Bacterial resistance to conventional antibiotics is a serious health problem. Unfortunately, only a few truly new antibiotics have been discovered during the last half century. Therefore, there is a need for new strategies. Liam's laboratory works in the general area of RNA biology and has pioneered the idea of using “antisense agents” as antibacterials. Whereas conventional antibiotics typically inhibit protein targets, antisense agents target “sense” messenger RNAs. As potential drugs, antisense agents can inhibit a wider range of target genes and act with improved species selective effects. This should enable pathogen targeting without damage to the normal flora. We are working with medicinal chemists to improve cell uptake and distribution properties.

In a related study, we observed that silencing bacterial growth essential genes at the RNA level sensitises bacteria to protein level inhibitors. This synergistic effect is being extended in the laboratory to develop sensitises whole-cell assays to detect new antibacterial compounds. For example, we are screening for new new antibacterials in extracts from plants and other natural sources, where they may be present at only low concentrations.

Finally, our laboratory has developed a novel nanoparticle-based-system for delivery of nucleic acids into cells, often called "transfection".  The technology is applicabel to a wide range of cell types, with potential in vivo applications..

Kamaruzzaman NF, Chong SQY, Edmondson-Brown KM, Ntow-Boahene W, Bardiau M, Good L.
Bactericidal and Anti-biofilm Effects of Polyhexamethylene Biguanide in Models of Intracellular and Biofilm of Staphylococcus aureus Isolated from Bovine Mastitis.  Front Microbiol. 2017 Aug 11;8:1518.

Nakhuda A, Josse AR, Gburcik V, Crossland H, Raymond F, Metairon S, Good L, Atherton PJ, Phillips SM, Timmons JA. 
Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss. Am J Clin Nutr. 2016 Aug 3. pii: ajcn132563

Chindera K, Mahato M, Sharma AK, Horsley H, Kloc-Muniak K, Kamaruzzaman NF, Kumar S, McFarlane A, Stach J, Bentin T, Good L. The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes. Sci Rep. 2016 Mar 21;6:23121. doi: 10.1038/srep23121

Kamaruzzaman, NF, Firdessa, R., Good, L. (2016)  Bactericidal effects of Polyhexamethylene Biguanide against intracellular Staphylococcus aureus EMRSA-15 and USA 300, Journal of Antimicrobial Chemotherapy, Jan 28. pii: dkv474

Chukwudi CU, Good L. Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action. J Antibiot (Tokyo). 2016 Jan 20. doi: 10.1038/ja.2015.145.

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 Microbiology, 15:262  .

Firdessa, R., Good, L., Amstalden, M. C., Chindera, K., Kamaruzzaman, N. F., Schultheis, M., Röger, B.,  Hecht, n., Oelschlaeger, t.a., Meinel, l. Lühmann, T.,  Moll, H. (2015). Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB). PLoS Negl Trop Dis, 9(10), e0004041. Retrieved from http://dx.doi.org/10.1371%2Fjournal.pntd.0004041

Holloway P, Musallam I, Whiting M, Good L, Van Winden, S, Silva-Fletcher, A, Ababneh, M, Abu-Basha, E, Guitian, J. (2015) Building capacity to reduce biological threats in the Middle East. Veterinary Record 2015;177:337-338 doi:10.1136/vr.h5136

Goh, S, Hohmeier, A, Stone, TC, Offord, V, Sarabia, F, Good, L (2015) Silencing of essential genes within a highly coordinated operon in Escherichia coli, Appl Environ Microbiol. 2015 Aug 15;81(16):5650-9. doi: 10.1128/AEM.01444-15

Chukwudi CU, Good L. (2015) The role of the hok/sok locus in bacterial response to stressful growth conditions. Microb Pathog. Feb;79:70-9.

Ghafourian S, Good L, Sekawi Z, Hamat RA, Soheili S, Sadeghifard N, Neela V. The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii. Mem Inst Oswaldo Cruz. (2014) Jul 3;109(4):502-5

Dixit, SK, Yadav, N, Kumar, S, Good, L and Awasthi, SK (2014) Synthesis and Antibacterial Activity of Novel  Fluroquinolone Analogs. Medicinal Chemistry Research.

