Quorum sensing (QS) system in Pseudomonas aeruginosa may be an important target for pharmacological intervention. The present study aimed to investigate the synergetic activity of sub-MIC concentrations of curcumin (C) with ceftazidime (CAZ) and ciprofloxacin (CIP) against P. aeroginusa QS system. We determined the MIC and synergistic activity of C, CAZ and CIP against P. aeroginusa PAO1 using broth microdilution and checkerboard titration methods. The activity of sub-MIC (1/4 and 1/16 MIC) concentrations of C on the QS signal molecules was assessed using a reporter strain assay. The influence of sub-MIC of C, CAZ and CIP alone and in combination on motility and biofilm formation was also determined and confirmed by RT-PCR to test the expression of QS regulatory genes lasI, lasR, rhlI and rhlR. The addition of C decreased the MIC of CAZ and CIP. Curcumin showed synergistic effects with CAZ and additive activity with CIP. Treated PAO1 cultures in the presence of C showed significant reduction of signals C12-HSL and C4-HSL (P < 0.05). Sub-MIC concentrations (1/4 and 1/16 MIC) of C, CAZ and CIP alone and in combination significantly reduced swarming and twitching motilities and biofilm formation. Expression of QS regulatory genes lasI, lasR, rhlI, and rhlR using 1/4 MIC of C, CAZ and CIP alone and in combination was repressed significantly relative to untreated PAO1. Our results indicate that a combination of the sub-MIC concentration of C and CAZ exhibited synergism against P. aeroginusa QS system. This combination could lead to the development of a new combined therapy against P. aeruginosa.
Bacterial meningitis is one of the most severe infectious diseases with high rate of morbidity and mortality in developing countries. The current study aimed to investigate the frequency of etiological agents of bacterial meningitis among patients admitted to three hospitals in Zanjan, Iran. A total of 100 cerebrospinal fluid (CSF) samples were collected aseptically, and cytochemical analysis, Gram staining, culture, and PCR were performed. Forty-six percent of CSF samples had positive bacterial culture results. However, PCR showed a higher detection rate of bacterial meningitis causing pathogens when compared with culture (52% vs. 46%; p > 0.05). Fifty-two percent of patients with bacterial meningitis were aged <1 year. The most prevalent pathogen was
Streptococcus pneumoniae
(36.5%), followed by
Neisseria meningitidis
(28.8%) and
Streptococcus agalactiae
(15.4%).
Listeria monocytogenes
was not isolated from CSF culture. The frequency of
Haemophilus influenzae, L. monocytogenes
and
Escherichia coli
was 7.7%, 1.9% and 9.6%, respectively. Although in patients aged <1 year,
S. pneumonia, N. meningitidis
and group B streptococcus were the most common pathogens causing meningitis, and in patients aged between 1 and 10 years,
Escherichia coli
was the most common. According to the results, the culture was less effective for diagnosis of bacterial meningitis than PCR. Our findings indicate that the most common causative agents of bacterial meningitis in Iran may be vaccine-preventable pathogens. Therefore, the prevention and control measures should be considered to reduce the incidence of bacterial meningitis.
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