Abstract
Recent outbreaks of NDM-1-positive Entero-bacteriaceae in Great Britain and India and the highly pathogenic Escherichia coli strain EHEC O104:H4 in Germany and some other E.U. countries point out an urgent need for the ability to decide on appropriate antibiotics to treat multi-drug-resistant (MDR) bacteria. Here we propose a simple criterion for choosing antibiotics based on characteristics of electron donor and acceptor properties. Using molecular descriptors, such as electron-ion interaction potential (EIIP) and average quasi-valence number (AQVN), which can describe potential long-range interactions between therapeutic molecules and their targets, we have been able to suggest appropriate antibiotics for treatment of MDR bacterial infections. To demonstrate the prospective usefulness of these molecular descriptors we have used this informatics system to propose that pleuromutilins and nitrofurans could be effective against of NDM-1-positive Enterobacteriacea and that aminoglycosides, macrolides and pluromutilins (and possibly nitrofurans) could be suitable for treatment of the highly pathogenic Escherichia coli strain EHEC O104:H4. Similarly, because of their specific electronic properties, we can also suggest antibiotics that could be potentially effective against other MDR bacteria. The proposed antibiotics should be further evaluated for their treatment potentials.
Highlights
The worldwide morbidity and mortality rates attributed to multi-drug-resistant (MDR) pathogens have been increasing rapidly
In order to determine the range of molecular descriptors for each of the antibiotic classes that we analyzed, we have presented the values of electron-ion interaction potential (EIIP) and average quasivalence number (AQVN) calculated for 230 penams, cephems, carbapenems and penems, monobactams, β-lactamase inhibitors, quinolones, aminoglycosides, ansamycins, tetracyclines, macrolides, pleuromutilins, sulfonamides, rifamycins, lincosamides, glycopeptides, nitromidizoles, oxazolidinones, lipopeptides, streptogramins and nitrofurans, among other possible antibiotics (Supplementary Table 1)
We demonstrated that the specific AQVN/EIIP domains combined with the structural properties of molecules can be used as a possible filter for the virtual screening of molecular libraries for new active drug candidates[4,6,7,8]
Summary
The worldwide morbidity and mortality rates attributed to multi-drug-resistant (MDR) pathogens have been increasing rapidly. (NDM-1), was heralded as a potential major global health problem due to resistance to most if not all antibiotics[2]. E.U. countries of Enterohaemorrhagic E. coli (EHEC O104:H4) bacteria that are resistant to a broad spectrum of antibiotics, as well as cases of haemolytic uraemic syndrome (HUS), have emphasized the urgent need for effective antibiotics for treatment of severe infections caused by MDR bacteria[3]. Average quasi-valence number (AQVN)[4,5], were used for the discovery of potential new molecules with anti-HIV activities[6,7,8]. We have used these same molecular descriptors to analyze antibiotics for their potential use against MDR bacteria, such as NDM-1-positive. Based on results of this analysis, we have proposed a simple and general chemoinformatics criterion for selection of antibiotics that could be potentially effective for treatment of MDR bacteria
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
