Bifidobacterium adolescentis is intrinsically resistant to antitubercular drugs

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.

Gut microbiome dysbiosis and correlation with blood biomarkers in active-tuberculosis in endemic setting

“…Genera (a) The genera, Faecalibacterium and Eubacterium were enriched in the TB patient group. These findings are corroborated by earlier reports in the Indian sub-continenet TB patient population [ 46 ]; (b) Catenibacterium , is reported to be enriched in HIV-infected individuals [ 55 ]; (c) Bifidobacterium was enriched in the TB patient group in this study, a known opportunistic pathogen that causes bacteremia in immunocompromised patients, or those with a compromised intestinal barrier [ 56 ]. Other members of the family, Bifidobacteria , are known to carry genes capable of conferring antibiotic-resistance to anti-tubercular drugs [ 57 ]; (d) Eggerthella is an anaerobic gram-positive bacillus associated with polymicrobial intraabdominal infections [ 58 ]; (e) Catenibacterium , (f) Collinsella , and (g) Eggerthella , were found to be enriched in the gut microbiota of TB patients in this study, they are reported to be associated with rheumatoid arthritis, another inflammatory disease [ 59 , 60 ]; and (h) Burkholderia is associated with pneumonia-derived melioidosis [ 61 ].…”

Whole-Genome Sequencing for Tracing the Genetic Diversity of Brucella abortus and Brucella melitensis Isolated from Livestock in Egypt

“…This topic needs to be further addressed in larger multicentre studies. However, the identification of Bifidobacterium adolescentis rpo B conferring resistance to rifampicin may be involved in higher phenotypic resistance in these brucellae [ 57 ]. None of the proposed antimicrobial resistance genes responsible for resistance against macrolides ( erm, mef, msr ), tetracyclines ( tet genes), beta-lactams ( mec A), or trimethoprim ( flo A) in Brucella was detected [ 53 ].…”

Microbiome-immune interactions in tuberculosis

“…A longitudinal study in TB patients reported that a multi-strain probiotic formulation ( Lactobacillus acidophilus , Lactobacillus casei , Lactobacillus rhamnosus , Lactobacillus bulgaricus , Bifidobacterium breve , Bifidobacterium longum , and Streptococcus thermophilus ) combined with supplementation of vitamins B 1 , B 6 , and B 12 increased serum concentrations of IFNγ and IL-12, compared to the control group receiving only anti-TB antibiotics and vitamin B 6 [ 212 ]. Whether rational design of safe-for-human-use probiotics can include the design of strains that withstand TB antibiotic therapy as proposed recently [ 213 ] remains to be carefully evaluated.…”