Abstract
Antisense therapeutics are a biotechnological form of antibiotic therapy using chemical analogues of short single-stranded nucleic acid sequences modified to form stable oligomers. These molecules are termed antisense oligonucleotides (ASOs) because their sequence is complementary, via Watson-Crick specific base pairing, to their target messenger RNA (mRNA). ASOs modify gene expression in this sequence-dependent manner by binding to its complementary mRNA and inhibiting its translation into protein through steric blockage and/or through RNase degradation of the ASO/RNA duplex. The widespread use of conventional antibiotics has led to the increasing emergence of multiple drug-resistant pathogenic bacteria. There is an urgent need to develop alternative therapeutic strategies to reduce the morbidity and mortality associated with bacterial infections, and until recently, the use of ASOs as therapeutic agents has been essentially limited to eukaryotic cells, with ASOs as antibacterials having been largely unexplored primarily due to the poor uptake efficiency of antisense molecules by bacteria. There are conceptual advantages to bacterial antisense antibiotic therapies, including a sequence-dependent approach that allows for a rational design to multiple specific molecular targets. This review summarizes the current knowledge of antisense bacterial biotechnology and highlights the recent progress and the current obstacles in their development for therapeutic applications.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abushahba MFN, Mohammad H, Thangamani S, Hussein AAA, Seleem MN (2016) Impact of different cell penetrating peptides on the efficacy of antisense therapeutics for targeting intracellular pathogens. Sci Rep 6(1):20832. https://doi.org/10.1038/srep20832
Ahmed M (2017) Peptides, polypeptides and peptide-polymer hybrids as nucleic acid carriers. Biomater Sci 5(2017):2188–2211. https://doi.org/10.1039/c7bm00584a
Ayhan DH, Tamer YT, Akbar M, Bailey SM, Wong M, Daly SM, Greenberg DE, Toprak E (2016) Sequence-specific targeting of bacterial resistance genes increases antibiotic efficacy. PLoS Biol 14(9):e1002552. https://doi.org/10.1371/journal.pbio.1002552
Bai H, Zhou Y, Hou Z, Xue X, Meng J, Luo X (2011) Targeting bacterial RNA polymerase: promises for future antisense antibiotics development. Infect Disord Drug Targets 11(2):175–187. https://doi.org/10.2174/187152611795589708
Bai H, Sang G, You Y, Xue X, Zhou Y, Hou Z, Meng J, Luo X (2012) Targeting RNA polymerase primary σ 70 as a therapeutic strategy against methicillin-resistant Staphylococcus aureus by antisense peptide nucleic acid. PLoS One 7(1):e29886. https://doi.org/10.1371/journal.pone.0029886
Beaman GM, Dennison SR, Phoenix DA (2014) Antimicrobial therapy based on antisense agents. In: Novel antimicrobial agents and strategies. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp 357–386
Bo X, Wang S (2005) TargetFinder: a software for antisense oligonucleotide target site selection based on MAST and secondary structures of target mRNA. Bioinformatics 21(8):1401–1402. https://doi.org/10.1093/bioinformatics/bti211
Boisguérin P, Deshayes S, Gait MJ, O’Donovan L, Godfrey C, Betts CA, Wood MJA, Lebleu B (2015) Delivery of therapeutic oligonucleotides with cell penetrating peptides. Adv Drug Deliv Rev 87:52–67. https://doi.org/10.1016/j.addr.2015.02.008