Mondhe M, Chessher A, Goh S, Good L, Stach JE (2014) Species-Selective Killing of Bacteria by Antimicrobial Peptide-PNAs. PLoS One. (2014) Feb 18;9(2):e89082

Goh S, Stach J, Good L. Antisense Effects of PNAs in Bacteria. Methods Mol Biol. 2014;1050:223-36.

Uguru GC, Mondhe M, Goh S, Hesketh A, Bibb MJ, Good L, Stach JE (2013) Synthetic RNA Silencing of Actinorhodin Biosynthesis in Streptomyces coelicolor A3(2). PLoS One. Jun 27;8(6):e67509.

Goltermann L, Good L, Bentin T. (2013) Chaperonins fight aminoglycoside induced protein misfolding and promote short-term tolerance in Escherichia coli. Journal of Biological Chemistry.Link to paper

Johns, I, Verheyen, K., Good, L. & Rycroft, A. (2012)  Antimicrobial resistance in faecal Escherichia coli isolates from horses treated with antimicrobials: a longitudinal study in hospitalised and non-hospitalised horses, Vet. Microbiology 

Boberek, JM, Goh, S, Stach J & Good L. (2012) FtsZ as an antibacterial target. CABI 

Good, L., Goh, S and Stach, J. (2012) Antisense in Bacteria. Methods in Molecular Biology 

Stach, J.E.M & Good, L. (2011) Synthetic RNA silencing in bacteria - antimicrobial discovery and resistance breaking. Front. Microbio. 2:185. doi: 10.3389/fmicb.2011.00185 Link to paper

Attar L, Scott S, Goh S & Good L. (2011) A pestivirus DNA vaccine based on a non-antibiotic resistance Escherichia coli essential gene marker. Vaccine Link to paper

Arefian E, Kiani J, Soleimani M, Shariati SA, Aghaee-Bakhtiari SH, Atashi A, Gheisari Y, Ahmadbeigi N, Banaei-Moghaddam AM, Naderi M, Namvarasl N, Good L, Faridani OR (2011)  Analysis of microRNA signatures using size-coded ligation-mediated PCR.. Nucleic Acids Res. 2011 Apr 12.. Link to paper

Nakashima, N., Goh, S., Good, L. Tamura, N. (2011) Multiple-gene silencing using antisense RNAs in Escherichia coli. Methods in Molecular Biology

BOBEREK, JM, STACH J, GOOD L. (2010) Genetic evidence for inhibition of bacterial division protein FtsZ by berberine. PLoS One. 2010 Oct 29;5(10):e13745. Link to paper

BANSAL, S, TAWAR, U, SINGH. M, NIKKRAVESH, A, GOOD, L TANDON, V.( 2010) Old class but new dimethoxy analogue of benzimidazole: a bacterial topoisomerase I inhibitor. International Journal of Antimicrobial Agents 35;186-90. PubMed ID 20006473

BERGQUIST, H, NIKRAVESH, A, FERNNDEZ, RD, LARSSON, V, NGUYEN, C-H, GOOD, L, ZAIN, R. (2009) Structure-specific recognition of Friedreichs ataxia (GAA)n repeats by benzoquinoquinoxaline derivatives. ChemBiochem, 10(16):2629-37. PubMed ID 19746387

GOH, S., BOBEREK, J. M., NAKASHIMA, N., STACH, J., AND GOOD, L. (2009) Concurrent growth rate and transcript analyses reveal essential gene stringency in Escherichia coli, PLoS ONE 4, e6061. PubMed ID 19557168

GOH, S. AND GOOD. (2008) Plasmid selection in Escherichia coli using an endogenous essential gene marker. BMC Biotechnology, 11;8:61. PubMed ID 18694482

FARIDANI, OF, MCINERNEY, GM, GRADIN, K AND GOOD, L. (2008) Specific ligation to double-stranded RNA for analysis of cellular RNA::RNA interactions. Nucleic Acids Research, 36(16):e99. PubMed ID 18628292

