Strategies for bypassing the membrane barrier in multidrug resistant Gram‐negative bacteria

Abstract

International audienceIn Gram-negative bacteria, the envelope is a sophisticated barrier protecting the cell against external toxic compounds. Membrane transporters, e.g., porins or efflux pumps, are main filters regulating the internal accumulation of various hydrophilic molecules. Regarding bacterial susceptibility towards antibacterial agents, membrane permeability is part of the early bacterial defense. The bacterium manages the translocation process, influx and efflux, to control the intracellular concentration of various molecules. Antibiotics and biocides are substrates of these mechanisms and the continuing emergence of multidrug resistant isolates is a growing worldwide health concern. Different strategies could be proposed to bypass the bacterial membrane barrier, comprising influx and efflux mechanisms, in order to restore the activity of antibiotics against resistant bacteria

Highly Solvent Tolerance in Serratia marcescens IBBPo15

“…Like in other Gram-negative bacteria, the envelope of S. marcescens is an important barrier that protects the cell against toxic compounds 4 . However, toxic organic solvents are able to penetrate into cytoplasmic membrane resulting in swelling of the membrane and increase of membrane fluidity which leads to the loss of membrane functionality and to the damage of bacterial cell.…”

“…Surface bacterial structures, cell wall and cytoplasmic membrane, surround each bacterial cell and create selective barriers between the cell interior and the outside of the cell 3 . They are the first site of contact between the cell and toxic compounds which are able to penetrate into cytoplasmic membrane and affect the membrane functions 3,4 . Therefore, bacteria developed adaptation mechanisms to counteract the damage originated from toxic compounds and to prevent their accumulation inside of the cell 3 .…”

“…Therefore, bacteria developed adaptation mechanisms to counteract the damage originated from toxic compounds and to prevent their accumulation inside of the cell 3 . Membrane transporters, such as porins or efflux pumps, are main filters regulating the internal accumulation of toxic compounds 4 . Porins OmpF (with molecular weight of 41 kDa) and OmpC (40 kDa) which exist in outer membrane of S. marcescens cells are two non-specific protein channels that serve to take in nutrients and toxic compounds, and export waste products 5,6 .…”

Epidihydropinidine, the main piperidine alkaloid compound of Norway spruce (Picea abies) shows promising antibacterial and anti-Candida activity

“…We suggest that ()-epidihydropinidine, as a relatively hydrophilic water soluble molecule [79], is exerting its growth inhibitory effects on P. aeruginosa, and other gram-negative bacteria, by travelling through porins, water-filled channels in the outer lipopolysaccharide membrane and reaching possible target in periplasmic space or at inner cell membrane [80].…”

Mechanisms Determining Bacterial Biofilm Resistance to Antimicrobial Factors

“…A set of efflux systems facilitates bacteria to survive in extreme environments. Bacterial efflux pumps are involved in the multidrug resistance (MDR) phenotype combined with other more specific resistance systems including target mutation and enzymatic modification of antimicrobial agents (Zgurskaya & Nikaido, 2000;Davin-Regli et al, 2008;Bolla et al, 2011). The mechanism of efflux pumps in Escherichia coli, Enterobacter aerogenes and Klebsiella pneumoniae may also serve down regulation of porin production that slow down the penetration of hydrophilic solutes, and decrease the transmembrane diffusion of lipophilic solutes (Nikaido & Vaara, 1985;Plésiat & Nikaido, 1992;Li & Nikaido, 2004;Pagés et al, 2008).…”