Castro-Roa D, Zenkin N (2015) Methodology for the analysis of transcription and translation in transcription-coupled-to-translation systems in vitro. Methods 86:51–59. https://doi.org/10.1016/j.ymeth.2015.05.029
Chen Z, Hu Y, Meng J, Li M, Hou Z, Zhou Y, Luo X, Xue X (2015) Efficient transfection of phosphorothioate oligodeoxyribonucleotides by lipofectamine 2000 into different bacteria. Curr Drug Deliv 12:1–8
Choung S, Kim YJ, Kim S, Park H-O, Choi Y-C (2006) Chemical modification of siRNAs to improve serum stability without loss of efficacy. Biochem Biophys Res Commun 342(3):919–927. https://doi.org/10.1016/j.bbrc.2006.02.049
Clatworthy AE, Pierson E, Hung DT (2007) Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol 3(9):541–548. https://doi.org/10.1038/nchembio.2007.24
Crooke ST (2017) Molecular mechanisms of antisense oligonucleotides. Nucleic Acid Ther 27(2):70–77. https://doi.org/10.1089/nat.2016.0656
Da F, Yao L, Su Z, Hou Z, Li Z, Xue X, Meng J, Luo X (2017) Antisense locked nucleic acids targeting agrA inhibit quorum sensing and pathogenesis of community-associated methicillin-resistant Staphylococcus aureus. J Appl Microbiol 122(1):257–267. https://doi.org/10.1111/jam.13321
Daly SM, Sturge CR, Felder-Scott CF, Geller BL, Greenberg DE (2017) MCR-1 inhibition with peptide-conjugated Phosphorodiamidate morpholino oligomers restores sensitivity to polymyxin in Escherichia coli. MBio 8(6)
Davies-Sala C, Soler-Bistué A, Bonomo RA, Zorreguieta A, Tolmasky ME (2015) External guide sequence technology: a path to development of novel antimicrobial therapeutics. Ann N Y Acad Sci 1354(1):98–110. https://doi.org/10.1111/nyas.12755
Dias N, Stein CA (2002) Antisense oligonucleotides: basic concepts and mechanisms. Mol Cancer Ther 1(5):347–355
Dinan AM, Loftus BJ (2013) (Non-)translational medicine: targeting bacterial RNA. Front Genet 4:230. https://doi.org/10.3389/fgene.2013.00230
Dong H, Zhang Z, Tang X, Huang S, Li H, Peng B, Dong C (2016) Structural insights into cardiolipin transfer from the inner membrane to the outer membrane by PbgA in Gram-negative bacteria. Sci Rep 6(1):30815. https://doi.org/10.1038/srep30815
Dowdy SF (2017) Overcoming cellular barriers for RNA therapeutics. Nat Biotechnol 35(3):222–229. https://doi.org/10.1038/nbt.3802
Doyle DF, Braasch DA, Simmons CG, Janowski BA, Corey DR (2001) Inhibition of gene expression inside cells by peptide nucleic acids: effect of mRNA target sequence, mismatched bases, and PNA length. Biochemistry 40(1):53–64. https://doi.org/10.1021/bi0020630
Dryselius R, Nekhotiaeva N, Good L (2005) Antimicrobial synergy between mRNA- and protein-level inhibitors. J Antimicrob Chemother 56(1):97–103. https://doi.org/10.1093/jac/dki173
Eckstein F (2014) Phosphorothioates, essential components of therapeutic oligonucleotides. Nucleic Acid Ther 24(6):374–387. https://doi.org/10.1089/nat.2014.0506
Geary RS, Norris D, Yu R, Bennett CF (2015) Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides. Adv Drug Deliv Rev 87:46–51. https://doi.org/10.1016/j.addr.2015.01.008
Geller BL, Deere JD, Stein DA, Kroeker AD, Moulton HM, Iversen PL (2003) Inhibition of gene expression in Escherichia coli by antisense phosphorodiamidate morpholino oligomers. Antimicrob Agents Chemother 47(10):3233–3239. https://doi.org/10.1128/AAC.47.10.3233-3239.2003
Geller BL, Marshall-Batty K, Schnell FJ, McKnight MM, Iversen PL, Greenberg DE (2013) Gene-silencing antisense oligomers inhibit acinetobacter growth in vitro and in vivo. J Infect Dis 208(10):1553–1560. https://doi.org/10.1093/infdis/jit460