JUNKES, C., WESSOLOWSKI, A., FARNAUD, S., EVANS, R. W., GOOD, L., BIENERT, M. & DATHE, M. (2008) The interaction of arginine- and tryptophan-rich cyclic hexapeptides with Escherichia coli membranes. J Pept Sci 14, 535-543. PubMed ID 17985396

SCHEELE, C., PETROVIC, N., FAGHIHI, M. A., LASSMANN, T., FREDRIKSSON, K., ROOYACKERS, O., WAHLESTEDT, C., GOOD, L. & TIMMONS, J. A. (2007) The human PINK1 locus is regulated in vivo by a non-coding natural antisense RNA during modulation of mitochondrial function. BMC Genomics 8, 74. PubMed ID 17362513

NIKRAVESH, A., DRYSELIUS, R., FARIDANI, O. R., GOH, S., SADEGHIZADEH, M., BEHMANESH, M., GANYU, A., KLOK, E. J., ZAIN, R. & GOOD, L. (2007) Antisense PNA accumulates in Escherichia coli and mediates a long post-antibiotic effect. Mol Ther 15, 1537-1542. PubMed ID 17534267

TIMMONS, J. A. & GOOD, L. (2006) Does everything now make (anti)sense? Biochem Soc Trans 34, 1148-1150. PubMed ID 17073772

NAKASHIMA, N., TAMURA, T. & GOOD, L. (2006) Paired termini stabilize antisense RNAs and enhance conditional gene silencing in Escherichia coli. Nucleic Acids Res 34, e138. PubMed ID 17062631

LUNDIN, K. E., GOOD, L., STROMBERG, R., GRASLUND, A. & SMITH, C. I. (2006) Biological activity and biotechnological aspects of peptide nucleic acid. Adv Genet 56, 1-51. PubMed ID 16735154

FARIDANI, O. R., NIKRAVESH, A., PANDEY, D. P., GERDES, K. & GOOD, L. (2006) Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli. Nucleic Acids Res 34, 5915-5922. PubMed ID 17065468

DRYSELIUS, R., NIKRAVESH, A., KULYTE, A., GOH, S. & GOOD, L. (2006) Variable coordination of cotranscribed genes in Escherichia coli following antisense repression. BMC Microbiol 6, 97. PubMed ID 17118182

PARENTEAU, J., KLINCK, R., GOOD, L., LANGEL, U., WELLINGER, R. J. & ELELA, S. A. (2005) Free uptake of cell-penetrating peptides by fission yeast. FEBS Lett 579, 4873-4878. PubMed ID 16111683

KULYTE, A., NEKHOTIAEVA, N., AWASTHI, S. K. & GOOD, L. (2005) Inhibition of Mycobacterium smegmatis gene expression and growth using antisense peptide nucleic acids. J Mol Microbiol Biotechnol 9, 101-109. PubMed ID 16319499

KULYTE, A., DRYSELIUS, R., KARLSSON, J. & GOOD, L. (2005) Gene selective suppression of nonsense termination using antisense agents. Biochim Biophys Acta 1730, 165-172. PubMed ID 16135388

DRYSELIUS, R., NEKHOTIAEVA, N. & GOOD, L. (2005) Antimicrobial synergy between mRNA- and protein-level inhibitors. J Antimicrob Chemother 56, 97-103. PubMed ID 15914490

AMIRI, H., NEKHOTIAEVA, N., SUN, J. S., NGUYEN, C. H., GRIERSON, D. S., GOOD, L. & ZAIN, R. (2005) Benzoquinoquinoxaline derivatives stabilize and cleave H-DNA and repress transcription downstream of a triplex-forming sequence. J Mol Biol 351, 776-783. PubMed ID 16045927

NEKHOTIAEVA, N., ELMQUIST, A., RAJARAO, G. K., HALLBRINK, M., LANGEL, U. & GOOD, L. (2004) Cell entry and antimicrobial properties of eukaryotic cell-penetrating peptides. FASEB J 18, 394-396. PubMed ID 14656995

