Molecular characterization of Mycobacterium tuberculosis strains resistant to isoniazid

Smaoui, Salma; Siala, Mariem; Fredj, Sondess Hadj; Kammoun, S.; Marouane, Chema; Hachicha, Salma; Ghorbel, Asma; Gdoura, Radhouane; Slim, L.; Messaoud, Taieb; Messadi, F.

doi:10.1016/j.ijmyco.2016.09.070

Cited by 5 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As katG is required for the activation of INH, mutations in katG are likely to be a first step in acquiring drug resistance and most mutations leading to resistance to INH are reported to be present in katG . The substitution S315T found here is the most frequent isoniazid-resistant mutation in several studies 48–50 . This has also been reported experimentally to be sufficient alone to confer resistance to INH 51 and decrease the affinity of INH towards the protein 52 .…”

Section: Discussionsupporting

confidence: 58%

Identification and Characterization of Genetic Determinants of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis in Southern India

Munir

Kumar

Ramalingam

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Drug-resistant tuberculosis (TB), one of the leading causes of death worldwide, arises mainly from spontaneous mutations in the genome of Mycobacterium tuberculosis . There is an urgent need to understand the mechanisms by which the mutations confer resistance in order to identify new drug targets and to design new drugs. Previous studies have reported numerous mutations that confer resistance to anti-TB drugs, but there has been little systematic analysis to understand their genetic background and the potential impacts on the drug target stability and/or interactions. Here, we report the analysis of whole-genome sequence data for 98 clinical M. tuberculosis isolates from a city in southern India. The collection was screened for phenotypic resistance and sequenced to mine the genetic mutations conferring resistance to isoniazid and rifampicin. The most frequent mutation among isoniazid and rifampicin isolates was S315T in katG and S450L in rpoB respectively. The impacts of mutations on protein stability, protein-protein interactions and protein-ligand interactions were analysed using both statistical and machine-learning approaches. Drug-resistant mutations were predicted not only to target active sites in an orthosteric manner, but also to act through allosteric mechanisms arising from distant sites, sometimes at the protein-protein interface.

show abstract

Section: Discussionsupporting

confidence: 58%

Identification and Characterization of Genetic Determinants of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis in Southern India

Munir

Kumar

Ramalingam

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In our study, there were four cases of these mutations, which led to the phenotypic resistance being misjudged as susceptibility by nucleotide MALDI-TOF-MS. Similar to other studies, katG315 (86.8%, 70/91) was the most common isoniazid-resistance mutation site in this study, followed by inhA-15 (15.4%, 14/91) ( Cao et al, 2020 ;Smaoui et al, 2016 ;Vilchèze and Jacobs, 2014 ). Among the streptomycin-resistant isolates, mutations at codon 43 in rpsL were the most prevalent, but this mutation was also found in streptomycin-susceptible strains, and has been reported in other studies ( Sreevatsan et al, 1996 ;Wang et al, 2019 ;Wu et al, 2020 ).…”

Section: Discussionsupporting

confidence: 89%

Prediction of Mycobacterium tuberculosis drug resistance by nucleotide MALDI-TOF-MS

Wu¹,

Tan²,

Yang³

et al. 2022

International Journal of Infectious Diseases

View full text Add to dashboard Cite

“…1 and our mass spectrometry data indicate that this protein is retained at high levels in the VBNC state compared to the loss of other proteins. KatG is a primary peroxidase, a defense against reactive oxygen species (ROS), and apparently activates the first-line antituberculosis antibiotic isoniazid (28,53). We anticipate that KatG's retention in VBNC cells may be related to anti-ROS activity in stress survival or VBNC induction, as observed in V. vulnificus (54,55).…”

Section: Resultsmentioning

confidence: 99%

A Proteomic Signature of Dormancy in the Actinobacterium Micrococcus luteus

et al. 2017

View full text Add to dashboard Cite

Dormancy is a protective state in which diverse bacteria, including Mycobacterium tuberculosis, Staphylococcus aureus, Treponema pallidum (syphilis), and Borrelia burgdorferi (Lyme disease), curtail metabolic activity to survive external stresses, including antibiotics. Evidence suggests dormancy consists of a continuum of interrelated states, including viable but nonculturable (VBNC) and persistence states. VBNC and persistence contribute to antibiotic tolerance, reemergence from latent infections, and even quorum sensing and biofilm formation. Previous studies indicate that the protein mechanisms regulating persistence and VBNC states are not well understood. We have queried the VBNC state of Micrococcus luteus NCTC 2665 (MI-2665) by quantitative proteomics combining gel electrophoresis, high-performance liquid chromatography, and tandem mass spectrometry to elucidate some of these mechanisms. MI-2665 is a nonpathogenic actinobacterium containing a small (2.5-Mb), high-GC-content genome which exhibits a well-defined VBNC state induced by nutrient deprivation. The MI-2665 VBNC state demonstrated a loss of protein diversity accompanied by increased levels of 18 proteins that are conserved across actinobacteria, 14 of which have not been previously identified in VNBC. These proteins implicate an anaplerotic strategy in the transition to VBNC, including changes in the glyoxylate shunt, redox and amino acid metabolism, and ribosomal regulatory processes. Our data suggest that MI-2665 is a viable model for dissecting the protein mechanisms underlying the VBNC stress response and provide the first protein-level signature of this state. We expect that this protein signature will enable future studies deciphering the protein mechanisms of dormancy and identify novel therapeutic strategies effective against antibiotictolerant bacterial infections.IMPORTANCE Dormancy is a protective state enabling bacteria to survive antibiotics, starvation, and the immune system. Dormancy is comprised of different states, including persistent and viable but nonculturable (VBNC) states that contribute to the spread of bacterial infections. Therefore, it is imperative to identify how bacteria utilize these different dormancy states to survive antibiotic treatment. The objective of our research is to eliminate dormancy as a route to antibiotic tolerance by understanding the proteins that control dormancy in Micrococcus luteus NCTC 2665. This bacterium has unique advantages for studying dormancy, including a small genome and a well-defined and reproducible VBNC state. Our experiments implicate four previously identified and 14 novel proteins upregulated in VBNC that may regulate this critical survival mechanism.KEYWORDS antibiotic tolerance, proteomics, stress response, systems biology D ormancy is a remarkable stress response in which bacteria curtail metabolic activity to survive potentially fatal external stresses. Dormancy has broad implications for many pathogenic bacteria, including Mycobacterium tuberculosis, Staphylococcus ...

show abstract

Molecular characterization of Mycobacterium tuberculosis strains resistant to isoniazid

Cited by 5 publications

References 0 publications

Identification and Characterization of Genetic Determinants of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis in Southern India

Identification and Characterization of Genetic Determinants of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis in Southern India

Prediction of Mycobacterium tuberculosis drug resistance by nucleotide MALDI-TOF-MS

A Proteomic Signature of Dormancy in the Actinobacterium Micrococcus luteus

Contact Info

Product

Resources

About