Taming wall teichoic acid multi drug resistance in gram positive pathogens


ABSTRACT:

Wall teichoic acid (WTA) plays important roles in cell growth, division, morphology and as a virulence factor. TagG and TagH are involved in the translocation of the teichoic acids on to the membrane surface. Present study was aimed to evaluate the effect of drugs at their half of MIC on tagG and tagH mRNA expressions through semi quantitative reverse transcription-polymerase chain reaction (RT-PCR). In the current investigation, twenty six methicillin-resistant Staphylococcus aureus (MRSA) were used to identify the occurrence of tagG and tagH genes using the previously reported primers. Susceptibility study in the selected isolates for drugs was carried out with broth dilution method according to the Clinical and Laboratory Standards Institute guidelines. To explore the effect of drugs on expression of tagG and tagH, TagG and TagH positive MRSA strains cultures were treated with different drugs, Vancoplus, ceftriaxone, vancomycin, linezolid, teicoplanin and daptomycin, at half of MIC for 24 h. Our results revealed that all the isolates were found to be TagG and TagH positive. Susceptibility results revealed that Vancoplus was found to be more susceptible against these isolates with MIC values 0.25 to 4 µg/ml. Second most active agent was linezolid with MIC values 1 to 32 µg/ml. The remaining drugs were resistant to these strains with MICs of ceftriaxone, teicoplanin, vancomycin, daptomycin, were in the ranges of 256 to 512 µg/ml. Vancoplus showed respectively 79.2±8.3 and 85.6±8.6% down-regulation in tagG and tagH genes down-regulation when treated with its half of MIC whereas linezolid produced 68.3±7.2 and 73.2±7.9% down-regulation in tagG and tagH genes, respectively. The other comparator drugs produced only 30 to 45 % down-regulation in both of the genes. From the above results, it can be seen that Vancoplus not only found to be more active against these isolates but also significantly down-regulate the expression of tagG and tagH genes which are actively involved in the translocation of teichoic acid and thus can be helpful tool in taming MDR gram positive resistance due to WTA.  

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For more details to visit @ http://www.jocpr.com/articles/taming-wall-teichoic-acid-multi-drug-resistance-in-gram-positive-pathogens.pdf


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