Multidrug-Resistant Mycobacterium tuberculosis

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: 30 April 2024 | Viewed by 8326

Special Issue Editors


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Guest Editor
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
Interests: tuberculosis; multi drug resistance; B cells; antibodies; host-pathogen interactions; Mycobacterium tuberculosis Latency

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Guest Editor
Drug Discovery and Development Centre (H3D), University of Cape Town, Cape Town, South Africa
Interests: drug resistance; tuberculosis; drug discovery and development; Mycobacterial metabolism and physiology

Special Issue Information

Dear Colleagues,

Tuberculosis (TB) anywhere increases the risk of TB worldwide. Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that is transmitted by aerosol from infected individuals. Mtb aerosol produced by coughing or close contact with an active tuberculosis (TB) patient not only increases the risk of disease transmission, but has also been linked to several outbreak reports. Public health programs should perform core TB control activities to prevent these kinds of outbreaks in all countries, regardless of TB incidence. The diagnosis and identification of TB cases may be straightforward; however, diagnosing TB and regular TB treatment are often challenging. This could be due to the prevalence of poverty among patients, a lack of access to healthcare facilities, including delayed diagnosis, etc. Irregular TB treatment may lead to drug-resistant TB cases. The spread of drug-resistant tuberculosis can be controlled by the quick diagnosis of patients, followed by recommended treatment guidelines, and monitoring patients' responses over time.

MDR-TB is caused by Mycobacterium tuberculosis strains that acquire resistance to isoniazid (INH) and rifampicin (RIF). MDR-TB may evolve as extensively drug-resistant (XDR) TB, which is a severe form of MDR- TB. The potential transmission of drug-resistant TB is a severe public health concern. This requires enhanced efforts to diagnose and treat latent TB infection, thereby accelerating progress towards TB elimination, as well as the prevention of future cases.

Authors are invited to submit articles addressing antimicrobial resistance, the treatment and drug resistance of tuberculosis, multi-drug resistance, latent TB infection, transmission and reactivation, its mechanisms, drivers, spread, and new approaches to study, control, and overcome tuberculosis infection and disease.

Potential topics include, but are not limited to, the following:

  • Multi-drug-resistant TB;
  • Latent TB infection and TB reactivation;
  • Public health, resources, and their contribution to global TB burden;
  • Antimicrobial-resistant TB burden;
  • Mechanisms leading to antimicrobial resistance;
  • Small-molecule inhibitors of Mycobacterium tuberculosis;
  • Omics technology for antimicrobial resistance and TB surveillance;
  • Prevention of the emergence and dissemination of antimicrobial resistance;
  • MDR/XDR-TB management;
  • Antibiotics and inhibitors.

Dr. Uma Shankar Gautam
Dr. Vinayak Singh
Guest Editors

Manuscript Submission Information

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Keywords

  • multi-drug resistance TB
  • MDR/XDR-TB management
  • antibiotics and inhibitors
  • antimicrobial-resistance prevention and control

Published Papers (6 papers)