Ghosal A, Nielsen PE (2012) Potent antibacterial antisense peptide-peptide nucleic acid conjugates against Pseudomonas aeruginosa. Nucleic Acid Ther 22(5):323–334. https://doi.org/10.1089/nat.2012.0370
Goh S, Stach J, Good L (2014) Antisense effects of PNAs in bacteria. In: Methods in molecular biology. Clifton, N.J, pp 223–236
Goh S, Loeffler A, Lloyd DH, Nair SP, Good L (2015) Oxacillin sensitization of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius by antisense peptide nucleic acids in vitro. BMC Microbiol 15(1):262. https://doi.org/10.1186/s12866-015-0599-x
Good L, Nielsen PE (1998) Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA. Nat Biotechnol 16(4):355–358. https://doi.org/10.1038/nbt0498-355
Good L, Sandberg R, Larsson O, Nielsen PE, Wahlestedt C (2000) Antisense PNA effects in Escherichia coli are limited by the outer-membrane LPS layer. Microbiology 146(10):2665–2670. https://doi.org/10.1099/00221287-146-10-2665
Greenberg DE, Marshall-Batty KR, Brinster LR, Zarember KA, Shaw PA, Mellbye BL, Iversen PL, Holland SM, Geller BL (2010) Antisense phosphorodiamidate morpholino oligomers targeted to an essential gene inhibit Burkholderia cepacia complex. J Infect Dis 201(12):1822–1830. https://doi.org/10.1086/652807
Hagedorn PH, Hansen BR, Koch T, Lindow M (2017) Managing the sequence-specificity of antisense oligonucleotides in drug discovery. Nucleic Acids Res 45(5):2262–2282. https://doi.org/10.1093/nar/gkx056
Hamada M, Ono Y, Kiryu H, Sato K, Kato Y, Fukunaga T, Mori R, Asai K (2016) Rtools: a web server for various secondary structural analyses on single RNA sequences. Nucleic Acids Res 44(W1):W302–W307. https://doi.org/10.1093/nar/gkw337
Hansen AM, Bonke G, Larsen CJ, Yavari N, Nielsen PE, Franzyk H (2016) Antibacterial peptide nucleic acid—antimicrobial peptide (PNA-AMP) conjugates: antisense targeting of fatty acid biosynthesis. Bioconjug Chem 27(4):863–867. https://doi.org/10.1021/acs.bioconjchem.6b00013
Harth G, Zamecnik PC, Tang JY, Tabatadze D, Horwitz MA (2000) Treatment of Mycobacterium tuberculosis with antisense oligonucleotides to glutamine synthetase mRNA inhibits glutamine synthetase activity, formation of the poly-L-glutamate/glutamine cell wall structure, and bacterial replication. Proc Natl Acad Sci U S A 97(1):418–423. https://doi.org/10.1073/pnas.97.1.418
Harth G, Zamecnik PC, Tabatadze D, Pierson K, Horwitz MA (2007) Hairpin extensions enhance the efficacy of mycolyl transferase-specific antisense oligonucleotides targeting Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 104(17):7199–7204. https://doi.org/10.1073/pnas.0701725104
Hatamoto M, Ohashi A, Imachi H (2010) Peptide nucleic acids (PNAs) antisense effect to bacterial growth and their application potentiality in biotechnology. Appl Microbiol Biotechnol 86(2):397–402. https://doi.org/10.1007/s00253-009-2387-8
Hegarty JP, Krzeminski J, Sharma AK, Guzman-Villanueva D, Weissig V, Stewart DB (2016) Bolaamphiphile-based nanocomplex delivery of phosphorothioate gapmer antisense oligonucleotides as a treatment for Clostridium difficile. Int J Nanomedicine 11:3607–3619. https://doi.org/10.2147/IJN.S109600
Howard JJ, Sturge CR, Moustafa DA, Daly SM, Marshall-Batty KR, Felder CF, Zamora D, Yabe-Gill M, Labandeira-Rey M, Bailey SM, Wong M, Goldberg JB, Geller BL, Greenberg DE (2017) Inhibition of Pseudomonas aeruginosa by peptide-conjugated phosphorodiamidate morpholino oligomers. Antimicrob Agents Chemother 61(4):e01938–e01916. https://doi.org/10.1128/AAC.01938-16
