Essential Gene(s) Targeted by Peptide Nucleic Acids Kills Mycobacterium smegmatis in Culture and in Infected Macrophages

dc.contributor.authorIslam, Md. Arifulen
dc.contributor.authorKhatun, Mst. Minaraen
dc.contributor.authorSriranganathan, Nammalwaren
dc.contributor.authorBoyle, Stephen M.en
dc.description.abstractBackground: 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 Mycobacterium smegmatis. Methods : 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: inhA (a fatty acid elongase), rpsL (ribosomal S12 protein), gyrA (DNA gyrase), pncA (pyrazinamidase), polA (DNA polymerase I) and rpoC (RNA polymerase β subunit) of M. smegmatis . 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 M. smegmatis cultured in Middlebrook 7H9 broth or in a J774A.1 murine macrophage cell line. Results : In Middlebrook broth, the strong growth inhibitory effect against M. smegmatis was observed by PNAs targeting the inhA and rpsL genes at all four concentrations. The PNAs targeting the pncA, polA and rpoC genes were found to exhibit strong growth inhibition against M. smegmatis but only at 20 μM concentration. No growth inhibition of M. smegmatis 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 M. smegmatis in J774A.1 macrophage cell line that were statistically significant (p < 0.05). Conclusion: It may be concluded from this study that PNAs could be potential therapeutics for mycobacterial infections.en
dc.description.sponsorshipThis research was funded through grants from NIH to SMB (5R03AI083735-02) and from The Islamic Development Bank to MAI.en
dc.description.versionPublished versionen
dc.format.extent9 pagesen
dc.identifier.citationIslam, M.A., Khatun, M.M., Sriranganathan, N. and Boyle, S.M. (2021) Essential Gene(s) Targeted by Peptide Nucleic Acids Kills Mycobacterium smegmatis in Culture and in Infected Macrophages. Advances in Infectious Diseases , 11, 156-164.
dc.publisherScientific Research Publishingen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.subjectMiddlebrook 7H9 Broth Cultureen
dc.subjectJ774A.1 Murine Macrophage Cell Lineen
dc.subjectAntisense Therapyen
dc.subjectPeptide Nucleic Aciden
dc.subjectCell Penetrating Peptideen
dc.titleEssential Gene(s) Targeted by Peptide Nucleic Acids Kills Mycobacterium smegmatis in Culture and in Infected Macrophagesen
dc.title.serialAdvances in Infectious Diseasesen
dc.typeArticle - Refereeden


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