Terpenes (general)

Fighting Antiobiotic-Resistant Disease with Terpenes

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Written by Sabina Pulone

The discovery of antibiotics revolutionized therapeutic approaches against microbial infections and undoubtly saved millions of people. In the mid-20th century, antibiotics were seen as magic bullets capable of selectively inhibiting microbial growth responsible for illness without affecting the patient. [1] Despite this general feeling, there were already observations regarding the possible induced resistence to antibiotics if overused. [2]

The increased demand over time of antibiotic prophylactic treatments over different types of industrial sectors (agriculture, animal husbandry, etc.) led to an excessive and sometimes irresponsible use of these valuable antimicrobial molecules. This contributed to the development of resistant strains, together with the natural selection process where nature empowers bacteria with a degree of low-level resistance. [1]

There is always more need for new molecules capable of inhibiting bacterial growth because of the increasing appearance of resistant strains and the related serious public health concequences that follow. Within natural molecules, great attention has been placed on plant-derived terpenes, which could be developed as a new class of antimicrobial molecules exhibiting synergistic effects against multi-resistant bacterial strains. [3]

Because of terpenes’ low yield from natural sources, some synthetic or semi-synthetic derivatives with potentiated biological properties have been developed. Terpenes are molecules formed by “head-to-tail” junction of isoprene units to form cyclic or acyclic structures. Depending on the number of carbon atoms, they are divided into monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), etc.

Monoterpenes are the main volatile constitutents of essential oils. These molecules, in particular those bearing oxygenated substituents (thus capable of making hydrogen bonds; e.g., thymol, carvacrol, menthol, etc.), have shown great activity against several Gram (+) and Gram (-) bacteria. [4]

The acyclic and alcohol functionalized monoterpenoid geraniol has been extensively studied against multidrug resistant (MDR) microorganisms: studies on Helichrysum italicum (curry plant) have shown geraniol as the most active component of the essential oil capable of modulating antibiotic resistance in bacteria thorugh efflux pump inhibitory (EPI) activity. [5]

The combination of sesquiterpenes and various antibiotics like tetracycline, erithromycin, and penicillin was observed to positively enhance the antimicrobial activity of these medicaments against resistant strains of Staphylococcus aureus but not Escherichia coli.

A great number of diterpenes also showed improved pharmacological activity of antibiotics on MDR bacteria: studies on the diterpene labdane from Zingiber monthanum (cassumunar ginger) against clinical isolates of MDR S. aureus and methicillin-resistant S. aureus (MRSA) highlighted potent antimicrobial activity with minimum-inhibitory concentrations (MIC) ranging from 46 to 93 μg/ml. [6]

Many other studies on this class of fragrant natural molecules point out their great ability to reduce bacteria proliferation and face antibiotic resistant diseases. [3] Hence terpenes will be at the basis of the development of new kind of antimicrobial agents capable of targeting antibiotic resistant diseases.

 

References:

[1] Zaman SB, et al. A review on antibiotic resistance: alarm bells are ringing. Cureus. 2017.  doi:10.7759/cureus.1403 [Journal Impact Factor = n/a] [Times cited = 280 (Semantic Scholar) ]

 

[2] Aminov RI, et al. A brief history of the antibiotic era: lessons learned and challenges for the future. Frontiers in Microbiology. 2010. doi:10.3389/fmicb.2010.00134 [Journal Impact Factor = 5.640 ] [Times cited = 750 (Semantic Scholar)]

 

[3] Cappiello F, et al. The reevaluation of plant-derived terpenes to fight antibiotic-resistant infections. Antibiotics. 2020;9(6):325. doi:10.3390/antibiotics9060325
[Journal Impact Factor = 2.649] [Times cited = 9 (Semantic Scholar)]

 

[4] Griffin SG, et al. The role of structure and molecular properties of terpenoids

in determining their antimicrobial activity. Flavour and Fragr J. 1999;14:322–332. [Journal Impact Factor = 2.576] [Times cited = 422 (Semantic Scholar)]

 

[5] Lorenzi V, et al. Geraniol restores antibiotic activities against multidrug-resistant isolates from gram-negative species. Antimicrobial Agents and Chemotherapy. 2009;53(5):2209–2211. doi:10.1128/aac.00919-08 [Journal Impact Factor = 4.715] [Times cited = 248 ]

 

[6] Siddique H, et al. Terpenes from Zingiber montanum and their screening against multi-drug resistant and methicillin resistant Staphylococcus aureus. Molecules. 2019;24(3):385–.doi:10.3390/molecules24030385 [Journal Impact Factor = 4.411] [Times cited = 4 (Semantic Scholar)]

 

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Sabina Pulone

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