Hu J, Xia Y, Xiong Y, Li X, Su X (2011) Inhibition of biofilm formation by the antisense peptide nucleic acids targeted at the motA gene in Pseudomonas aeruginosa PAO1 strain. World J Microbiol Biotechnol 27(9):1981–1987. https://doi.org/10.1007/s11274-011-0658-x
Jackson A, Jani S, Davies-Sala C, Soler-Bistué AJC, Zorreguieta A, Tolmasky ME (2016) Assessment of configurations and chemistries of bridged nucleic acids-containing oligomers as external guide sequences: a methodology for inhibition of expression of antibiotic resistance genes. Biol Methods Protoc 1:bpw001
Järver P, Coursindel T, EL Andaloussi S, Godfrey C, Wood MJ, Gait MJ (2012) Peptide-mediated cell and in vivo delivery of antisense oligonucleotides and siRNA. Mol Ther Nucleic Acids 1:e27. https://doi.org/10.1038/mtna.2012.18
Ji Y, Lei T (2013) Antisense RNA regulation and application in the development of novel antibiotics to combat multidrug resistant bacteria. Sci Prog 96(1):43–60. https://doi.org/10.3184/003685013X13617194309028
Juliano RL (2016) The delivery of therapeutic oligonucleotides. Nucleic Acids Res 44(14):6518–6548. https://doi.org/10.1093/nar/gkw236
Kalesinskas P, Kačergius T, Ambrozaitis A, Jimbo R, Ericson D (2015) Streptococcus mutans biofilm inhibition using antisense oligonucleotide to glucosyltransferases B and C. Acta Medica Litu 22:85–92
Khvorova A, Watts JK (2017) The chemical evolution of oligonucleotide therapies of clinical utility. Nat Biotechnol 35(3):238–248. https://doi.org/10.1038/nbt.3765
Kulyté A, Nekhotiaeva N, Awasthi SK, Good L (2005) Inhibition of Mycobacterium smegmatis gene expression and growth using antisense peptide nucleic acids. J Mol Microbiol Biotechnol 9(2):101–109. https://doi.org/10.1159/000088840
Kurreck J, Wyszko E, Gillen C, Erdmann VA (2002) Design of antisense oligonucleotides stabilized by locked nucleic acids. Nucleic Acids Res 30(9):1911–1918. https://doi.org/10.1093/nar/30.9.1911
Kurupati P, Tan KSW, Kumarasinghe G, Poh CL (2007) Inhibition of gene expression and growth by antisense peptide nucleic acids in a multiresistant -lactamase-producing Klebsiella pneumoniae strain. Antimicrob Agents Chemother 51(3):805–811. https://doi.org/10.1128/AAC.00709-06
Lennox KA, Vakulskas CA, Behlke MA (2017) Non-nucleotide modification of anti-miRNA oligonucleotides. In: Methods in molecular biology. Clifton, N.J, pp 51–69
Lima WF, Monia BP, Ecker DJ, Freier SM (1992) Implication of RNA structure on antisense oligonucleotide hybridization kinetics. Biochemistry 31(48):12055–12061. https://doi.org/10.1021/bi00163a013
Lima WF, Vickers TA, Nichols J, Li C, Crooke ST (2014) Defining the factors that contribute to on-target specificity of antisense oligonucleotides. PLoS One 9(7):e101752. https://doi.org/10.1371/journal.pone.0101752
Lopez C, Arivett BA, Actis LA, Tolmasky ME (2015) Inhibition of AAC(6′)-Ib-mediated resistance to amikacin in Acinetobacter baumannii by an antisense peptide-conjugated 2′,4′-bridged nucleic acid-NC-DNA hybrid oligomer. Antimicrob Agents Chemother 59(9):5798–5803. https://doi.org/10.1128/AAC.01304-15
Mamusa M, Barbero F, Montis C, Cutillo L, Gonzalez-Paredes A, Berti D (2017a) Inclusion of oligonucleotide antimicrobials in biocompatible cationic liposomes: a structural study. J Colloid Interface Sci 508:476–487. https://doi.org/10.1016/j.jcis.2017.08.080
