Antimicrobial Endophytes in Echinacea, Olive and Manuka

While plants are being extensively explored for new therapeutic properties and pharmacological activities, the communities of live fungi and bacteria known as endophytes that live between living plant cells, are also now being regarded as having many useful potential medicinal applications. Ironically, in recent years it is these microorganisms associated with plants rather than plants themselves, which seem to be receive much research interest.

Endophytes are microorganisms that live within a plant for at least part of their life cycles, without causing apparent disease or infections in the plant. Different endophytes seem to have affinities for particular plants, with which they have distinctive and cherished but complex interactions while each of them grows. They are for instance known to sometimes enhance host growth and nutrient gain, improve the plant’s ability to tolerate various types of stressors, and enhance the its resistance to insects and pests. The rrelationships that these bacteria and fungal communities have with their host plant varies from symbiotic to parasitic, to bordering on pathogenic.
Some very unusual and valuable bioactive substances are sometimes produced by these endophytes, such as alkaloids, phenolic acids, quinones, steroids, saponins, tannins, and terpenoids, and these are increasingly being recognized as sources of novel compounds which may help to maintain or solve not only the plant’s health challenges, but can also have applications in human and animal health problems.
Over the past few decades, some highly medicinal compounds produced by endophytic microbes lead to novel drug development. These include Taxol (paclitaxol), a complex diterpene alkaloid produced by the endophyte Metarhizium anisopliae found in the bark of the Pacific Yew (Taxus brevifolia) tree, and one of the most promising anticancer agents ever developed. Also streptomycin, an antibiotic produced from the bacterial endophyte Streptomyces.

Other endophytes possess antibacterial activities which may be useful in treating various infections, and in a world where antibiotic resistance is becoming a major public health threat, these are obviously of great interest. Exploring and bioprospecting these for potential antimicrobial compounds may well yield valuable new natural products or drugs to help in the fight against resistant organisms(1,2,3,4).

It now seems that bacterial communities colonizing Echinacea purpurea contribute to its well-known immune enhancing activity(5). American researchers have reported that Echinacea’s stimulating activity on monocytes (a type of white blood cell involved in engulfing and destroying harmful microbes), could be solely if not partially accounted for by the activities and prevalence of Proteobacteria, a family of bacteria found in the bacterial community associated with this medicinal plant.
A screen of 151 different endophytic bacteria isolated from three different compartments of Echinacea purpurea, revealed that several bacteria isolated from the roots are strong inhibitors of Burkholderia cepacia complex bacteria, a serious threat particularly in immune-compromised cystic fibrosis patients(6). One of these bacterial strains also showed antimicrobial effects against Acinetobacter baumannii, a pathogenic bacteria mainly associated with hospital-acquired infections, and Klebsiella pneumoniae, also increasingly incriminated in hospital infections(7). Interestingly, the type of bacteria and their antimicrobial effects varied considerably, according to which part of the plant (root, stem, leaves etc) they were associated with. This has resemblances to different plant parts of Echinacea having different phytochemical and thus pharmacological activities, such as Echinacea roots being richest in alkylamides and thus anti-inflammatory activities.

Endophytic fungi including Penicillium commune and Penicillium canescens (related to the Penicillium notatum mould from which the first antibiotic penicillin originated), have also been isolated from the leaves of olive (Olea europaea) trees, and several of these have also shown antibacterial as well as antifungal activities in recent work(8).

Finally, a rich endophyte community has recently been identified by Lincoln University researchers for the New Zealand native plant Manuka (Leptospermum scoparium). A total of 192 culturable bacteria were recovered from leaves, stems and roots, including some showing activity against the bacterial pathogen, Pseudomonas syringae pv. actinidiae(9), otherwise known by Kiwifruit growers as Psa. With Psa being a serious risk to the health of the Kiwifruit vine, it could be that these endophytic bacteria found within Manuka will make a useful contribution to ensuring the future health of the Kiwifruit industry.
While very few of all of the world’s plants have had their complete complement of endophytes studied, these are just three well established medicinal plants from which some highly active cohabitating bacteria and fungi have been sourced. Undoubtedly this area of research will receive much more attention due to growing concerns about antibiotic resistance, as there would seem to be a huge opportunity to find new and interesting endophytes among the wealth of different plants growing not only in soil, but also in waterways and oceans.
Refs:
1. Alvin A et al, Microbiol Res 2014; 169(7-8)L483-495.
2. Martinez-Klimova E et al, Biochem Pharmacol 2016; Oct 27.
3. Kealey C et al, Biotechnol Lett 2017; Mar 8 (epub ahead of print)
4. Tanwar A et al, Microbiol Path 2016;101:76-82
5. Haron MH et al, Planta Med 2016; 82(14):1258-1265.
6. Chiellini C et al, Microbiol Res 2017; 196:34-43.
7. Presta L et al, Res Microbiol 2017; 168(3):293-305.
8. Malhadas C et al, World J Microbiol Biotechnol 2017; 33(3):46.
9. Wicaksono WA et al, PLoS One 2016; 11(9):e0163717.