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Research

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10 pages, 557 KiB  
Article
Implementation of Whole Genome Sequencing of Tuberculosis Isolates in a Referral Center in Rome: Six Years’ Experience in Characterizing Drug-Resistant TB and Disease Transmission
by Angela Cannas, Ornella Butera, Antonio Mazzarelli, Francesco Messina, Antonella Vulcano, Mario Pasquale Parracino, Gina Gualano, Fabrizio Palmieri, Antonino Di Caro, Carla Nisii, Carla Fontana and Enrico Girardi
Antibiotics 2024, 13(2), 134; https://doi.org/10.3390/antibiotics13020134 - 30 Jan 2024
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Abstract
Over the past years, Tuberculosis (TB) control strategies have been effective in reducing drug-resistant (DR) TB globally; however, a wider implementation of new diagnostic strategies, such as Whole genome sequencing (WGS), would be critical for further improvement. The aim of this study, based [...] Read more.
Over the past years, Tuberculosis (TB) control strategies have been effective in reducing drug-resistant (DR) TB globally; however, a wider implementation of new diagnostic strategies, such as Whole genome sequencing (WGS), would be critical for further improvement. The aim of this study, based on WGS of Mycobacterium tuberculosis (MTB) strains isolated in a TB referral center over 6 years, was to evaluate the efficacy of this methodology in improving therapy guidance for clinicians and in improving the understanding of the epidemiology of TB transmission. WGS was performed in addition to pDST on 1001 strains consecutively isolated between January 2016 and December 2021; the results allowed us to improve the quality of data on resistance and to identify possible clusters of transmission. Prediction of rifampicin-resistant (RR) or multi-drug-resistant TB strains (MDR-TB, defined as resistance to at least rifampicin and isoniazid) was obtained for 50 strains (5%). Mutations predictive of an MDR isolate were further characterized, and Ser450Leu and Ser315Thr were found to be the most frequent mutations in rpoB and katG genes, respectively. Discordances between WGS and phenotypic drug susceptibility testing (pDST) were found in few strains, and their impact on clinical decisions and outcome was addressed. The introduction of WGS in our Institute improved our diagnostic routine, allowing accurate patient management, and was a valid instrument for epidemiological investigations and infection control. Full article
(This article belongs to the Special Issue Multidrug-Resistant Mycobacterium tuberculosis)
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13 pages, 296 KiB  
Article
Prevalence of Beijing Central Asian/Russian Cluster 94-32 among Multidrug-Resistant M. tuberculosis in Kazakhstan
by Ainur Akhmetova, Venera Bismilda, Lyailya Chingissova, Maxim Filipenko, Ainur Akilzhanova and Ulan Kozhamkulov
Antibiotics 2024, 13(1), 9; https://doi.org/10.3390/antibiotics13010009 - 20 Dec 2023
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Abstract
The Beijing genotype is the most distributed M. tuberculosis family in Kazakhstan. In this study, we identified dominant Beijing clusters in Kazakhstan and assessed their drug susceptibility profiles and association with the most widely spread mutation Ser531Leu of the rpoB gene and the [...] Read more.
The Beijing genotype is the most distributed M. tuberculosis family in Kazakhstan. In this study, we identified dominant Beijing clusters in Kazakhstan and assessed their drug susceptibility profiles and association with the most widely spread mutation Ser531Leu of the rpoB gene and the mutation Ser315Thr of the katG gene associated with resistance to rifampicin and isoniazid, respectively. M. tuberculosis isolates (n = 540) from new TB cases were included in the study. MIRU-VNTR genotyping was performed for 540 clinical isolates to determine M. tuberculosis families using 24 loci. RD analysis was additionally performed for the Beijing isolates. The identification of mutations in the drug-resistance genes of M. tuberculosis was performed with allele-specific real-time PCR and Sanger sequencing. The Beijing genotype was identified in 60% (324/540) of the clinical isolates. Central Asian/Russian cluster 94-32 was the most distributed cluster among the Beijing isolates (50.3%; 163/324). Three other dominant Beijing clusters were identified as 94-33 (3.4%; 11/324), 100-32 (3.1%; 10/324) and 99-32 (3.1%; 10/324). The Beijing genotype was associated with drug-resistant TB (p < 0.0001), including multidrug-resistant TB (p < 0.0001), in our study. An association of the mutation Ser531Leu of the rpoB gene with the Beijing genotype was found (p < 0.0001; OR = 16.0000; 95%CI: 4.9161–52.0740). Among the Beijing isolates, cluster 94-32 showed an association with MDR-TB (p = 0.021). This is why the evaluation of the Beijing genotype and its clusters is needed to control MDR-TB in Kazakhstan. Full article
(This article belongs to the Special Issue Multidrug-Resistant Mycobacterium tuberculosis)
15 pages, 580 KiB  
Article
