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Title

Widening the antimicrobial spectrum of esters of bicyclic amines: In vitro effect on gram-positive Streptococcus pneumoniae and gram-negative non-typeable Haemophilus influenzae biofilms

AuthorsRoig-Molina, Emma; Domenech, Mirian ; Retamosa Hernández, María Gracia; Nácher-Vázquez, Montserrat ; Rivas, Luis ; Maestro, Beatriz; García, Pedro ; García, Ernesto ; Sanz, Jesús M.
KeywordsBroad-spectrum antimicrobials
EBAs
Membrane permeability
Mixed biofilms
Issue DateJan-2019
PublisherElsevier
CitationBiochimica et biophysica acta. General subjects 1863(1):96-104 (2019)
AbstractAntibiotic resistance is a global current threat of increasing importance. Moreover, biofilms represent a medical challenge since the inherent antibiotic resistance of their producers demands the use of high doses of antibiotics over prolonged periods. Frequently, these therapeutic measures fail, contributing to bacterial persistence, therefore demanding the development of novel antimicrobials. Esters of bicyclic amines (EBAs), which are strong inhibitors of Streptococcus pneumoniae growth, were initially designed as inhibitors of pneumococcal choline-binding proteins on the basis of their structural analogy to the choline residues in the cell wall. However, instead of mimicking the characteristic cell chaining phenotype caused by exogenously added choline on planktonic cultures of pneumococcal cells, EBAs showed an unexpected lytic activity. In this work we demonstrate that EBAs display a second, and even more important, function as cell membrane destabilizers. We then assayed the inhibitory and disintegrating activity of these molecules on pneumococcal biofilms. The selected compound (EBA 31) produced the highest effect on S. pneumoniae (encapsulated and non-encapsulated) biofilms at very low concentrations. EBA 31 was also effective on mixed biofilms of non-encapsulated S. pneumoniae plus non-typeable Haemophilus influenzae, two pathogens frequently forming a self-produced biofilm in the human nasopharynx. These results support the role of EBAs as a promising alternative for the development of novel, broad-range antimicrobial drugs encompassing both Gram-positive and Gram-negative pathogens.
Description26 p.-6 fig.-3 tab.
Publisher version (URL)https://doi.org/10.1016/j.bbagen.2018.10.001
URIhttp://hdl.handle.net/10261/170961
DOI10.1016/j.bbagen.2018.10.001
ISSN0304-4165
Appears in Collections:(CIB) Artículos
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