Antibiotic efflux pumps in Gram-negative bacteria: the inhibitor response strategy

Antibiotic Resistance in the Environment, with Particular Reference to MRSA

“…Carbapenemlactam antibiotics enter Gram negative bacteria via a membrane protein known as a porin, resistant bacteria can lack the specific D2 porin responsible for transport and are therefore resistant (Pirnay et al, 2002). Efflux via a membrane pump is a common mechanism and is found in Gram negative and Gram positive bacteria where five different superfamilies of efflux pumps conferring antibiotic resistance have been reported (Mahamoud et al, 2007) .…”

Computational Design of Highly Selective Antimicrobial Peptides

“…Frog species are abundant sources of AMPs 11,12 and Gram-negative bacterial species have more complex mechanisms for developing multiple resistance to classical antibiotics. 13 Initially, we constructed the AMPad database by connecting peptide primary and secondary membraneassociated structure with experimental MIC, HC 50 , and TI values and used data-mining procedures for statistical analysis of nonhomologous peptides from the database and identification of descriptors capable of distinguishing highly selective from mediocre peptide antibiotics. The rationale for this work and our second goal was to then prove the utility of selected descriptors and data mining procedures through computational "ab initio" design of highly selective peptide antibiotics with little identity to any known natural or synthetic AMP.…”

Pseudomonas aeruginosa PAO1 Resistance to Zinc Pyrithione: Phenotypic Changes Suggest the Involvement of Efflux Pumps

“…The inhibition of the efflux pump by the PMF blocker CCCP indicates that it belongs to an H ? antiporter superfamily [17]. This pump may be responsible for the cross resistance exhibited by the ZnPT-resistant strain toward cetrimide and sodium pyrithione [1] and chlorhexidine (results not shown).…”

“…Attacking the energy source will inhibit the efflux pump and allow the accumulation of harmful substances inside the bacteria to a toxic level that will reduce its tolerance to such substances. Efflux inhibitors are known to interfere with the energy building mechanisms of the cell, particularly affecting the energy levels of the bacterial membrane [11,17]. The effect of efflux pump inhibition could be manifested by reducing minimal inhibitory concentrations (MIC) for certain antibiotics and biocides [2,6] or increasing the intracellular accumulation of the harmful substance [5,22,23].…”

“…The effect of efflux pump inhibition could be manifested by reducing minimal inhibitory concentrations (MIC) for certain antibiotics and biocides [2,6] or increasing the intracellular accumulation of the harmful substance [5,22,23]. Carbonyl cyanide m-chlorophenylhydrazone (CCCP) is an extremely effective proton motive force (PMF) inhibitor [11,13,17]. Hence, CCCP has been used as an active efflux blocker [5,13,23].…”