Abstract
The spread of multidrug-resistant (MDR) strains of bacteria necessitates the discovery of new classes of antibacterials and compounds that inhibit these resistance mechanisms. At present, there are no single chemical entity plant-derived antibacterials used clinically, and this chemically diverse group deserves consideration as a source for two major reasons. First, plants have exceptional ability to produce cytotoxic agents and second there is an ecological rationale that antimicrobial natural products should be present or synthesised de novo in plants following microbial attack to protect the producer from pathogenic microbes in its environment. We have been characterising plant-derived products that are either antibacterial in their own right, or modulators of resistance in bacterial strains possessing multidrug efflux mechanisms. These efflux transporters are responsible for resistance to certain antibiotics and antiseptics and occur in strains of methicillin-resistant Staphylococcus aureus (MRSA), a major clinical problem at present. We are also investigating plant sources for compounds with activity against mycobacteria with a view to discovering drug leads with potential activity toward tuberculosis (TB) producing species. This paper will briefly review the literature on plant derived bacterial resistance modifying agents and antibacterials. Examples in this area from our own work will be given. The activities of plant-derived antibacterials show that there are many potential new classes of antibacterial agents which should undergo further cytotoxicity, microbial specificity and preclinical studies.
Similar content being viewed by others
References
A Ahmad KA Khan VU Ahmad S Qazi (1986) ArticleTitleAntibacterial activity of juliflorine isolated from Prosopis juliflora Planta Med 4 285–288 Occurrence Handle3763718
S Anderson EE Glover KD Vaughan (1976) ArticleTitleThe N-Amination and subsequent oxidation by bromine of Imidazo[1,5-a] pyridines J. Chem. Soc. Perk. Trans 1 1722–1724 Occurrence Handle10.1039/p19760001722
G Appendino F Bianchi A Minassi O Sterner M Ballero S Gibbons (2002) ArticleTitleOligomeric Acylphloroglucinols from Myrtle (Myrtus communis) J. Nat. Prod 65 334–338 Occurrence Handle10.1021/np010441b Occurrence Handle11908974
JE Barnes LA Anderson JD Phillipson (2002) Herbal Medicine: A Guide for Health Care Professionals EditionNumber2 Pharmaceutical Press London
F Bucar T Kartnig (1995) ArticleTitleFlavone glucuronides of Lycopus virginicus Planta Med 61 378–380
A Chakraborty C Saha G Podder BK Chowdhury P Bhattacharyya (1995) ArticleTitleCarbazole alkaloid with antimicrobial activity from Clausena heptaphylla Phytochemistry 38 787–789 Occurrence Handle10.1016/0031-9422(94)00666-H Occurrence Handle7766168
M Chatterji S Unniraman S Mahadevan V Nagaraja (2001) ArticleTitleEffect of different classes of inhibitors on DNA gyrase from Mycobacterium smegmatis J. Antimicrob. Chemother 48 479–485 Occurrence Handle10.1093/jac/48.4.479 Occurrence Handle11581225
A Chevallier (2001) Encyclopedia of Medicinal Plants Dorling Kindersley Limited London
M Ciofalo S Petruso D Schillaci (1996) ArticleTitleQuantitative assay of photoinduced antibiotic activities of naturally-occurring 2,2′:5′,2”-terthiophenes Planta Med 62 374–375 Occurrence Handle8792675
NS Crowcroft M Catchpole (2002) ArticleTitleMortality from methicillin resistant Staphylococcus aureus in England and Wales: analysis of death certificates Brit. Med. J 325 1390–1391 Occurrence Handle12480853