Mamusa M, Sitia L, Barbero F, Ruyra A, Calvo TD, Montis C, Gonzalez-Paredes A, Wheeler GN, Morris CJ, McArthur M, Berti D (2017b) Cationic liposomal vectors incorporating a bolaamphiphile for oligonucleotide antimicrobials. Biochim Biophys Acta Biomembr 1859(10):1767–1777. https://doi.org/10.1016/j.bbamem.2017.06.006
Marín-Menéndez A, Montis C, Díaz-Calvo T, Carta D, Hatzixanthis K, Morris CJ, McArthur M, Berti D (2017) Antimicrobial nanoplexes meet model bacterial membranes: the key role of Cardiolipin. Sci Rep 7:41242. https://doi.org/10.1038/srep41242
Mellbye BL, Puckett SE, Tilley LD, Iversen PL, Geller BL (2009) Variations in amino acid composition of antisense peptide-phosphorodiamidate morpholino oligomer affect potency against Escherichia coli in vitro and in vivo. Antimicrob Agents Chemother 53(2):525–530. https://doi.org/10.1128/AAC.00917-08
Mellbye BL, Weller DD, Hassinger JN, Reeves MD, Lovejoy CE, Iversen PL, Geller BL (2010) Cationic phosphorodiamidate morpholino oligomers efficiently prevent growth of Escherichia coli in vitro and in vivo. J Antimicrob Chemother 65(1):98–106. https://doi.org/10.1093/jac/dkp392
Meng J, Wang H, Hou Z, Chen T, Fu J, Ma X, He G, Xue X, Jia M, Luo X (2009) Novel anion liposome-encapsulated antisense oligonucleotide restores susceptibility of methicillin-resistant Staphylococcus aureus and rescues mice from lethal sepsis by targeting mecA. Antimicrob Agents Chemother 53(7):2871–2878. https://doi.org/10.1128/AAC.01542-08
Meng J, Da F, Ma X, Wang N, Wang Y, Zhang H, Li M, Zhou Y, Xue X, Hou Z, Jia M, Luo X (2015) Antisense growth inhibition of methicillin-resistant Staphylococcus aureus by locked nucleic acid conjugated with cell-penetrating peptide as a novel FtsZ inhibitor. Antimicrob Agents Chemother 59(2):914–922. https://doi.org/10.1128/AAC.03781-14
Mondhe M, Chessher A, Goh S, Good L, Stach JEM (2014) Species-selective killing of bacteria by antimicrobial peptide-PNAs. PLoS One 9(2):e89082. https://doi.org/10.1371/journal.pone.0089082
Monia BP, Lesnik EA, Gonzalez C, Lima WF, McGee D, Guinosso CJ, Kawasaki AM, Cook PD, Freier SM (1993) Evaluation of 2′-modified oligonucleotides containing 2′-deoxy gaps as antisense inhibitors of gene expression. J Biol Chem 268(19):14514–14522
Monia BP, Sasmor H, Johnston JF, Freier SM, Lesnik EA, Muller M, Geiger T, Altmann KH, Moser H, Fabbro D (1996) Sequence-specific antitumor activity of a phosphorothioate oligodeoxyribonucleotide targeted to human C-raf kinase supports an antisense mechanism of action in vivo. Proc Natl Acad Sci U S A 93(26):15481–15484. https://doi.org/10.1073/pnas.93.26.15481
Morris MC, Deshayes S, Heitz F, Divita G (2008) Cell-penetrating peptides: from molecular mechanisms to therapeutics. Biol Cell 100(4):201–217. https://doi.org/10.1042/BC20070116
Nekhotiaeva N, Awasthi SK, Nielsen PE, Good L (2004) Inhibition of Staphylococcus aureus gene expression and growth using antisense peptide nucleic acids. Mol Ther 10(4):652–659. https://doi.org/10.1016/j.ymthe.2004.07.006
Oh E, Zhang Q, Jeon B (2014) Target optimization for peptide nucleic acid (PNA)-mediated antisense inhibition of the CmeABC multidrug efflux pump in Campylobacter jejuni. J Antimicrob Chemother 69(2):375–380. https://doi.org/10.1093/jac/dkt381
