Modulation of antimicrobial resistance in clinical isolates of Enterobacter aerogenes: A strategy combining antibiotics and chemosensitisers

Abstract

The main focus of this study was to evaluate the antimicrobial susceptibility profiles of a selected number of human clinical isolates of Enterobacter aerogenes and explore the effects of selected chemosensitisers on the reversal of the resistant phenotype of these isolates.Methodology: This study design was accomplished by: (i) characterising several multidrug resistant (MDR) E. aerogenes clinical isolates; (ii) evaluating the contribution of target gene mutations to the resistance phenotype focusing on fluoroquinolones and chloramphenicol only; (iii) evaluating the contribution of membrane permeability and efflux to the MDR phenotype; (iv) assessing the combined action of selected antimicrobials and chemosensitisers (to identify combinations with synergistic effects and able to reduce the MIC); (v) understand how these combinations can modulate the permeability or efflux on these isolates. Results:Resistance to ciprofloxacin couldn't be totally reversed due to pre-existing mutations in target genes. Chloramphenicol susceptibility was efficiently restored by the addition of the selected chemosensitisers. From the modulation kinetics it was clear that phenothiazines were able to increase the accumulation of the Hoescht dye.Conclusions: Modulations of permeability and efflux in the presence of chemosensitisers help us to propose more appropriate chemotherapeutic combinations that can set the model to be used in the treatment of these and other MDR-infections.

The Municipal Sewage Discharge May Impact the Dissemination of Antibiotic-Resistant Escherichia coli in an Urban Coastal Beach

“…The discrepancy in the resistance level of E. coli may be the result of the environmental heterogeneity among bathing places. Hierarchical cluster techniques have been reported to compare antibiogram profiles' similarities and the antibiotic disturbance of pathogens [27,29]. Cluster analysis of antibiogram profiles revealed the difference of resistance phenotypes between the seawater and beach sand.…”

vB-Ea-5: a lytic bacteriophage against multi-drug-resistant Enterobacter aerogenes

“…One of the serious problems in the treatment of infections is the extended range of antibiotic-resistance among bacterial strains such as multi drug resistant E. aerogenes which is a significant challenge in treatment and has been known as the fourth most regularly bacterium isolated from hospital infections ( 25 ).…”

Reversing resistance to counter antimicrobial resistance in the World Health Organisation’s critical priority of most dangerous pathogens

“…Compounds that reverse resistance (generally termed antibiotic adjuvants, resistance breakers, antibiotic potentiators or chemosensitisers) possess no or little antimicrobial activity themselves, but when co-administered with an antibiotic, they potentiate the activity of the antibiotic [21][22][23]. Most resistance breakers act by inhibiting one of the following three resistance mechanisms: (i) inhibition of the β-lactamase enzymes that inactivate β-lactam antibiotics, (ii) inhibition of antibiotic efflux pumps, (iii) acting on the bacterial OM to breach the OM permeability barrier.…”

“…Several studies have reported that targeting of OM permeability can be an effective strategy for increasing antibiotic efficacy [22,[86][87][88]. Some antibiotic screening campaigns use a TolC mutant of E. coli as absence of the OMP TolC enhances drug sensitivity [89].…”