n=34), coagulase negative staphylococci (10.7%, n=12) and Pseudomonas spp (5.4%, n=6). The laboratory (18.8%, 21/112) and medical wards (16.1%, 18/112) had the highest bacterial contamination of mobile phones (p=0.041), and more bacterial species were isolated from smartphones (68.8%, n=77/112) than keypad phones (31.2%, n=35/112) (p=0.032). There was no significant difference between phone contamination rates and the practice of hand hygiene or decontamination of work surfaces (p>0.05). Conclusion: The presence of potentially pathogenic bacteria on cell phones of health-care workers emphasizes the role of fomites in the transmission of infectious diseases. Consequently, good hand hygiene and decontamination practices are encouraged among health workers in order to limit the spread of hospital-acquired infections.

Organisms associated with bacterial vaginosis in Nigerian women as determined by PCR-DGGE and 16S rRNA Gene Sequence

Background: Bacterial vaginosis (BV) is a condition with diverse etiology.This condition predisposes women to increased susceptibility to sexually transmitted diseases; including human immunodeficiency virus (HIV) infections and preterm birth. The diagnostic methods currently adopted in the evaluation of patient samples for BV are arguably Amsel criteria; and Nugent score that require microscopy and expert interpretation.These two methods are still subjective. Objective: The objective of this study was to determine the organisms present in the vagina of 34 HIV negative Nigerian women diagnosed as having bacterial vaginosis by using molecular techniques. Methods:The vaginal samples were subjected to DNA extraction; and amplified with eubacterial primers via PCR.The PCR products were separated using denaturing gradient gel electrophoresis (DGGE). Bands were excised; re-amplified; purified and sequenced. Sequence identification was performed using the BLAST algorithm and Genbank data base. Results: Mycoplasma hominis (12/34; 35) was the most common isolate and 9 (26) contained one of two clones of an unusual Rainbow Trout intestinal bacterium; while unculturable Streptococcus sp; and other bacteria made up the remaining isolates. Con-clusions:The findings indicate further diversity in the etiological agents associated with BV; and raise the question as to whether diagnosis and management of this condition needs to be re-evaluated in countries like Nigeria.There is some controversy over the clinical importance of BV; as it was once regarded as a disease caused by Gardnerella and presenting as an odourous discharge condition; but is now diagnosed without necessarily the presence of these organisms or signs. With the incidence of BV aligned to an increased risk of HIV in a country ravaged by this virus; the effective eradication of BV can only be achieved if appropriate therapies are delivered