<em>Background:</em> Antisense peptide nucleic acids (PNAs) exhibit growth inhibitory effects on bacteria by inhibiting the expression of essential genes and could be promising therapeutic agents for treat...<em>Background:</em> Antisense peptide nucleic acids (PNAs) exhibit growth inhibitory effects on bacteria by inhibiting the expression of essential genes and could be promising therapeutic agents for treating bacterial infections. A study was carried out to determine the efficacy of several antisense PNAs in inhibiting extracellular and intracellular growth of <em>Mycobacterium smegmatis</em>. <em>Methods: </em>Six PNAs obtained from a commercial supplier were tested to evaluate the inhibitory effect on bacterial growth by inhibiting the expression of the following essential genes: <em>inhA </em>(a fatty acid elongase), <em>rpsL</em> (ribosomal S12 protein), <em>gyrA</em> (DNA gyrase), <em>pncA</em> (pyrazinamidase), <em>polA</em> (DNA polymerase I) and <em>rpoC</em> (RNA polymerase <em>β</em> subunit) of <em>M. smegmatis</em>. Each PNA was tested at 20 μM, 10 μM, 5 μM and 2.5 μM concentrations to determine whether they caused a dose dependent killing of <em>M. smegmatis</em> cultured in Middlebrook 7H9 broth or in a J774A.1 murine macrophage cell line.<em> Results:</em> In Middlebrook broth, the strong growth inhibitory effect against <em>M. smegmatis</em> was observed by PNAs targeting the <em>inhA </em>and <em>rpsL</em> genes at all four concentrations. The PNAs targeting the<em> pncA</em>, <em>polA</em> and<em> rpoC</em> genes were found to exhibit strong growth inhibition against <em>M. smegmatis</em> but only at 20 μM concentration. No growth inhibition of <em>M. smegmatis </em>was seen in pure culture when treated with PNAs targeting gyrA and a mismatch PNA targeting dnaG (DNA primase). All six PNAs showed killing of <em>M. smegmatis </em>in J774A.1 macrophage cell line that were statistically significant (p < 0.05). <em>Conclusion:</em> It may be concluded from this study that PNAs could be potential therapeutics for mycobacterial infections.展开更多
文摘<em>Background:</em> Antisense peptide nucleic acids (PNAs) exhibit growth inhibitory effects on bacteria by inhibiting the expression of essential genes and could be promising therapeutic agents for treating bacterial infections. A study was carried out to determine the efficacy of several antisense PNAs in inhibiting extracellular and intracellular growth of <em>Mycobacterium smegmatis</em>. <em>Methods: </em>Six PNAs obtained from a commercial supplier were tested to evaluate the inhibitory effect on bacterial growth by inhibiting the expression of the following essential genes: <em>inhA </em>(a fatty acid elongase), <em>rpsL</em> (ribosomal S12 protein), <em>gyrA</em> (DNA gyrase), <em>pncA</em> (pyrazinamidase), <em>polA</em> (DNA polymerase I) and <em>rpoC</em> (RNA polymerase <em>β</em> subunit) of <em>M. smegmatis</em>. Each PNA was tested at 20 μM, 10 μM, 5 μM and 2.5 μM concentrations to determine whether they caused a dose dependent killing of <em>M. smegmatis</em> cultured in Middlebrook 7H9 broth or in a J774A.1 murine macrophage cell line.<em> Results:</em> In Middlebrook broth, the strong growth inhibitory effect against <em>M. smegmatis</em> was observed by PNAs targeting the <em>inhA </em>and <em>rpsL</em> genes at all four concentrations. The PNAs targeting the<em> pncA</em>, <em>polA</em> and<em> rpoC</em> genes were found to exhibit strong growth inhibition against <em>M. smegmatis</em> but only at 20 μM concentration. No growth inhibition of <em>M. smegmatis </em>was seen in pure culture when treated with PNAs targeting gyrA and a mismatch PNA targeting dnaG (DNA primase). All six PNAs showed killing of <em>M. smegmatis </em>in J774A.1 macrophage cell line that were statistically significant (p < 0.05). <em>Conclusion:</em> It may be concluded from this study that PNAs could be potential therapeutics for mycobacterial infections.