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Calendula for venous ulcers and thrush

Preparations made from flowers of the English or Pot Marigold (Calendula officinalis), a well-known garden plant, are widely recommended and used by western medical herbalists for minor cuts, grazes, and slow healing wounds, where an antiseptic and healing action is required. The European Medicines Agency has also approved Calendula as a traditional medicinal product for the treatment of minor skin inflammation, and as an aid in the healing of minor wounds.

However, apart from two clinical trials showing benefits from a Calendula ointment to treat dermatitis secondary to radiotherapy treatment in cancer patients (1, 2), few human clinical trials have been published.

Brazilian researchers recently conducted a clinical trial to evaluate the effectiveness of Calendula extract in the treatment of non-healing venous leg ulcers (3). Treatment consisted of a twice daily spray application of a hydro glycolic extract of Calendula, or the standard hospital procedure which included the use of collagenase, the antibiotic chloramphenicol, and 1% silver sulfadiazine cream. Both treatments were given for a period of 30 weeks or until ulcers healed, and nursing staff examined and assessed patients every two weeks, during which the wound area was measured and clinically evaluated.

Swabs were collected from the wounds before starting treatment, and these showed Staphylococcus aureus to be the predominant microorganism in both the control and Calendula groups, with Pseudomonas spp., Klebsiella spp., and Escherichia coli being found in the wounds of some patients. The size and duration of ulcers prior to treatment was similar in both groups, and patients had an average age of 68 years in the control group of 19 patients, and 63 in the Calendula treated group of 38 patients.

After 12 weeks treatment, 39% of Calendula-treated wounds were completely closed, but none in the standard treatment control group. After 30 weeks treatment, 72% achieved complete wound closure, while only 32% were closed in the control group. An average of 12 weeks was needed for healing to occur in the Calendula-treated group, but 25 weeks in the control group. No adverse events were observed during the Calendula treatment.

Favourable outcomes were also achieved in a Serbian clinical trial which involved 21 venous ulcer patients who applied Calendula ointment twice daily for 3 weeks (4). Calendula treatment reduced the total surface of the ulcers by an average of 41.7%, but only by 14.5% in the control group of 13 patients treated with saline dressings. Complete wound closure was achieved in four patients treated with Calendula.

These two studies show a significant acceleration of chronic venous ulcer wound healing through twice daily application of topical products made using Calendula flowers. While a 3 week treatment period was beneficial, continuing this for longer periods is recommended to achieve optimal results.

Beneficial effects of Calendula cream for the treatment of vaginal Candidiasis (thrush), were also reported from a recent Iranian study involving 150 women aged 18-45 years(5). Participants used a 5-g vaginal applicator of Calendula or clotrimazole (an antifungal drug) cream for seven nights before going to bed, then were assessed at two post treatment time points.

Compared to the clotrimazole group, fewer women in the Calendula group tested negative for Candidiasis at 10–15 days following treatment (49% vs 74%), although both treatments had similar effects at improving clinical signs and symptoms and sexual function. At a 30-35 day post treatment follow up, however, signs and symptoms were less severe in the Calendula treated group, and women treated with Calendula were significantly less likely to have suffered a recurrence of Candidiasis, than those treated with clotrimazole.

These results suggest that a seven day course of intravaginal calendula cream is safe and can be effective for the treatment of vaginal Candidiasis, but seems to have a delayed effect compared to clotrimazole. However, Calendula use may have better long term outcomes such as a lower risk of recurring infections, even after a 7 day course.

While a longer duration of Calendula use may have greater effectiveness in the treatment of vaginal Candidiasis, particularly as resistance is increasing to clotrimazole and other antifungal drugs, this trial provides encouraging data to support its use for this annoying problem experienced by a large number of women.

Clearly the impressive healing capabilities held by the attractive and bee-loving flowers of this easy to grow plant, extend beyond minor cuts and grazes, to include more chronic and debilitating conditions such as venous ulcers and vaginal thrush.

Refs:

  1. Pommier P et al, J Clin Oncol 2004; 22(8):1447-1453.
  2. Schneider F et al, Rev Esc Enferm USP 2015; 49(2):221-228
  3. Buzzi M et al, J Wound Care 2016; 25(12):732-739
  4. Duran V et al, Int J Tissue React 2005
  5. Saffari E et al, Women & Health 2016; Nov 23:1-16