Usnic acid is one of the most abundant secondary metabolites produced by lichen genus such as Usnea sp. Usnic acid antibacterial mechanism of action study has shown to target multiple cell components and also showed synergy with different antibiotics against multi-drug resistant bacteria such as methicillin resistant Staphylococcus aureus (MRSA). Drug-resistant bacteria continue to grow and defeat the drugs in use for both humans and animals. Therefore, use of alternative drugs from natural sources such as usnic acid can fight infections and may improve therapeutic efficacy while lowering side effects of antibiotics. Considering the emergence of resistant strains, this review is intended to summarize potential targets of usnic acid, with a focus on developing novel therapeutic agents against MRSA.

Anti-staphylococcal activity, Methicillin resistant Staphylococcus aureus, Usnic acid, Usnea spp.

Gangwar B, Kumar S, Darokar MP (2022) Usnic Acid: A Potential Natural Anti-Staphylococcal Agent. Ann Clin Pathol 9(1): 1156.

UA: Usnic acid, MRSA: Methicillin resistant Staphylococcus aureus, S. aureus: Staphylococcus aureus, MIC: Minimum Inhibitory Concentration, WHO: World Health Organization

Staphylococcus aureus is a major pathogen and member of the ‘ESKAPE’ group of pathogens classified by WHO. S. aureus in an opportunistic pathogen that can cause skin infections. It may also cause more deadly diseases such as pneumonia, carditis, and septicemia in immunocompromised patients. Furthermore, the emergence of drug resistant strains to last resort of antibiotics such as vancomycin is a big challenge in the modern age of medicine. Developments of drug resistance pose crisis to combat infections all around the world. S. aureus has acquired several mechanisms including efflux transport, target modification, and enzymatic degradation to overcome antibiotics stresses. In addition, biofilm is also a big cause of antibiotics resistance reported in S. aureus.

Emergence of various drug-resistant strains are becoming increasingly difficult to treat by conventional medicine. Antibacterial potential of natural compound usnic acid (UA) against pathogens prompted us to collect information about anti-staphylococcal properties and action mechanism of UA that was first mentioned in the literature in the 1950s, with the aim of finding new strategies against MRSA. It is naturally produced by Lichens that form when algae or cyanobacteria interact with fungi. About 600 species have been found in the Usnea genus [1,2]. In lichens, UA is found in the form of (+)- and (-)- enantiomers, which have different biological activities. (+)- UA have more antibacterial action than (-)-UA against bacterial pathogens. UA was also found to be effective against a wide range of serious gram-positive pathogens, including Enterococcus faecalis, Enterococcus faecium, and clinical isolates of methicillin resistant Staphylococcus aureus. More studies for antimicrobial mechanism of action of UA may pave the way for further research in the future. The purpose of the present review is to focus on UA and its potential role in medical and pharmaceutical importance.

Chemical features of Usnic acid

UA is a bioactive furandione compound (2,6-diacetyl-7,9- dihydroxy-8,9b-dimethyl-1,3(2H,9bH)-dibenzo-furandione), with the formula C18H16O7 . It is mainly found as a secondary metabolite (yellowish pigment) in lichens and was isolated in 1844. It exists in two natural enantiomers (+)- and (-)-UA and it is commercially available. UA is almost insoluble in water, although the solubility of UA is higher in acetone (1.21 g/100 mL), ethyl acetate (0.88 g/100 mL), and ethanol (0.77 g/100 mL) [3].

Uses of Usnic acid in traditional medicinal systems

The most used lichen species are Usnea subfloridana, Usnea barbata, and Usnea hirta [4]. Lichen has been used for therapeutic purposes in many traditional systems for the treatment of tuberculosis and skin diseases. Later, it was found to have antimicrobial [5], antifungal [6], antiviral [7], antiinflammatory [8], analgesic, antipyretic [9], antiparasitic [10], antitumor [11], enzymatic inhibition [12] and gastroprotective [13] (Figure 1).

Figure 1 Usnic acid showed different activity in traditional medicine system.

In addition, the ancient Greeks used Usnea sp. extract for insomnia, hair growth, dandruff, internal and external bleeding, nausea, jaundice, diarrhea, chickenpox, cold, whooping cough, cracked skin, and uterine infection [14]. In European countries, Usnea sp. was utilized as an antibacterial agent to treat fever, pulmonary pain, tuberculosis, wounds, athlete’s foot, and antibiotic-resistant infections [15]. Lichens have been mentioned in pharmacopoeias because of their therapeutic application in traditional phytotherapy [16].

Usnic acid as anti-staphylococcal agent

UA has many known therapeutic properties, with most reports since its discovery focused on its antibacterial potential and particularly on its mechanisms of action against an increasing number of strains resistant to conventional antibiotics. Due to the current problem of Methicillin-resistant S. aureus, UA is here listed for activity based on Minimum inhibitory concentration (MIC) against S. aureus clinical isolate. The in-vitro susceptibility of S. aureus clinical isolates as well as strains sensitive to (+)- and (-)- UA has been previously reported (Table 1).

Table 1: Minimum inhibitory concentration of usnic acid reported against different strains of Staphylococcus aureu

 Abbreviations: UA: Usnic acid, MIC: Minimum inhibitory concentration, MRSA: Methicillin resistant Staphylococcus aureus; MSSA: Methicillin sensitive Staphylococcus aureus, S. aureus: Staphylococcus aureus

Both isomers have been reported for strong activity against clinical isolates of S. aureus, including methicillin resistant strains [17,18].

Mechanism of action for anti-staphylococcal activity

UA is reported to have potent antibacterial activity against Gram-positive bacteria [19-28]. UA was shown to inhibit RNA and DNA synthesis and blocks DNA replication and elongation in S. aureus [29]. UA is suggested to pass through cell membranes due to their non-polar chemical properties [24,30-31]. A summary of mechanism of action against S. aureus strains is listed in Table 2.

The research of UA as an antibacterial agent started at the turn of the 20th century. This review article discusses the antibacterial especially anti-staphylococcal properties of UA as well as its uses in various traditional treatments. Although, UA has shown potential antibacterial activity against different grampositive bacteria including MRSA, yet more advance in-vitro and in-vivo studies are required to decipher underlying molecular mechanisms to develop it as pharmaceutical.

All authors acknowledge the support of Director, CSIR-CIMAP in Lucknow, India, and Dr. Bhavana Gangwar, also acknowledges the Indian Council of Medical Research (ICMR) in New Delhi.

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