Interaction between lichen secondary metabolites and antibiotics against clinical isolates methicillin-resistant Staphylococcus aureus strains

Phenylboronic Acid Derivatives as Validated Leads Active in Clinical Strains Overexpressing KPC‐2: A Step against Bacterial Resistance

“…Checkerboard microdilution assay:T he in vitro interactions between the antibiotics used for the double-disk assay and the boronic acid compounds were investigated by at wo-dimensional checkerboard microdilution assay by using 96-well microtitration plates, as previously described. [40] Assays were conducted against the E. coli BL21 (DE3) pET-24a-bla KPC-2 and against six K. pneumoniae clinical strains isolated from different patients at the Hospital Universitario Son Espases, Palma de Mallorca, Spain. The microtiter plates were incubated at 37 8Cf or 18 h. The growth in each well was quantified spectrophotometrically at l = 595 nm by am icroplate reader iMark, BioRad (Milan, Italy).…”

Protolichesterinic acid enhances doxorubicin-induced apoptosis in HeLa cells in vitro

“…Many different biological properties, such as anti-inflammatory, antimicrobial, antioxidant, cytotoxic and antiproliferative activities, have been associated to lichen compounds [1][2][3][4]. In the recent years, the interest in the pharmaceutical potential of lichen metabolite [5,6] is increasing even if the biological activity and therapeutical potential of relatively few compounds have been deeply investigated.…”

Symbiosis-inspired approaches to antibiotic discovery

“…123 Biosynthetic pathways associated with production of these NPs include PKS systems (affording mono-cyclic phenols, depsides, depsidones, depsones, dibenzofurans, xanthones, naphthoquinones and anthraquinones, macrocyclic lactones, aliphatic acids, and others), the mevalonic acid pathway giving rise to steroids, carotenoids and related compounds as well as the shikimic acid pathway (giving rise to amino acid derivatives, and related shikimate-derived NPs). 125 Lichens and their assorted biosynthetic capabilities have been recently reviewed 122, 123, 125, 126 though a number of advances support the ever-increasing interest in these symbiotic systems as beacons of antimicrobial drug discovery. Particularly notable recent findings in which precise lichen structures are known and/or associated with specific antimicrobial actions are: i) work by Lou and co-workers to rigorously elucidate the structures and bioactivities of NPs from Aspergillus versicolor isolated from the lichen Lobaria quercizans leading to the identification of 14 new NPs (as exemplified by diorcinols F–H, and a number of bisabolane sesquiterpenoids such as the hydroxysydonic acid congeners shown below) as well as 15 known agents; though a focus on cytotoxic activities was reported for many of these diverse structures a number were also shown to possess antifungal activities, 127 ii) recent efforts to unveil synergistic interactions between established and clinically relevant antimicrobials such as gentamycin and levofloxacin in combination with assorted (and previously characterized) lichen-derived NP such as lobaric, α-collatolic, protolichesterinic, perlatolic and epiforellic acids from Chilean environments (inclusive of Antarctic regions) giving rise to antibacterial activities against MRSA, 125, 128 iii) studies of usnic acid, arguably the most well studied of all known lichen-derived NPs, indicating its ability to inhibit biofilm forming processes essential to the pathogenicity of Streptococccus pyrogenes , 129 iv) the revelation that the lichen endophyte-derived NP pyridoxatin displays antifungal activity against Candida albicans by interfering with ergosterol production essential to biofilm synthesis, 130 v) the recent discovery that cultured mycobionts from Sarcographa tricosa lichens (isolated from trees in Vietnam) produce eremophilane-type sesquiterpenes 3- epi -petasol, dihydropetasol and sarcographol, in addition to a number of other previously known eremophilane sesquiterpenes for which a wide assortment of antimicrobial activities have been well established, 131 vi) the revelation that norlichexanthone a well-known lichen-derived PKS product, displays antibacterial activity against S. aureus by virtue of its ability to reduce the expression of hla and RNAIII while also inhibiting DNA associations with the key regulatory protein AgrA—the result being reduced production of key virulence factors and impaired biofilm formation, 132 and vii) recent studies of the Letharia vulipina metabolite vulpinic acid that reveal this lichen-derived NP to express activity against MRSA via cell membrane and cell division targeting; these findings were in support of earlier studies by St. Clair et al showing that extracts of 36 species of lichens displayed often potent activity against four different pathogenic bacteria, of these Letharia vulipina extracts composed almost exclusively of vulpinic acid proved to be the most broadly antibacterial.…”