title: M. tuberculosis ferritin (Rv3841): Potential involvement in Amikacin (AK) & Kanamycin (KM) resistance.
abstract: Tuberculosis is an infectious disease, caused by one of the most successful human pathogen, Mycobacterium tuberculosis. Aminoglycosides, Amikacin (AK) & Kanamycin (KM) are commonly used to treat drug resistant tuberculosis. They target the protein synthesis machinery by interacting with several steps of translation. Several explanations have been proposed to explain the mechanism of aminoglycoside resistance but still our information is inadequate. Iron storing/interacting proteins were found to be overexpressed in aminoglycosides resistant isolates. Iron assimilation and utilization in M. tuberculosis plays a crucial role in growth, virulence and latency. To establish the relationship of ferritin with AK & KM resistance ferritin (Rv3841/bfrB) was cloned, expressed and antimicrobial drug susceptibility testing (DST) was carried out. Rv3841/bfrB gene was cloned and expressed in E. coli BL21 using pQE2 expression vector. Etest results for DST against AK & KM showed that the minimum inhibitory concentration (MIC) of ferritin recombinant cells was changed. Recombinants showed two fold changes in MIC with AK and three fold with KM E-strips. Overexpression of ferritin reflect the MIC shift which might be playing a critical role in the survival of mycobacteria by inhibiting/modulating the effects of AK & KM. String analysis also suggests that ferritin interacted with few proteins which are directly and indirectly involved in M. tuberculosis growth, Iron assimilation, virulence, resistance, stresses and latency.
authors: Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282004, India.
authors: Divakar
authors: D
authors: Sharma
authors: Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282004, India.
authors: Manju
authors: M
authors: Lata
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
authors: Mohammad
authors: M
authors: Faheem
authors: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.
authors: Asad Ullah
authors: AU
authors: Khan
authors: Department of Immunology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282004, India.
authors: Beenu
authors: B
authors: Joshi
authors: Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282004, India.
authors: Krishnamurthy
authors: K
authors: Venkatesan
authors: School of Studies (SOS) Zoology, Jiwaji University, Gwalior, India.
authors: Sangeeta
authors: S
authors: Shukla
authors: Department of Biochemistry, National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282004, India. Electronic address: abd1109@rediffmail.com.
authors: Deepa
authors: D
authors: Bisht
mesh_terms: D000583:Amikacin / Q000494:pharmacology*; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial / Q000187:drug effects*; D005293:Ferritins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005798:Genes, Bacterial; D007612:Kanamycin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D010957:Plasmids / Q000302:isolation & purification; D025941:Protein Interaction Mapping; D011994:Recombinant Proteins / Q000302:isolation & purification; D015183:Restriction Mapping; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014170:Transformation, Genetic / Q000187:drug effects
chemical_list: D011994:Recombinant Proteins; D007612:Kanamycin; D000583:Amikacin; D005293:Ferritins
keywords: Amikacin; Cloning; Etest; Expression; Ferritin; Kanamycin