Otsuka T, Brauer AL, Kirkham C, Sully EK, Pettigrew MM, Kong Y, Geller BL, Murphy TF (2017) Antimicrobial activity of antisense peptide-peptide nucleic acid conjugates against non-typeable Haemophilus influenzae in planktonic and biofilm forms. J Antimicrob Chemother 72(1):137–144. https://doi.org/10.1093/jac/dkw384
Patel RR, Sundin GW, Yang C-H, Wang J, Huntley RB, Yuan X, Zeng Q (2017) Exploration of using antisense peptide nucleic acid (PNA)-cell penetrating peptide (CPP) as a novel bactericide against fire blight pathogen Erwinia amylovora. Front Microbiol 8:687. https://doi.org/10.3389/fmicb.2017.00687
Patenge N, Pappesch R, Krawack F, Walda C, Mraheil MA, Jacob A, Hain T, Kreikemeyer B (2013) Inhibition of growth and gene expression by PNA-peptide conjugates in Streptococcus pyogenes. Mol Ther Nucleic Acids 2:e132. https://doi.org/10.1038/mtna.2013.62
Pieńko T, Wierzba AJ, Wojciechowska M, Gryko D, Trylska J (2017) Conformational dynamics of cyanocobalamin and its conjugates with peptide nucleic acids. J Phys Chem B 121(14):2968–2979. https://doi.org/10.1021/acs.jpcb.7b00649
Rajasekaran P, Alexander JC, Seleem MN, Jain N, Sriranganathan N, Wattam AR, Setubal JC, Boyle SM (2013) Peptide nucleic acids inhibit growth of Brucella suis in pure culture and in infected murine macrophages. Int J Antimicrob Agents 41(4):358–362. https://doi.org/10.1016/j.ijantimicag.2012.11.017
Rasmussen LCV, Sperling-Petersen HU, Mortensen KK (2007) Hitting bacteria at the heart of the central dogma: sequence-specific inhibition. Microb Cell Factories 6(1):24. https://doi.org/10.1186/1475-2859-6-24
Readman JB, Dickson G, Coldham NG (2016) Translational inhibition of CTX-M extended spectrum β-lactamase in clinical strains of Escherichia coli by synthetic antisense oligonucleotides partially restores sensitivity to cefotaxime. Front Microbiol 7:373. https://doi.org/10.3389/fmicb.2016.00373
Reissmann S (2014) Cell penetration: scope and limitations by the application of cell-penetrating peptides. J Pept Sci 20(10):760–784. https://doi.org/10.1002/psc.2672
Reuter JS, Mathews DH (2010) RNAstructure: software for RNA secondary structure prediction and analysis. BMC Bioinformatics 11(1):129. https://doi.org/10.1186/1471-2105-11-129
Równicki M, Wojciechowska M, Wierzba AJ, Czarnecki J, Bartosik D, Gryko D, Trylska J (2017) Vitamin B12 as a carrier of peptide nucleic acid (PNA) into bacterial cells. Sci Rep 7(1):7644. https://doi.org/10.1038/s41598-017-08032-8
Rutherford ST, Bassler BL (2012) Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med 2(11):a012427–a012427. https://doi.org/10.1101/cshperspect.a012427
Sawyer AJ, Wesolowski D, Gandotra N, Stojadinovic A, Izadjoo M, Altman S, Kyriakides TR (2013) A peptide-morpholino oligomer conjugate targeting Staphylococcus aureus gyrA mRNA improves healing in an infected mouse cutaneous wound model. Int J Pharm 453(2):651–655. https://doi.org/10.1016/j.ijpharm.2013.05.041
Shen N, Ko J, Xiao G, Wesolowski D, Shan G, Geller B, Izadjoo M, Altman S (2009) Inactivation of expression of several genes in a variety of bacterial species by EGS technology. Proc Natl Acad Sci U S A 106(20):8163–8168. https://doi.org/10.1073/pnas.0903491106
Shi N-Q, Qi X-R, Xiang B, Zhang Y (2014) A survey on “Trojan Horse” peptides: opportunities, issues and controlled entry to “Troy”. J Control Release 194:53–70. https://doi.org/10.1016/j.jconrel.2014.08.014
Shi J, Li X, Dong M, Graham M, Yadav N, Liang C (2017) JNSViewer—A JavaScript-based nucleotide sequence viewer for DNA/RNA secondary structures. PLoS One 12(6):e0179040. https://doi.org/10.1371/journal.pone.0179040
