Antibiotic resistance (AR) is a global public health crisis with far-reaching consequences. With the spread of AR, previously treatable infections have become challenging, and often impossible, to treat. According to the Center for Disease Control’s recently released 2019 AR Threat Report, each year in the United States there are more than 2.8 million AR infections, resulting in 35,000 deaths. Even though these numbers have decreased by approximately 18% since 2013, the numbers are unacceptably high.

Antibiotics are life-saving medications when used in the correct context. Any time antibiotics are used, a strain of bacteria can develop resistance. Since the resistant bacteria aren’t killed by the antibiotic, they will continue colonizing. Continued use of the same antibiotic will select for resistant strains and may reduce numbers of protective bacterial strains. Bacteria are incredibly clever and are able to rapidly share resistance genes within and between species, leading to resistance in bacteria that have never encountered an antibiotic.

Developing novel antibiotics is a huge undertaking and, while pharmaceutical companies are working on new classes of antibiotics, it is clear we are not equipped to keep pace with the rapidly adapting microbial world.

Mechanisms of Antibiotic Resistance
Antibiotic resistance occurs when microorganisms develop the ability to overcome the antibiotics designed to kill them. Bacteria have numerous strategies to resist antibiotics. Gram-negative organisms tend to display more AR strategies than do gram-positive organisms. This is mostly due to the presence of a double cell membrane. The periplasmic space between the two membranes of gram-negative organisms acts as a protective holding chamber, giving the bacteria a chance to react before the antibiotics can access the inside of the cell.

Testing for AR genes can help to characterise resistant infections and can aid in selecting effective therapies. Some of the key AR strategies are detailed below.

Preventing Access of Antibiotics to the Inside of the Cell
Altered uptake – Organisms are able to alter the permeability of their cell membrane, making it more difficult for antibiotics to enter the cell.

Efflux pumps – Trans-membrane pumps that are able to recognise antibiotics and other substances and rapidly pump them out of the cell. Both gram-positive and gram-negative organisms are able to use efflux pumps. In gram-positive organisms, efflux pumps must work much more rapidly to protect the cells from antibiotic damage, because they do not have a protective double membrane.

Target Modification
Each antibiotic class has a specific target within a microorganism (nucleus, DNA, RNA, proteins, cell wall etc.). Mutations can alter the structure of the target so that the antibiotics can no longer bind to and act on the target. Microorganisms can also protect antibiotic targets and/or make them obsolete to cell function.

Enzymatic Degradation
Enzymes are proteins that are able to break down antibiotics. The most notable enzymes are β-lactamases, which are used to break down the β-lactam (penicillin) family of antibiotics.

Quorum Sensing
When the population of bacteria reaches a critical level, they release signalling molecules into their environment. These molecules, known as auto-inducers, can precipitate a number of different effects including biofilm formation, gene transfer, virulence or toxin production.

The Use of Botanicals Against Antibiotic-Resistant Bacteria
The world of botanical medicine offers promising potential in the fight against AR bacteria. Herbs have been used traditionally to treat infections for hundreds of years. While many herbs are used empirically against bacterial infection, others have extensive research on the individual constituents and actions against bacteria.

When it comes to treating antibiotic resistance in the GI tract, there are two main strategies that can be used;

choosing botanicals for their direct antimicrobial effects AND
choosing botanicals as synergists to directly target AR mechanisms.
Below are listed some key antimicrobial botanicals and their mechanisms of action.

Botanicals as Antimicrobial Agents
There are many herbs that have evidence of antimicrobial activity, both locally and systemically. The following is a shortlist of herbs that are especially effective as local antimicrobials. When it comes to multi-drug resistant bacteria, combining multiple whole-herb extracts is a beneficial strategy.

Berberine-containing herbs – Mahonia aquifolium, Hydrastis canadensis, Coptis chinensis etc.

Berberine herbs are very effective antimicrobials. Standardized berberine extracts are readily available. However, research indicates that whole-herb extracts have stronger antimicrobial activity than standardized berberine.

Wormwood – Artemisia absinthium

Artemisia is a very effective antimicrobial with a long history of traditional use against bacteria, fungi and parasites.

Garlic – Allium sativum

Allium has proven effectiveness as an antimicrobial. Greater effects are seen with fresh crushed garlic than with water extraction.

Old Man’s Beard – Usnea barbata

Usnea and other lichens have very strong antimicrobial effects against both gram-positive and gram-negative bacteria, especially when used as a strong ethanol extract.

Clove – Syzygium spp.

Syzygium is effective against numerous gram-negative and gram-positive bacteria in both ethanol and water extractions.

Botanicals as Targeted Synergists in Combination Therapy
The following botanicals can be used in strategic combination with antibiotics or antimicrobial herbs. The following herbs have been shown to have specific action against AR mechanisms. The use of synergists can decrease the amount of antibiotic needed to be effective against bacteria. Synergists can also be used as adjuncts to herbal antimicrobial therapy. Note that some species of herb fall under more than one category. This is because each plant contains hundreds of individual constituents, which may have varied activity against bacteria and the microbial world.

Efflux Pump Inhibitors
Licorice – Glycyrrhiza glabra
Milk Thistle – Silybum marianum
Green tea – Camellia sinensis
Sweet flag – Acorus calamus
Wormwood – Artemesia absinthium
Chinese skullcap – Scutellaria baicalensis
β-Lactamase Inhibitors
Chinese skullcap – Scutellaria baicalensis
Green tea – Camellia sinensis
Quorum Sensing Inhibitors
Green tea – Camellia sinensis
Sweet flag – Acorus calamus
Rosemary – Rosmarinus officinale
Putting it Together
While antibiotic therapy is a necessary and very effective solution for most bacterial infections, they have proven to be insufficient against AR strains. Botanical therapy offers promising solutions to combat multi-drug resistant bacteria. Bactericidal herbs can be used either instead of or in addition to antibiotic therapy. In addition to this, whole herb extracts can be used synergistically to make antibiotic or herbal antimicrobial therapy more effective. Testing for AR genes can help to guide treatment. Antibiotics and botanicals can be selected strategically based on known and suspected AR mechanisms.


Research and Writing by Dr Amy Rolfsen
Dr Amy Rolfsen is a naturopathic doctor and medical consultant. Her areas of clinical interest and expertise are; women’s wellness, children’s health, immunology and gastrointestinal health.



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