NEKHOTIAEVA, N., AWASTHI, S. K., NIELSEN, P. E. & GOOD, L. (2004) Inhibition of Staphylococcus aureus gene expression and growth using antisense peptide nucleic acids. Mol Ther 10, 652-659. PubMed ID 15451449

TAWAR, U., JAIN, A. K., CHANDRA, R., SINGH, Y., DWARAKANATH, B. S., CHAUDHURY, N. K., GOOD, L. & TANDON, V. (2003) Minor groove binding DNA ligands with expanded A/T sequence length recognition, selective binding to bent DNA regions and enhanced fluorescent properties. Biochemistry 42, 13339-13346. PubMed ID 14609344

RAJARAO, G. K., NEKHOTIAEVA, N. & GOOD, L. (2003) The signal peptide NPFSD fused to ricin A chain enhances cell uptake and cytotoxicity in Candida albicans. Biochem Biophys Res Commun 301, 529-534. PubMed ID 12565894

GOOD, L. (2003) Translation repression by antisense sequences. Cell Mol Life Sci 60, 854-861. PubMed ID 12827275

GOOD, L. (2003) Diverse antisense mechanisms and applications. Cell Mol Life Sci 60, 823-824. PubMed ID 12827271

DRYSELIUS, R., NEKHOTIAEVA, N., NIELSEN, P. E. & GOOD, L. (2003) Antibiotic-free bacterial strain selection using antisense peptide nucleic acid. Biotechniques 35, 1060-1064. PubMed ID 14628680

DRYSELIUS, R., ASWASTI, S. K., RAJARAO, G. K., NIELSEN, P. E. & GOOD, L. (2003) The translation start codon region is sensitive to antisense PNA inhibition in Escherichia coli. Oligonucleotides 13, 427-433. PubMed ID 15025910

TREMBLAY, A., LAMONTAGNE, B., CATALA, M., YAM, Y., LAROSE, S., GOOD, L. & ELELA, S. A. (2002) A physical interaction between Gar1p and Rnt1pi is required for the nuclear import of H/ACA small nucleolar RNA-associated proteins. Mol Cell Biol 22, 4792-4802. PubMed ID 12052886

RAJARAO, G. K., NEKHOTIAEVA, N. & GOOD, L. (2002) Peptide-mediated delivery of green fluorescent protein into yeasts and bacteria. FEMS Microbiol Lett 215, 267-272. PubMed ID 12399045

GOOD, L. (2002) Antisense inhibition of bacterial gene expression and cell growth. Methods Mol Biol 208, 237-248. PubMed ID 12229292

ERIKSSON, M., NIELSEN, P. E. & GOOD, L. (2002) Cell permeabilization and uptake of antisense peptide-peptide nucleic acid (PNA) into Escherichia coli. J Biol Chem 277, 7144-7147. PubMed ID 11739379

GOOD, L., AWASTHI, S. K., DRYSELIUS, R., LARSSON, O. & NIELSEN, P. E. (2001) Bactericidal antisense effects of peptide-PNA conjugates. Nat Biotechnol 19, 360-364. PubMed ID 11283595

WAHLESTEDT, C., SALMI, P., GOOD, L., KELA, J., JOHNSSON, T., HOKFELT, T., BROBERGER, C., PORRECA, F., LAI, J., REN, K., OSSIPOV, M., KOSHKIN, A., JAKOBSEN, N., SKOUV, J., OERUM, H., JACOBSEN, M. H. & WENGEL, J. (2000) Potent and nontoxic antisense oligonucleotides containing locked nucleic acids. Proc Natl Acad Sci U S A 97, 5633-5638. PubMed ID 10805816

GOOD, L., SANDBERG, R., LARSSON, O., NIELSEN, P. E. & WAHLESTEDT, C. (2000) Antisense PNA effects in Escherichia coli are limited by the outer-membrane LPS layer. Microbiology 146 ( Pt 10), 2665-2670. PubMed ID 11021941

INTINE, R. V., GOOD, L. & NAZAR, R. N. (1999) Essential structural features in the Schizosaccharomyces pombe pre-rRNA 5' external transcribed spacer. J Mol Biol 286, 695-708. PubMed ID 10024444

