Abstract
Efflux proteins are transport proteins, which are involved in transporting different substrates from the cell to the external environment, including antibiotics. The efflux mechanism and efflux pumps are a major reason underlying emerging rampant antibiotic resistance (AR) in microbes. To reduce the resources required and time of identification, characterization and classification of bacterial efflux proteins, we have developed a fast and accurate support vector machine based two-tier prediction system, BacEffluxPred, which can predict bacterial efflux proteins responsible for AR and identify their corresponding families. A leave-one-out cross-validation also called jackknife procedure was used for performance evaluation. The accuracy to discriminate bacterial AR efflux from non-AR efflux was obtained as 85.81% (at tier-I) while accuracies for prediction of efflux pump families like ABC, MFS, RND and MATE family were found 92.13%, 85.39%, 91.01% and 99.44%, respectively (at tier-II). Benchmarking on an independent dataset also showed that BacEffluxPred had comparable accuracy for prediction of bacterial AR efflux pumps and their families. This is the first in-silico tool for predicting bacterial AR efflux proteins and their families and is freely available as both web-server and standalone versions at http://proteininformatics.org/mkumar/baceffluxpred/.
Highlights
Efflux proteins are transport proteins, which are involved in transporting different substrates from the cell to the external environment, including antibiotics
In bacteria several mechanisms contribute to development of antibiotic resistance (AR) for example, (a) evolving mutations in the antibiotic targets, (b) modifications in the bacterial cell surface which prevents antibiotics from penetrating inside the cell, (c) efflux pumps which pump out the antibiotics from the cell even before they reach their target, and (d) producing enzymes which inactivate the antibiotics
On the basis of sequence conservation and functional similarities, secondary transporters are further divided into four families namely, the major facilitator superfamily (MFS)[7], the resistance-nodulation and cell division (RND) family[8], the small multidrug resistance (SMR) family[9] and the Department of Biophysics, University of Delhi South Campus, New Delhi, 110021, Delhi, India. ✉e-mail: manish@ south.du.ac.in www.nature.com/scientificreports/
Summary
Efflux proteins are transport proteins, which are involved in transporting different substrates from the cell to the external environment, including antibiotics. On the basis of sequence similarity pattern, specificity towards different substrates, number of components, number of trans-membrane spanning regions, energy sources and structural features, efflux pumps can be divided in two major families (i) primary transporters, which use ATP as the energy source, called ATP-binding cassette (ABC) transporter[6], and (ii) secondary transporters, which employ proton (or sodium) gradient as a source of energy. On the basis of sequence conservation and functional similarities, secondary transporters are further divided into four families namely, the major facilitator superfamily (MFS)[7], the resistance-nodulation and cell division (RND) family[8], the small multidrug resistance (SMR) family[9] and the Department of Biophysics, University of Delhi South Campus, New Delhi, 110021, Delhi, India. It is well established that efflux pumps have played a key role in the emergence of antibiotic resistance in several bacterial pathogens[2,11,12,13,14]
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