Molecular Characterization of Rifampicin- and Isoniazid-Resistant &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; Strains Isolated in Kazakhstan

Kozhamkulov, Ulan; Akhmetova, A.; Rakhimova, Saule; Белова, Е. В.; Alenova, Arike; Bismilda, Venera; Chingissova, Lyailya; Ismailov, Shahimurat; Ramanculov, Erlan; Momynaliev, Kuvat

doi:10.7883/yoken.64.253

Cited by 32 publications

(11 citation statements)

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“…This endorsed an earlier report that codon 450 (531 in the E. coli numbering system) is the most frequently mutated in the rpoB gene. 28 However, the frequency of S450L mutation can be different in various settings around the world, such as, Kazakhstan (80.9%), 29 Bangladesh (69.4%), 22 Taiwan (66.7%), 30 China (60.9%), 31 India (57.81%), 32 South Africa (56%), 33 South Korea (53.1%), 24 Brazil (52.4%), 34 Russia (47%) 35 and Vietnam (37.8%). 26 Besides, the next most abundant RRDR mutations occurred in the present study at codons positions 430 (13/146; 8.90%), 435 (31/146; 21.23%), and 445 (47/146; 32.19%) respectively in RIF R strains.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Genetic Variants Associated with Rifampicin Resistance Level in Mycobacterium tuberculosis Clinical Isolates Collected in Guangzhou Chest Hospital, China

Hameed¹,

Fang²,

Li³

et al. 2022

IDR

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Rifampicin (RIF)-resistance, a surrogate marker for multidrug-resistant tuberculosis (TB), is mediated by mutations in the rpoB gene. We aimed to investigate the prevalence of mutations pattern in the entire rpoB gene of Mycobacterium tuberculosis clinical isolates and their association with resistance level to RIF. Methods: Among 465 clinical isolates collected from the Guangzhou Chest Hospital, drug-susceptibility of 175 confirmed Mtb strains was performed via the proportion method and Bactec MGIT 960 system. GeneXpert MTB/RIF and sanger sequencing facilitated in genetic characterization, whereas the MICs of RIF were determined by Alamar blue assay. Results: We found 150/175 (85.71%) RIF-resistant strains (MIC: 4 to >64 µg/mL) of which 57 were MDR and 81 pre-XDR TB. Genetic analysis identified 17 types of mutations 146/150 (97.33%) within RRDR (codons 426-452) of rpoB, mainly at L430 (P), D435 (V, E, G, N), H445 (N, D, Y, R, L), S450 (L, F) and L452 (P). D435V 12/146 (8.2%), H445N 16/146 (10.9%), and S450L 70/146 (47.94%) were the most frequently encountered mutations. Mutations Q432K, M434V, and N437D are rarely identified in RRDR. Deletions at (1284-1289 CCAGCT), (1295( -1303, and insertion at (1300-1302 TTC) were detected within RRDR of three RIF R strains for the first time. We detected 47 types of mutations and insertions/deletions (indels) outside the RRDR. Four RIF R strains were detected with only novel mutations/indels outside the RRDR. Two of the four had (K274Q + C897 del + I491M) and (A286V + L494P), respectively. The other two had (G1687del + P454L) and (TT1835-6 ins + I491L) individually. Compared with phenotypic characterization, diagnostic sensitivities of GeneXpert MTB/RIF and sequencing analysis were 95.33% (143/150), and 100% (150/150) respectively.

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Section: Discussionmentioning

confidence: 99%

Characterization of Genetic Variants Associated with Rifampicin Resistance Level in Mycobacterium tuberculosis Clinical Isolates Collected in Guangzhou Chest Hospital, China

Hameed¹,

Fang²,

Li³

et al. 2022

IDR

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“… 44 Another study proved that the enhancement of genes expression related to intracellular metabolic bacteria coped with Cd stress. 45 …”

Section: Resultsmentioning

confidence: 99%

“…44 Another study proved that the enhancement of genes expression related to intracellular metabolic bacteria coped with Cd stress. 45 These major up-regulated genes related to metabolism, transcription, translation, and cellular processes are shown in Table S3. † Among these genes, rpoA and rpoC related to transcription were both up-regulated.…”