S Gibbons EE Udo (2000) ArticleTitleThe effect of reserpine, a modulator of multidrug efflux pumps, on the in-vitro activity of tetracycline against clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) possessing the tet(K) determinant Phytother. Res 14 139–140 Occurrence Handle10.1002/(SICI)1099-1573(200003)14:2<139::AID-PTR608>3.0.CO;2-8 Occurrence Handle10685116
S Gibbons M Oluwatuyi GW Kaatz (2003a) ArticleTitleA Novel Inhibitor of Multidrug Efflux Pumps in Staphylococcus aureus. J. Antimicrob. Chemother 51 13–17 Occurrence Handle10.1093/jac/dkg044
S Gibbons NC Oluwatuyi M Veitch AI Gray (2003b) ArticleTitleBacterial Resistance Modifying Agents from Lycopus europaeus Phytochemistry 62 83–87 Occurrence Handle10.1016/S0031-9422(02)00446-6
S Gibbons (2004) ArticleTitleAnti-Staphylococcal Plant Natural Products Nat. Prod. Rep 21 263–277 Occurrence Handle10.1039/b212695h Occurrence Handle15042149
SH Gillespie I Morrissey D Everett (2001) ArticleTitleA comparison of the bactericidal activity of quinolone antibiotics in a Mycobacterium fortuitum model J. Med. Microbiol 50 565–570 Occurrence Handle11393294
NR Guz FR Stermitz (2000) ArticleTitleSynthesis and structures of regioisomeric hydnocarpin-type flavonolignans J. Nat. Prod 63 1140–1145 Occurrence Handle10.1021/np000166d Occurrence Handle10978213
JM Hamilton-Miller S Shah (1999) ArticleTitleDisorganization of cell division of methicillin-resistant Staphylococcus aureus by a component of tea (Camellia sinensis): a study by electron microscopy FEMS Microbiol. Lett 176 463–469 Occurrence Handle10.1016/S0378-1097(99)00273-6 Occurrence Handle10427729
JM Hamilton-Miller S Shah (2000) ArticleTitleActivity of the tea component epicatechin gallate and analogues against methicillin-resistant Staphylococcus aureus J. Antimicrob. Chemother 46 852–853 Occurrence Handle10.1093/jac/46.5.852 Occurrence Handle11062217
PC Hsieh SA Siegel B Rogers D Davis K Lewis (1998) ArticleTitleBacteria lacking a multidrug pump: a sensitive tool for drug discovery Proc. Natl. Acad. Sci. USA 95 6602–6606 Occurrence Handle10.1073/pnas.95.12.6602 Occurrence Handle9618458
AT Hübner (2003) ArticleTitleTreatment with Hypericum perforatum L. does not trigger decreased resistance in Staphylococcus aureus against antibiotics and hyperforin Phytomedicine 10 206–208 Occurrence Handle10.1078/094471103321659951 Occurrence Handle12725578
AA Hussein B Rodriguez (2000) ArticleTitleIsopimarane diterpenoids from Lycopus europaeus J. Nat. Prod 63 419–421 Occurrence Handle10.1021/np990519c Occurrence Handle10757737
M Iinuma H Tosa T Tanaka F Asai Y Kobayashi R Shimano K Miyauchi (1996) ArticleTitleAntibacterial activity of xanthones from guttiferaeous plants against methicillin-resistant Staphylococcus aureus J. Pharm. Pharmacol 48 861–865 Occurrence Handle8887739
D Jeremic S Macura S Milosavljevic V Vajs (1985) ArticleTitleA novel pimara-8(9),15-diene from Lycopus europaeus Tetrahedron 41 357–364 Occurrence Handle10.1016/S0040-4020(01)96427-0
Jevons MP (1961) Brit. Med. J., 1961, i, 124
E Kamory GM Keseru B Papp (1995) ArticleTitleIsolation and antibacterial activity of marchantin A, a cyclic bis(bibenzyl) constituent of Hungarian Marchantia polymorpha Planta Med 61 387–388 Occurrence Handle7480194
K Kawazoe Y Tsubouchi N Abdullah Y Takaish H Shibata T Higuti H Hori M Ogawa (2003) ArticleTitleSesquiterpenoids from Artemisia gilvescens and an anti-MRSA compound J. Nat. Prod 66 538–539 Occurrence Handle10.1021/np020593m Occurrence Handle12713410
D Lechner M Stavri M Oluwatuyi R Pereda-Miranda S Gibbons (2004) ArticleTitleThe anti-staphylococcal activity of Angelica dahurica (Bai Zhi) Phytochemistry 64 331–335 Occurrence Handle10.1016/j.phytochem.2003.11.010
PN Markham E Westhaus K Klyachko ME Johnson AA Neyfakh (1999) ArticleTitleMultiple novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus Antimicrob. Agents Chemother 43 2404–2408 Occurrence Handle10508015