Stein CA, Castanotto D (2017) FDA-approved oligonucleotide therapies in 2017. Mol Ther 25(5):1069–1075. https://doi.org/10.1016/j.ymthe.2017.03.023
Sully EK, Geller BL (2016) Antisense antimicrobial therapeutics. Curr Opin Microbiol 33:47–55. https://doi.org/10.1016/j.mib.2016.05.017
Sully EK, Geller BL, Li L, Moody CM, Bailey SM, Moore AL, Wong M, Nordmann P, Daly SM, Sturge CR, Greenberg DE (2017) Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo. J Antimicrob Chemother 72(3):782–790. https://doi.org/10.1093/jac/dkw476
Tan X-X, Actor JK, Chen Y (2005) Peptide nucleic acid antisense oligomer as a therapeutic strategy against bacterial infection: proof of principle using mouse intraperitoneal infection. Antimicrob Agents Chemother 49(8):3203–3207. https://doi.org/10.1128/AAC.49.8.3203-3207.2005
Tilley LD, Hine OS, Kellogg JA, Hassinger JN, Weller DD, Iversen PL, Geller BL (2006) Gene-specific effects of antisense phosphorodiamidate morpholino oligomer-peptide conjugates on Escherichia coli and Salmonella enterica Serovar typhimurium in pure culture and in tissue culture. Antimicrob Agents Chemother 50(8):2789–2796. https://doi.org/10.1128/AAC.01286-05
Wahlestedt C, Nielsen PE, Larsson O, Sandberg R, Good L (2000) Antisense PNA effects in Escherichia coli are limited by the outer-membrane LPS layer. Microbiology 146:2665–2670
Wang H, Meng J, Jia M, Ma X, He G, Yu J, Wang R, Bai H, Hou Z, Luo X (2010) oprM as a new target for reversion of multidrug resistance in Pseudomonas aeruginosa by antisense phosphorothioate oligodeoxynucleotides. FEMS Immunol Med Microbiol 60(3):275–282. https://doi.org/10.1111/j.1574-695X.2010.00742.x
Weissig V, Lizano C, Torchilin VP (2000) Selective DNA release from DQAsome/DNA complexes at mitochondria-like membranes. Drug Deliv 7(1):1–5. https://doi.org/10.1080/107175400266722
Wesolowski D, Tae HS, Gandotra N, Llopis P, Shen N, Altman S (2011) Basic peptide-morpholino oligomer conjugate that is very effective in killing bacteria by gene-specific and nonspecific modes. Proc Natl Acad Sci 108(40):16582–16587. https://doi.org/10.1073/pnas.1112561108
Wu Y, Qu R, Huang Y, Shi B, Liu M, Li Y, ZJ L (2016) RNAex: an RNA secondary structure prediction server enhanced by high-throughput structure-probing data. Nucleic Acids Res 44(W1):W294–W301. https://doi.org/10.1093/nar/gkw362
Zamecnik PC, Stephenson ML (1978) Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc Natl Acad Sci U S A 75(1):280–284. https://doi.org/10.1073/pnas.75.1.280
Zhao Q-Q, Chen J-L, Lv T-F, He C-X, Tang G-P, Liang W-Q, Tabata Y, Gao J-Q (2009) N/P ratio significantly influences the transfection efficiency and cytotoxicity of a polyethylenimine/chitosan/DNA complex. Biol Pharm Bull 32(4):706–710. https://doi.org/10.1248/bpb.32.706
Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31(13):3406–3415. https://doi.org/10.1093/nar/gkg595
Funding
This work was supported by a grant from the National Institutes of Health, grant # R21AI132353 (Stewart- PI).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with animal or human participants performed by any of the authors.
Rights and permissions
About this article
Cite this article
Hegarty, J.P., Stewart, D.B. Advances in therapeutic bacterial antisense biotechnology. Appl Microbiol Biotechnol 102, 1055–1065 (2018). https://doi.org/10.1007/s00253-017-8671-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-017-8671-0