combating multidrug resistance bacteria with essential oils

COMBATING MULTIDRUG RESISTANT BACTERIA WITH ESSENTIAL OILSMiguel Diaz

MICROBIAL COMPETITION

http://www.livescience.com/

• Competition for limited resources• Excretion of chemicals that are

toxic and inhibit growth

http://virtuallaboratory.colorado.edu

COEVOLUTION• Intrinsic resistance• Spontaneous mutations

http://learn.genetics.utah.edu/

PATHOGENS• Disease causing organisms

www.cdc.gov

http://www.bacteriainphotos.com/bacteria-photo-gallery.html

BACTERIA• Bacterial

Classification• Gram Positive• Gram Negative

DISCOVERY OF ANTIBIOTICS• 1928 Alexander Fleming

discovered Penicillin• Antibiotics have had a

significant impact on human health and life

• “Wonder” drug

http://sciencenational.tumblr.com/

MODES OF ACTION• Selective for bacterial cells• Unique processes• Metabolic pathways

• Bacteriostatic vs Bactericidal• Narrow vs Broad Spectrum

ANTIBIOTICS• Treat bacterial infections• Life saving• extending the human lifespan

• Naturally, Synthetic, Semi-Synthetic• Zone of inhibition• Minimum Inhibition Concentration

(MIC)

ERA OF ANTIBIOTICS

• Overuse• Misuse

"The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism.”

A. Fleming

RESISTANCE• Intrinsic Evolutionary event• Genes chromosomal or plasmid

• HGT• R plasmids

https://www.niaid.nih.gov

R-PLASMIDS

https://classconnection.s3.amazonaws.com

• Plasmids• Non-chromosomal DNA• Housekeeping genes• Some carry resistant genes• R-plasmids

ANTIBIOTIC RESISTANCE

MECHANISM OF RESISTANCE• Modify and inactivate

• ẞ-lactams • Penicillin

• Prevent drug uptake• Chloramphenicol

• Pump it out• Efflux Pump

• Tetracycline

HORIZONTAL GENE TRANSFER• Sharing of genetic material

• across different genera• 3 mechanisms

• Transformation• uptake of DNA from

the environment• Transduction

• Virus mediated• Conjugation

• cell to cell sharing • type IV pili

MULTIDRUG RESISTANCE

http://www.moleculin.com/

Multidrug Efflux Pump

http://evolution.berkeley.edu/

• R-plasmid with many resistant genes

MULTIDRUG RESISTANCE• ESKAPE Pathogens• Enterococcus faecium (VRE)• Staphylococcus aureus (MRSA)• Klebsiella and Escherichia coli producing ESBL• Acinetobacter baumannii• Pseudomonas aeruginosa• Enterbacteriaceae

POST ANTIBIOTIC ERA?

• Little research and development• Mutations can happen quickly

and are easily shared• What now?

“ We are headed to a post antibiotic era, in which common infections and minor injuries can once again kill” WHO 2015

http://bk.asia-city.com

ESSENTIAL OILS

http://www.questnetproxy.com/

• Traditional medicine• Topical or inhaled• Some toxic if ingested

• Generally safe• Chemotype• Changes in chemical

phenotype• Steam distillation

ESSENTIAL OIL: MODES OF ACTION

http://www.mdpi.com/pharmaceuticals

• Degrade cell wall• Damage cytoplasmic membrane• Increase permeability• Leakage of cell contents• Damage membrane proteins• Coagulation of cytoplasm• Depletion of proton motor force

TERPENOIDS• Secondary plant metabolite• Isoprene subunits• Volatile Compounds• Easley evaporated• Give plants fragrance (essence)

MELALEUCA ALTERNIFOLIA

http://www.teamessence.com.my/

• Native to Australia• Aboriginals use it for treating

infections• Know for its antiseptic, antibiotic

properties• Main constituents

• terpinen-4-ol • -terpineol

TEA TREE OIL• Cell Membrane Permeability• Leak K+

• E. coli and S. aureus• Cell Respiration• Decrease O2 consumption rate

TEA TREE

Lee et al. 2014

MENTHA PIPERITA

https://www.tuinplant.nl

• Native to Europe and Middle East

• Menthol and Mentone• Medicinal Uses• Analgesic, cooling,

antiemetic• muscle rubs

Bakkali et al. 2008

PEPPERMINT OIL

Singh et al. (2011)

PEPPERMINT OIL

Bazargani and Rohloff (2016)• Anti-plasmid activity• Menthol 96%• In combo with promethazine 100%

Anti-biofilm

EUCALYPTUS CAMALDULENSIS

https://upload.wikimedia.org/wikipedia/commons/8/82/Eucalyptus_trunk_zebra_pattern.jpg

• Indigenous to Australia• Medicinal Purpose

• anesthetic, antiseptic, astringent• Constitutes

• p-cymene (35.0%)• cryptone (13.7%)• tanins (11%)• terpinen-4-ol (5.7%)

EUCALYPTUS

http://www.mdpi.com/molecules

Jazani et al. 2012

OTHER ESSENTIAL OILS

ESSENTIAL OILS AND MDRO• Essential oils can reduce the use of antibiotic

• Preventative measures• Reduce inflammation response• Antiseptic

• Cleaning hospital surfaces• Alternative treatments

• Effective against a broad spectrum of bacteria• Synergistic effects

• In combination with antibiotics• Decrease MIC• Increase zone inhibition

REFRENCES• Bazargani MM, Rohloff J. 2016. Antibiofilm activity of essential oils and plant extracts against

Staphylococcus aureus and Escherichia coli biofilms. Food Control 61:156–164.• www.cdc.gov• Cox.S.D. 2000. The model of antimicrobial action of the essential oil of Melaleuca alternifolia. J. Appl.

Microbiol. 88:170–175.• Jazani NH, Mikaili P, Shayegh J, Haghighi N, Aghamohammadi N, Zartoshti M. 2012. The hydro-

alcoholic extract of leaves of Eucalyptus camaldulensis Dehnh. has antibacterial activity on multi-drug resistant bacteria isolates. J. Appl. Biol. Sci. 6:37–40.

• Knezevic P, Aleksic V, Simin N, Svircev E, Petrovic A, Mimica-Dukic N. 2016. Antimicrobial activity of Eucalyptus camaldulensis essential oils and their interactions with conventional antimicrobial agents against multi-drug resistant Acinetobacter baumannii. J. Ethnopharmacol. 178:125–136.

• Lee RLP, Leung PHM, Wong TKS. 2014. A randomized controlled trial of topical tea tree preparation for MRSA colonized wounds. Int. J. Nurs. Sci. 1:7–14.

• Singh R, Shushni MAM, Belkheir A. 2015. Antibacterial and antioxidant activities of Mentha piperita L. Arab. J. Chem. 8:322–328.