NJ Marshall LJV Piddock (1997) ArticleTitleAntibacterial efflux systems Microbiologia 13 285–300 Occurrence Handle9353747
C Morel FR Stermitz G Tegos K Lewis (2003) ArticleTitleIsoflavones as potentiators of antibacterial activity J. Agric. Food Chem 51 5677–5679 Occurrence Handle10.1021/jf0302714 Occurrence Handle12952418
I Muhammad KA El Sayed JS Mossa MS Al-Said FS El-Feraly AM Clark CD Hufford S Oh AMS Mayer (2000) ArticleTitleBioactive 12-oleanene triterpene and secotriterpene acids from Maytenus undata J. Nat. Prod 63 605–610 Occurrence Handle10.1021/np990456y Occurrence Handle10843569
NP Nanayakkara CL Burandt SuffixJr. MR Jacob (2002) ArticleTitleFlavonoids with activity against methicillin-resistant Staphylococcus aureus from Dalea scandens var. paucifolia Planta Med 68 519–522 Occurrence Handle10.1055/s-2002-32554 Occurrence Handle12094295
K Nicolson G Evans PW O’Toole (1999) ArticleTitlePotentiation of methicillin activity against methicillin-resistant Staphylococcus aureus by diterpenes FEMS Microbiol. Lett 179 233–239 Occurrence Handle10.1016/S0378-1097(99)00417-6 Occurrence Handle10518721
M Oluwatuyi G Kaatz S Gibbons (2004) ArticleTitleAntibacterial and Resistance Modifying Activity of Rosmarinus officinalis Phytochemistry 65 3249–3254 Occurrence Handle10.1016/j.phytochem.2004.10.009 Occurrence Handle15561190
J Orjala P Mian T Rali O Sticher (1998) ArticleTitleGibbilimbols A-D, cytotoxic and antibacterial alkenylphenols from Piper gibbilimbum J. Nat. Prod 61 939–941 Occurrence Handle10.1021/np970529i Occurrence Handle9677279
TM Perl (1999) ArticleTitleThe threat of vancomycin resistance Am. J. Med 106 IssueID5A 26S–37S Occurrence Handle10.1016/S0002-9343(98)00354-4 Occurrence Handle10348061
R Philips (1977) Wild flowers of Britain Pan books Ltd London
J Reichling A Weseler R Saller (2001) ArticleTitleA current review of the antimicrobial activity of Hypericum perforatum L Pharmacopsychiatry 34 IssueIDSuppl 1 S116–118 Occurrence Handle10.1055/s-2001-15514 Occurrence Handle11518059
Resistance to Antibiotics (1998) Science and Technology – 7th Report to the House of Lords Committee, The Stationary Office, London
Rouhi AM (2003) Rediscovering Natural Products. Chem. Eng. News., 81: 77, 93 and 104
CM Schempp K Pelz A Wittmer E Schopf JC Simon (1999) ArticleTitleAntibacterial activity of hyperforin from St John’s wort, against multiresistant Staphylococcus aureus and gram-positive bacteria Lancet 353 2129 Occurrence Handle10.1016/S0140-6736(99)00214-7
A Schinkovitz S Gibbons M Stavri MJ Cocksedge F Bucar (2003) ArticleTitleOstruthin: An antimycobacterial coumarin from the roots of Peucedanum ostruthium Koch Planta Med 69 369–371 Occurrence Handle10.1055/s-2003-38876 Occurrence Handle12709907
FJ Schmitz AC Fluit M Luckefahr B Engler B Hofmann J Verhoef HP Heinz U Hadding ME Jones (1998) ArticleTitleThe effect of reserpine, an inhibitor of multidrug efflux pumps, on the in-vitro activities of ciprofloxacin, sparfloxacin and moxifloxacin against clinical isolates of Staphylococcus aureus J. Antimicrob. Chemother 42 807–810 Occurrence Handle10.1093/jac/42.6.807 Occurrence Handle10052906
WN Setzer MC Setzer RB Bates P Nakkiew BR Jackes L Chen MB McFerrin EJ Meehan (1999) ArticleTitleAntibacterial hydroxycinnamic esters from Piper caninum from Paluma, north Queensland, Australia. The crystal and molecular structure of (+)-bornyl coumarate Planta Med 65 747–749 Occurrence Handle10630119
