Maneesh Paul-Satyaseela

In vitro profiling of antimethicillin-resistant Staphylococcus aureus activity of thymoquinone against selected type and clinical strains.

This study explores antimethicillin‐resistant Staphylococcus aureus (MRSA) activity of a bioactive phytochemical constituent, thymoquinone obtained from the medicinal herb, Nigella sativa Linn. Based on initial assessment on crude extract of seeds of Nigella sativa Linn, the pure active constituent was employed in the study. A total of 99 MRSA strains which comprised of 40 types and 59 clinical strains were selected for the study. Minimum inhibitory concentration (MIC), bactericidal activity, postantibiotic effect (PAE) and propensity to select resistant mutants were determined using standard protocols. Results revealed that thymoquinone exhibited MIC in the range of 8–16 μg ml−1 and MIC90 of 16 μg ml−1 against MRSA strains. It was bactericidal to MRSA by demonstrating >3 log kill. It showed a longer PAE of 3·2 ± 0·2 h. Upon exposure to high‐density inoculum of MRSA, it did not select resistant mutants. Transmission electron microscopy of thymoquinone‐treated MRSA showed no lysis but damage to cell wall and cell membrane which corroborated well with the salt tolerance and bacteriolysis assays. In conclusion, MIC90, bactericidal property, longer PAE, absence of resistant mutant selection and damages in cell membrane and cell wall imply a promising anti‐MRSA activity of thymoquinone.

Antibiotic susceptibility pattern of Enterobacteriaceae and non-fermenter Gram-negative clinical isolates of microbial resource orchid.

Background: Microbial resource orchid is a collection of Gram-positive and Gram-negative clinical isolates sourced from different hospitals and diagnostic laboratories in India. We determined the antibiotic susceptibility of a set of Gram-negative Enterobacteriaceae and non-fermenter clinical isolates from microbial resource orchid, collected during the period of 2002-2012 against commonly used antibiotics. Materials and Methods: A total of 247 Gram negative strains consisting of 142 Enterobacteriaceae and 105 non-fermenters from microbial resource orchid were selected for determining minimum inhibitory concentration against β-lactams, aminoglycosides, quinolone, and tetracycline by agar dilution method as per clinical and laboratory standards institute guidelines. Results: All the isolates had high resistance to ampicillin, piperacillin, ceftazidime, gentamicin, tetracycline, and ciprofloxacin. Pseudomonas aeruginosa showed moderate resistance to carbapenems. Conclusion: This study demonstrated the high level of antibiotic resistance among the strains collected under microbial resource orchid and further, such data and the strains can be used in new chemical entities profiling.

In vitro antibacterial activities of a novel oxazolidinone, OCID0050

OBJECTIVES In the pursuit of developing a second-generation oxazolidinone, we have identified OCID0050 as a novel oxazolidinone with enhanced activity against bacterial strains resistant to methicillin, vancomycin and linezolid. METHODS MIC and MBC determinations were performed according to CLSI guidelines. Linezolid-resistant bacterial strains were generated in-house; inoculum effect, pH effect and kill kinetics experiments were performed as per standard protocols. RESULTS AND CONCLUSIONS OCID0050 demonstrated better inhibitory potency against many of the tested clinically significant strains by generally showing 2-4-fold lower MICs than linezolid. In addition, it has higher inhibitory activity against linezolid-resistant strains.

Staphylococcus aureus: Overview of Bacteriology, Clinical Diseases, Epidemiology, Antibiotic Resistance and Therapeutic Approach

Staphylococcus aureus is an important human pathogen that causes wide range of infectious conditions both in nosocomial and community settings. The Gram-positive pathogen is armed with battery of virulence factors that facilitate to establish infections in the hosts. The organism is well known for its ability to acquire resistance to various antibiotic classes. The emergence and spread of methicillin-resistant S. aureus (MRSA) strains which are often multi-drug resistant in hospitals and subsequently in community resulted in significant mortality and morbidity. The epidemiology of MRSA has been evolving since its initial outbreak which necessitates a comprehensive medical approach to tackle this pathogen. Vancomycin has been the drug of choice for years but its utility was challenged by the emergence of resistance. In the last 10 years or so, newer anti-MRSA antibiotics were approved for clinical use. However, being notorious for developing antibiotic resistance, there is a continuous need for exploring novel anti-MRSA agents from various sources including plants and evaluation of non-antibiotic approaches.

Novel hydroxamates potentiated in vitro activity of fluconazole against Candida albicans

A set of 12 novel hydroxamate compounds (NHCs), structurally designed as inhibitors of histone deacetylase (HDAC) enzyme, were synthesized at our facility. These were adamantane derivatives with N-hydroxyacetamide as pharmacophore, and each of these compounds was tested for potentiating activity on fluconazole. The concentration of fluconazole which completely inhibited (concentration of complete inhibition [CCI]) the growth of Candida albicans ATCC 90028 and C. albicans ATCC 64550 was determined by micro-dilution method in the absence and presence of NHCs. The CCI of fluconazole without the NHC combination was 64 μg/ml and 1024 μg/ml against C. albicans ATCC 90028 and C. albicans ATCC 64550, respectively. The majority of the NHCs potentiated the fluconazole activity markedly as CCI of fluconazole against C. albicans ATCC 90028 reduced to 0.25 μg/ml. Similarly, CCI of fluconazole against C. albicans ATCC 64550 reduced to 4–8 μg/ml in combination with majority of NHCs while the best activity was displayed by the compound 1 with a reduction of CCI to 0.5 μg/ml. The study results revealed the potential usage of hydroxamate derivatives, structurally designed as HDAC inhibitors to enhance the activity of fluconazole against C. albicans.