Section: Resistant Phenotypic Change Of Bacteria Exposed To 2d-bp Nan...mentioning

confidence: 99%

“…In addition, under external stimuli including manganese stress, dehydration stress, and high salinity, the expressions of atpD and atpG genes in bacteria were also positively regulated. [43][44][45][49][50][51] The up-regulated mglB and rbsB genes related to the ABC operator were enriched to the bacterial chemotaxis pathway (Fig. 7 and Table S4 †).…”

Section: Resistant Phenotypic Change Of Bacteria Exposed To 2d-bp Nan...mentioning

confidence: 99%

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Development of bacterial resistance induced by low concentration of two-dimensional black phosphorus via mutagenesis

et al. 2022

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“…INH must be activated by Mtb catalase-peroxidase (KatG). − Most clinically relevant INH-resistant Mtb strains involve mutations in or deletions of katG , which abrogate activation of the INH prodrug. , In some areas, 70% of MDR-TB strains have mutations in katG , as do 100% of sequenced XDR-TB strains. , Although katG mutations are generally responsible for high-level resistance to INH in clinical isolates, those mutations can be enhanced by additional mutations in the promoter region of inhA , which cause low-level INH resistance by increasing the amount of InhA produced , and are found in up to 28% of INH-resistant clinical isolates (depending on the location of the study). − KatG activates INH to enable the formation of a covalent adduct with NAD + or NADH . As has been previously demonstrated, novel InhA inhibitors that do not require prior activation by KatG are not vulnerable to this key mechanism of INH resistance. , …”

Section: Introductionmentioning

confidence: 99%

A Virtual Screen Discovers Novel, Fragment-Sized Inhibitors ofMycobacterium tuberculosisInhA

Perryman

Wang

et al. 2015

J. Chem. Inf. Model.

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Isoniazid (INH) is usually administered to treat latent Mycobacterium tuberculosis (Mtb) infections, and is used in combination therapy to treat active tuberculosis disease (TB). Unfortunately, resistance to this drug is hampering its clinical effectiveness. INH is a prodrug that must be activated by Mtb catalase peroxidase (KatG) before it can inhibit InhA (Mtb enoyl-acyl-carrier-protein reductase). Isoniazid-resistant cases of TB found in clinical settings usually involve mutations in or deletion of katG, which abrogate INH activation. Compounds that inhibit InhA without requiring prior activation by KatG would not be affected by this resistance mechanism and hence would display continued potency against these drug-resistant isolates of Mtb. Virtual screening experiments versus InhA in the GO Fight Against Malaria project (GO FAM) were designed to discover new scaffolds that display base stacking interactions with the NAD cofactor. GO FAM experiments included targets from other pathogens, including Mtb, when they had structural similarity to a malaria target. Eight of the sixteen soluble compounds identified by docking against InhA plus visual inspection were modest inhibitors and did not require prior activation by KatG. The best two inhibitors discovered are both fragment-sized compounds and displayed Ki values of 54 and 59 μM, respectively. Importantly, the novel inhibitors discovered have low structural similarity to known InhA inhibitors and, thus, help expand the number of chemotypes on which future medicinal chemistry efforts can be focused. These new fragment hits could eventually help advance the fight against INH-resistant Mtb strains, which pose a significant global health threat.

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Molecular Characterization of Rifampicin- and Isoniazid-Resistant <i>Mycobacterium tuberculosis</i> Strains Isolated in Kazakhstan

Cited by 32 publications

References 0 publications

Characterization of Genetic Variants Associated with Rifampicin Resistance Level in Mycobacterium tuberculosis Clinical Isolates Collected in Guangzhou Chest Hospital, China

Characterization of Genetic Variants Associated with Rifampicin Resistance Level in Mycobacterium tuberculosis Clinical Isolates Collected in Guangzhou Chest Hospital, China

Development of bacterial resistance induced by low concentration of two-dimensional black phosphorus via mutagenesis

A Virtual Screen Discovers Novel, Fragment-Sized Inhibitors ofMycobacterium tuberculosisInhA

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