S Shiota M Shimizu T Mizusima H Ito T Hatano T Yoshida T Tsuchiya (2000) ArticleTitleRestoration of effectiveness of beta-lactams on methicillin-resistant Staphylococcus aureus by tellimagrandin I from rose red FEMS Microbiol. Lett 185 135–138 Occurrence Handle10.1016/S0378-1097(00)00086-0 Occurrence Handle10754237
A Stapleton (2003) ArticleTitleNovel approaches to prevention of urinary tract infections Infect. Dis. Clin. North Am 17 457–471 Occurrence Handle10.1016/S0891-5520(03)00010-2 Occurrence Handle12848479
M Stavri KT Mathew F Bucar S Gibbons (2003) ArticleTitlePangelin, an Antimycobacterial Coumarin from Ducrosia anethifolia Planta Med 69 956–959 Occurrence Handle10.1055/s-2003-45109 Occurrence Handle14648403
FR Stermitz P Lorenz JN Tawara LA Zenewicz K Lewis (2000) ArticleTitleSynergy in a medicinal plant: antimicrobial action of berberine potentiated by 5′-methoxyhydnocarpin, a multidrug pump inhibitor Proc. Natl. Acad. Sci. USA 97 1433–1437 Occurrence Handle10.1073/pnas.030540597 Occurrence Handle10677479
FR Stermitz LN Scriven G Tegos K Lewis (2002) ArticleTitleTwo flavonols from Artemisa annua which potentiate the activity of berberine and norfloxacin against a resistant strain of Staphylococcus aureus Planta Med 68 1140–1141 Occurrence Handle10.1055/s-2002-36347 Occurrence Handle12494348
FR Stermitz KK Cashman KM Halligan C Morel GP Tegos K Lewis (2003) ArticleTitlePolyacylated neohesperidosides from Geranium caespitosum: bacterial multidrug resistance pump inhibitors Bioorg. Med. Chem. Lett 13 1915–1918 Occurrence Handle10.1016/S0960-894X(03)00316-0 Occurrence Handle12749897
G Tegos FR Stermitz O Lomovskaya K Lewis (2002) ArticleTitleMultidrug pump inhibitors uncover remarkable activity of plant antimicrobials Antimicrob. Agents Chemother 46 3133–3141 Occurrence Handle10.1128/AAC.46.10.3133-3141.2002 Occurrence Handle12234835
The National Audit Office – Report by the Comptroller and Auditor General. (17th of February, 2000), 6-121, The Stationary Office, London
S Trifunovic V Vajs S Macura N Juranic Z Djarmati R Jankov S Milosavljevic (1998) ArticleTitleOxidation products of hyperforin from Hypericum perforatum Phytochemistry 49 1305–1310 Occurrence Handle9842729
SM Tsao MC Yin (2001) ArticleTitleIn-vitro antimicrobial activity of four diallyl sulphides occurring naturally in garlic and Chinese leek oils J. Med. Microbiol 50 646–649 Occurrence Handle11444776
S Tsiodras HS Gold G Sakoulas GM Eliopoulos C Wennersten L Venkataraman RC Moellering MJ Ferraro (2001) ArticleTitleLinezolid resistance in a clinical isolate of Staphylococcus aureus Lancet 358 207 Occurrence Handle10.1016/S0140-6736(01)05410-1 Occurrence Handle11476839
V Vajs S Vugdelija S Trifunovic I Karadzic N Juranic S. Macura S Milosavljevic (2003) ArticleTitleFurther degradation product of hyperforin from Hypericum perforatum (St John’s Wort) Fitoterapia 74 439–444 Occurrence Handle12837358
Wagner H (1999) Arzneidrogen und ihre Inhaltsstoffe. Pharmazeutische Biologie Band 2. Wissenschaftliche Verlagsgesellschaft
GM Woldemichael G Wachter MP Singh WM Maiese BN Timmermann (2003) ArticleTitleAntibacterial diterpenes from Calceolaria pinifolia J. Nat. Prod 66 242–246 Occurrence Handle10.1021/np020380x Occurrence Handle12608857
TS Yam JM Hamilton-Miller S Shah (1998) ArticleTitleThe effect of a component of tea (Camellia sinensis) on methicillin resistance, PBP2′ synthesis, and beta-lactamase production in Staphylococcus aureus J. Antimicrob. Chemother 42 211–216 Occurrence Handle10.1093/jac/42.2.211 Occurrence Handle9738838
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gibbons, S. Plants as a Source of Bacterial Resistance Modulators and Anti-Infective Agents. Phytochem Rev 4, 63–78 (2005). https://doi.org/10.1007/s11101-005-2494-9
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11101-005-2494-9