Expression of Mycobacterium tuberculosis NLPC/p60 family protein Rv0024 induce biofilm formation and resistance against cell wall acting anti-tuberculosis drugs in Mycobacterium smegmatis
| Autor: | Avinash Padhi, Geetanjali Ganguli, Sumanta Kumar Naik, Avinash Sonawane, Srabasti Sengupta |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Tuberculosis Lipoproteins Mycobacterium smegmatis 030106 microbiology Immunology Antitubercular Agents Gene Expression Peptidoglycan Drug resistance Microbiology Bacterial Adhesion Amidohydrolases Mycobacterium tuberculosis Mice 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Microscopy Electron Transmission Drug Resistance Bacterial medicine Animals Microbial Viability Microscopy Confocal biology Isoniazid Biofilm biology.organism_classification medicine.disease Endocytosis Recombinant Proteins Infectious Diseases chemistry Biofilms Bacteria medicine.drug |
| Zdroj: | Microbes and Infection. 18:224-236 |
| ISSN: | 1286-4579 |
| DOI: | 10.1016/j.micinf.2015.11.007 |
| Popis: | Bacterial species are capable of living as biofilm and/or planktonic forms. Role of biofilms in the pathogenesis of several human pathogens is well established. However, in case of Mycobacterium tuberculosis (Mtb) infection the role of biofilms and the genetic requirements for biofilm formation remains largely unknown. We herein report that ectopic expression of Mtb Rv0024, encoding a putative peptidoglycan amidase, in non-pathogenic Mycobacterium smegmatis(Msm) strain (MsmRv0024) confer at least 10-fold increase in resistance against two prominent anti-tuberculosis drugs isoniazid and pyrazinamide. We further report that the development of resistance was due to significant increase in biofilm formation by Rv0024. Transmission electron microscopy revealed differences in cell surface architecture of MsmRv0024 when compared with Msm wild-type (WT) and vector control Msm pSMT3 (pSMT3) strains and this aggregation pattern was due to increased cell wall hydrophobicity, as determined by Bacterial adhesion to hydrocarbons assay (BATH). Confocal microscopy study showed increased adherence of MsmRv0024 bacteria to lung epithelial cells as compared to pSMT3 strain. However, infection studies showed no differences in host cell invasion and intracellular survival in mouse macrophages. We envision that Rv0024 may play a critical role in initial infection process, adherence to host cells and drug resistance. Thus, Rv0024 may be considered as a potential drug target for the treatment of tuberculosis. |
| Databáze: | OpenAIRE |
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