Bifidobacterium adolescentis is intrinsically resistant to antitubercular drugs

Dhanashree Lokesh,Rajagopal Kammara,Raman Parkesh

doi:10.1038/s41598-018-30429-2

Dhanashree Lokesh, Rajagopal Kammara + Show 1 more

Open Access

https://doi.org/10.1038/s41598-018-30429-2

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Abstract

Multiple mutations in the β subunit of the RNA polymerase (rpoβ) of Mycobacterium tuberculosis (Mtb) are the primary cause of resistance to rifamycin (RIF). In the present study, bifidobacterial rpoβ sequences were analyzed to characterize the mutations that contribute to the development of intrinsic resistance to RIF, isoniazid, streptomycin and pyrazinamide. Sequence variations, which mapped to cassettes 1 and 2 of the rpoβ pocket, are also found in multidrug-resistant Mtb (MDR Mtb). Growth curves in the presence of osmolytes and different concentrations of RIF showed that the bacteria adapted rapidly by shortening the growth curve lag time. Insight into the adapted rpoβ DNA sequences revealed that B. adolescentis harbored mutations both in the RIF pocket and in regions outside the pocket. The minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) indicated that B. longum, B. adolescentis and B. animalis are resistant to antitubercular drugs. 3D-homology modeling and binding interaction studies using computational docking suggested that mutants had reduced binding affinity towards RIF. RIF-exposed/resistant bacteria exhibited variant protein profiles along with morphological differences, such as elongated and branched cells, surface conversion from rough to smooth, and formation of a concentrating ring.

Highlights

The human gut microbiome consists of a vast number of microorganisms and is considered to be a bacterial ecosystem
The European Food Safety Authority (EFSA) report on Qualified Presumption of Safety (QPS) directs that the antibiotic status of microorganisms should be determined before approval[3]
There was a difference in the resistance observed among these organisms (Fig. 1), demonstrating that bifidobacteria were more immune to drugs, such as RIF, pyrazinamide, isoniazid, and streptomycin, used in multidrug combinations (Table 1)

Summary

Introduction

The human gut microbiome consists of a vast number of microorganisms and is considered to be a bacterial ecosystem. The great trouble with the use of antibiotic-resistant probiotics is the serious chance that horizontal gene transfer among gut microbes could create harmful antibiotic-resistant bacteria. This means that antibiotic resistance per se is not considered to be a safety issue, but may be a concern if it leads to the transfer of resistance. Rough-surfaced Brucella are RIF-resistant and less virulent than RIF-sensitive strains[9,10] These observations have led to the development of stable, rough, attenuated strains for use in vaccines against brucellosis. We describe specific causes of RIF resistance in bifidobacteria and compare these microorganisms with Escherichia coli and MDR Mtb. The mechanistic aspects of Bifidobacterial resistance to RIF have not reported, and, this study is intended to be the foremost of its sort

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