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

Abstract

equally to this work. Highlights  Esters of bicyclic amines (EBAs) destabilize the bacterial membrane  EBAs trigger the premature autolysis of Streptococcus pneumoniae by LytA autolysin  EBAs disrupt mixed biofilms formed by S. pneumoniae and Haemophilus influenzae  Broad-spectrum effect of EBAs is useful to fight antimicrobial resistance Abstract Antibiotic 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.

Antibacterial effect of TiO2 modified with poly-amidoamine dendrimer – G3 on S. aureus and E. coli in aqueous solutions

“…Gram negative bacteria absorb more amine in their surfaces than gram positive ones so that's why charge density of gram negative is higher (Charles et al 2012). The obtained results were supported by previous studies (Nazari et al 2019;Roig-Molina et al 2019).…”

Phytochemical Composition and Antibacterial Activities of the Ethyl Acetate Leaf Extract of Ocimum basilicum

“…Fatty acids may also interact with cellular membranes thereby causing leakage of molecules from the cells, reduction of nutrient uptake or inhibiting cellular respiration [42]. Amines eluted from the extract include 9-Thiabicyclo effects [39,40]. Aldehydes with long chain fatty alcohols such as E-11(13-Methyl) tetradecen-1-ol acetate, Tridecenol < 2E-> and tetradecanal have been shown to have antibacterial activities on S. aureus [41].…”

“…non-6-en-2-amine, N-methyl-, endo-; 1,2,4-Triazol-3-amine, 5-(1,3,5-trimethyl-4-pyrazolyl) amino-and 2-Methoxyamphetamine. Bicyclic amines have been documented to have antimicrobial and antiparasitic effects[39,40]. Aldehydes with long chain fatty alcohols such as E-11(13-Methyl) tetradecen-1-ol acetate, Tridecenol < 2E-> and tetradecanal have been shown to have antibacterial activities on S. aureus[41].…”

Combination of Cefditoren and N -acetyl- l -Cysteine Shows a Synergistic Effect against Multidrug-Resistant Streptococcus pneumoniae Biofilms

“…Most of the information available so far is related to S. pneumoniae ( 6 ). The inherent tolerance of these communities to antibiotic therapy and the host immune system is well known ( 7 – 10 ). Biofilms may be established on medical devices, such as indwelling intravenous catheters or endotracheal tubes, when local defenses are impaired ( 11 ).…”