GOOD, L. & NIELSEN, P. E. (1999) Peptide nucleic acid (PNA) antisense effects in Escherichia coli. Curr Issues Mol Biol 1, 111-116. PubMed ID 11475695

GOOD, L. & NIELSEN, P. E. (1998) Antisense inhibition of gene expression in bacteria by PNA targeted to mRNA. Nat Biotechnol 16, 355-358. PubMed ID 9555726

GOOD, L. & NIELSEN, P. E. (1998) Inhibition of translation and bacterial growth by peptide nucleic acid targeted to ribosomal RNA. Proc Natl Acad Sci U S A 95, 2073-2076. PubMed ID 9482840

GOOD, L. & NIELSEN, P. E. (1997) Progress in developing PNA as a gene-targeted drug. Antisense Nucleic Acid Drug Dev 7, 431-437. PubMed ID 9303195

GOOD, L. & NAZAR, R. N. (1997) Plasmid mini-preparations from culture streaks. Biotechniques 22, 404-406. PubMed ID 9067008

GOOD, L., INTINE, R. V. & NAZAR, R. N. (1997) The ribosomal-RNA-processing pathway in Schizosaccharomyces pombe. Eur J Biochem 247, 314-321. PubMed ID 9249042

GOOD, L. & NAZAR, R. N. (1995) Visualization of CsCl/EtdBr plasmid preparations under visible light. Biotechniques 18, 556-558. PubMed ID 7598879

ABOU ELELA, S., GOOD, L. & NAZAR, R. N. (1995) An efficiently expressed 5.8S rRNA 'tag' for in vivo studies of yeast rRNA biosynthesis and function. Biochim Biophys Acta 1262, 164-167. PubMed ID 7599193

MELEKHOVETS, Y. F., GOOD, L., ELELA, S. A. & NAZAR, R. N. (1994) Intragenic processing in yeast rRNA is dependent on the 3' external transcribed spacer. J Mol Biol 239, 170-180. PubMed ID 8196052

GOOD, L., ELELA, S. A. & NAZAR, R. N. (1994) Tetrahymena ribozyme disrupts rRNA processing in yeast. J Biol Chem 269, 22169-22172. PubMed ID 8071340

ABOU ELELA, S., GOOD, L., MELEKHOVETS, Y. F. & NAZAR, R. N. (1994) Inhibition of protein synthesis by an efficiently expressed mutation in the yeast 5.8S ribosomal RNA. Nucleic Acids Res 22, 686-693. PubMed ID 8127718

GOOD, L. & NAZAR, R. N. (1992) An improved thermal cycle for two-step PCR-based targeted mutagenesis. Nucleic Acids Res 20, 4934. PubMed ID 1408812

His interests centre around genetics and general microbiology, which he teaches to the 2nd and 3rd year BVetMed undergraduates. He also supervises graduate PhD students with theses in his field.

He has a long-term interest in developing and improving antimicrobial strategies.

• Action project on Alternatives to Veterinary Antimicrobials (AVANT)

  

  Professor of Veterinary Bacteriology Luca Guardabassi is the coordinator of a large EU Innovation Action project on Alternatives to Veterinary Antimicrobials (AVANT) involving 8 industries, 5 universities and the Federation of Veterinarians of Europe.

  AVANT is a multi-actor inter-sectorial project aimed at developing alternatives to antimicrobials for the management of bacterial infections in pigs, especially diarrhoea during the weaning period, as the major indication for antimicrobial use in livestock in Europe. 

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• Novel nanotechnology for research, bioprocessing and antimicrobial therapy in human and animal health (Tecrea)

  

  The RVC has developed a novel nanoparticle-based-system for delivery of nucleic acids into cells, often called "transfection".  The technology is applicable to a wide range of cell types, with potential in vivo applications.

  Following patent filings and company creation to commercialise the technology, impacts include investment from private individuals and venture capital; sales of research kits and services; influence on regulatory agencies’ decisions and guidance, and out-licensing for both human and veterinary product applications. In addition to three (two completed) clinical trials in human health, the technology platform has been developed via a multi-million dollar (USD) license deal to a global animal health business for both production and companion animal applications.

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