Sesquiterpene Farnesol Contributes to Increased Susceptibility to β-Lactams in Strains of Burkholderia pseudomallei

Abstract

cThis study aimed to evaluate the in vitro combination of farnesol and ␤-lactams against Burkholderia pseudomallei. A total of 12 ␤-lactamase-positive strains were tested according to CLSI standards. All strains were inhibited by farnesol, with MICs ranging from 75 to 150 M. The combination of this compound with ␤-lactams resulted in statistically significant ␤-lactam MIC reduction (P < 0.05). This study provides new perspectives for the use of farnesol combined with ␤-lactam antibiotics against strains of B. pseudomallei. Burkholderia pseudomallei is a Gram-negative bacillus that causes melioidosis, a severe and potentially fatal disease endemic to Southeast Asia and hyperendemic to Northern Australia (2, 17).Some antibiotics currently recommended for the treatment of melioidosis are ceftazidime, imipenem, meropenem, amoxicillinclavulanate, cefoperazone-sulbactam, trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol (17). However, B. pseudomallei has developed resistance to these drugs (14,15,17,18); hence, it is necessary to search for new agents that are effective against this microorganism.The sesquiterpene alcohol farnesol is present in many essential oils of plants, such as Pluchea dioscoridis and Pittosporum undulatum, possibly to protect against attack by predators (5, 12). Farnesol has also been detected in the supernatant of Candida albicans broth cultures, as it is a quorum-sensing molecule of this fungal species (11).Moreover, farnesol is able to inhibit some microorganisms, such as Staphylococcus aureus, Streptococcus mutans, and Paracoccidioides brasiliensis, indicating its potential antimicrobial activity (4, 6-9), which has also been demonstrated against bacterial biofilms (16). Some studies have shown the ability of farnesol to increase the susceptibility of microorganisms to antimicrobials, indicating a possible applicability as an adjuvant drug (7). Brehm-Stecher et al. (1) reported increased susceptibility of S. aureus to ciprofloxacin, clindamycin, erythromycin, gentamicin, tetracycline, and vancomycin, as well as of Escherichia coli to polymyxin B, when these drugs were combined with farnesol. Thus, the objective of this study was to evaluate the in vitro activity of farnesol, alone and in combination with ␤-lactams, against strains of B. pseudomallei.We used 12 strains of ␤-lactamase-producing B. pseudomallei, stored in the Laboratory of Emerging and Reemerging Pathogens (LAPERE) of the Federal University of Ceará. Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, methicillinresistant Staphylococcus aureus (MRSA), and ␤-lactamase-negative S. aureus were used as experimental controls. Susceptibility testing was performed by the broth dilution method, as standardized by CLSI, described in document M07-A8 (3). The medium used was Mueller-Hinton broth (Difco, USA), and the concentration ranges were from 0.25 to 128 mg/ml for amoxicillin (Roche, Brazil), from 0.25/0.125 to 128/64 mg/ml for amoxicillin-clavulanate (Roche, Brazil), from 0.0312 to 16 mg/ml for imipenem (Ro...

Effect of Farnesol on Growth, Ergosterol Biosynthesis, and Cell Permeability in Coccidioides posadasii

“…Several studies have confirmed the inhibitory effect of farnesol on the growth of several bacteria (12,13,27). More recently, many studies have described the activity of farnesol against different species of fungi (15)(16)(17)(18).…”

Selected Compounds Structurally Related to Acyclic Sesquiterpenoids and Their Antibacterial and Cytotoxic Activity

“…Brilhante et al showed that farnesol had an inhibiting activity alone and in combination with antifungal agents against strains of dimorphic fungi from the genus Coccidioides and against Candida spp. clinical isolates [4,5]. Nerolidol shows a toxic effect against, inter alia, Salmonella enterica, Staphylococcus aureus, Escherichia coli and Aspergillus niger, and increases the antibacterial activity of antibiotics [6,7].…”

“…Farnesol, which is present in many creams and nourishing agents, has a bacteriostatic effect against bacteria that can cause acne (Staphylococcus aureus, Staphylococcus epidermidis) and does not affect naturally occurring microflora on the skin [1]. It blocks the formation of biofilm by the drug-resistant strains of Staphylococcus aureus and acts synergistically with antibiotics [2][3][4]. Brilhante et al showed that farnesol had an inhibiting activity alone and in combination with antifungal agents against strains of dimorphic fungi from the genus Coccidioides and against Candida spp.…”

Histoplasma capsulatum in planktonic and biofilm forms: in vitro susceptibility to amphotericin B, itraconazole and farnesol

“…Many studies have sought new compounds with antimicrobial activity. The sesquiterpene farnesol has gained prominence due to its high antimicrobial activity against bacteria and fungi (Inoue et al, 2004;Jabra-Rizk et al, 2006;Brilhante et al, 2012Brilhante et al, , 2013. Its potential antifungal activity has already been demonstrated against different species of Candida and Cryptococcus , as well as against Coccidioides posadasii and Paracoccidioides brasiliensis (Derengowski et al, 2009).…”