Efficiency of a Tetracycline-Adjuvant Combination Against Multidrug Resistant Pseudomonas aeruginosa Tunisian Clinical Isolates

Abstract

The growing number of multidrug resistant strains in Tunisia has become a serious health concern contributing to high rate of mortality and morbidity. Since current antibiotics are rapidly becoming ineffective, novel strategies to combat resistance are needed. Recently, we demonstrated that combination of a tetracycline antibiotic with various polyaminoisoprenyl adjuvants can sustain the life span and enhance the activity of these drugs against Pseudomonas aeruginosa reference strain (PA01). In the context of our continuing studies, the effective approach of antibiotic-adjuvant was investigated against a large panel of P. aeruginosa Tunisian clinical strains collected from the Military Hospital of Tunis. In this paper, we demonstrated that the combination of a farnesyl spermine compound 3 used at concentrations ranging from 2.5 to 10 µM, in the presence of doxycycline or minocycline leads to a significant decrease of P. aeruginosa antibiotic resistance.

3-Amino-Substituted Analogues of Fusidic Acid as Membrane-Active Antibacterial Compounds

“…The literature reports that simple unsubstituted polyamines, spermine and spermidine, can act synergistically with a number of antibiotics [ 60 , 61 ]. Moreover, recent studies of natural or synthetic products containing polyamines have shown that molecules, such as squalamine [ 62 ], motuporamine MOTUN44 [ 63 ], ianthelliformisamine [ 64 ], 6-bromoindolglyoxamide [ 65 ], and polyaminoisoprenoid NV716 [ 66 , 67 ], possess both an antimicrobial effect and the ability to enhance the activity of antibiotics by increasing membrane permeability and/or membrane depolarization [ 68 ].…”

An Original and Efficient Antibiotic Adjuvant Strategy to Enhance the Activity of Macrolide Antibiotics against Gram-Negative Resistant Strains

“…Gram-negative bacteria can proceed to the modification of lipid A or proteins in OM composition leading to the resistance or antibiotic susceptibility of the considered species [ 13 ]. In a previous study, we determined that the combination of a farnesyl spermine compound 3 used at concentrations ranging from 2.5 to 10 µM, in the presence of doxycycline or minocycline, leads to a significant decrease of P. aeruginosa antibiotic resistance towards these antibiotics [ 37 ]. In the context of our continuing studies, we have demonstrated a stronger synergetic effect using a combination of compound 3 and a macrolide leading to an increase in Gram-negative bacteria susceptibility to this antibiotic family.…”

“…To discover new compounds capable of perturbing the Gram-negative OM, our group has recently developed the design and use of polyaminoisoprenyl derivatives as antibiotic enhancers exhibiting a strong effect on the level of tetracycline antibiotics susceptibility against resistant P. aeruginosa bacterial strains [ 35 , 36 , 37 , 38 ]. In the continuing course of our studies, we report herein a promising strategy to combat Gram-negative resistant strains consisting of the combination of a macrolide antibiotic with polyaminoisoprenyl adjuvant derivatives leading to a significant decrease of antibiotic resistance and increase of Gram-negative strains susceptibility towards macrolides.…”

Recent Approaches for Downplaying Antibiotic Resistance: Molecular Mechanisms

“…The molecules inhibit efflux pumps by collapsing the proton-motive force (PMF) caused by the induction of inner membrane depolarization [ 108 ]. Another study investigated the combined effect of farnesyl spermine compound 3 with minocycline and doxycycline and resulted in a substantial decrease in antibiotic resistance in P. aeruginosa [ 109 ]. Sometimes, the coating of compounds can also enhance the antimicrobial activity of drugs.…”