Molecular Analysis of Anti-Tuberculosis Drug Resistance of Mycobacterium tuberculosis Isolated in the Republic of Korea
by Se-Mi Jeon, Sanghee Park, Na-Ra Lim, Noori Lee, Jihee Jung, Nackmoon Sung and Seonghan Kim
Antibiotics 2023, 12(8), 1324; https://doi.org/10.3390/antibiotics12081324 - 17 Aug 2023
Viewed by 1093
Abstract
Rapid and accurate detection of tuberculosis (TB) drug resistance is critical for the successful treatment and control of TB. Here, we investigated resistance to anti-TB drugs and genetic variations in 215 drug-resistant Mycobacterium tuberculosis isolates in Korea. Genetic variations were observed in rpoB [...] Read more.
Rapid and accurate detection of tuberculosis (TB) drug resistance is critical for the successful treatment and control of TB. Here, we investigated resistance to anti-TB drugs and genetic variations in 215 drug-resistant Mycobacterium tuberculosis isolates in Korea. Genetic variations were observed in rpoB Ser531Leu, katG Ser315Thr, and gyrA Asp94Gly; however, the minimum inhibitory concentrations varied, which can be attributed to other resistance mechanisms. Examination of genetic relatedness among drug-resistant isolates revealed that the cluster size of resistant bacteria was less than six strains, suggesting no evidence of a large-scale epidemic caused by a specific strain. However, rpoC mutants of the rifampicin-resistant isolates were composed of five types of clusters, suggesting that these compensatory mutations advance propagation. In the present study, more than 90% of the resistance mechanisms to major anti-TB drugs were identified, and the effect of each mutation on drug resistance was estimated. With the clinical application of recent next-generation sequencing-based susceptibility testing, the present study is expected to improve the clinical utilization of genotype-based drug susceptibility testing for the diagnosis and treatment of patients with drug-resistant TB. Full article
(This article belongs to the Special Issue Multidrug-Resistant Mycobacterium tuberculosis)
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9 pages, 2209 KiB  
Communication
Mycobacterium tuberculosis Rv0229c Shows Ribonuclease Activity and Reveals Its Corresponding Role as Toxin VapC51
by Sung-Min Kang
Antibiotics 2023, 12(5), 840; https://doi.org/10.3390/antibiotics12050840 - 01 May 2023
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Abstract
The VapBC system, which belongs to the type II toxin–antitoxin (TA) system, is the most abundant and widely studied system in Mycobacterium tuberculosis. The VapB antitoxin suppresses the activity of the VapC toxin through a stable protein–protein complex. However, under environmental stress, [...] Read more.
The VapBC system, which belongs to the type II toxin–antitoxin (TA) system, is the most abundant and widely studied system in Mycobacterium tuberculosis. The VapB antitoxin suppresses the activity of the VapC toxin through a stable protein–protein complex. However, under environmental stress, the balance between toxin and antitoxin is disrupted, leading to the release of free toxin and bacteriostatic state. This study introduces the Rv0229c, a putative VapC51 toxin, and aims to provide a better understanding of its discovered function. The structure of the Rv0229c shows a typical PIN-domain protein, exhibiting an β1-α1-α2-β2-α3-α4-β3-α5-α6-β4-α7-β5 topology. The structure-based sequence alignment showed four electronegative residues in the active site of Rv0229c, which is composed of Asp8, Glu42, Asp95, and Asp113. By comparing the active site with existing VapC proteins, we have demonstrated the justification for naming it VapC51 at the molecular level. In an in vitro ribonuclease activity assay, Rv0229c showed ribonuclease activity dependent on the concentration of metal ions such as Mg2+ and Mn2+. In addition, magnesium was found to have a greater effect on VapC51 activity than manganese. Through these structural and experimental studies, we provide evidence for the functional role of Rv0229c as a VapC51 toxin. Overall, this study aims to enhance our understanding of the VapBC system in M. tuberculosis. Full article
(This article belongs to the Special Issue Multidrug-Resistant Mycobacterium tuberculosis)
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10 pages, 376 KiB  
Article
Characteristics of Previous Tuberculosis Treatment History in Patients with Treatment Failure and the Impact on Acquired Drug-Resistant Tuberculosis
by Soedarsono Soedarsono, Ni Made Mertaniasih, Tutik Kusmiati, Ariani Permatasari, Wiwik Kurnia Ilahi and Amelia Tantri Anggraeni
Antibiotics 2023, 12(3), 598; https://doi.org/10.3390/antibiotics12030598 - 16 Mar 2023
Cited by 3 | Viewed by 1802
Abstract
Tuberculosis (TB) treatment failure is a health burden, as the patient remains a source of infection and may lead to the development of multi-drug resistance (MDR). Information from cases of treatment failure that develop into MDR, which is related to a history of [...] Read more.
Tuberculosis (TB) treatment failure is a health burden, as the patient remains a source of infection and may lead to the development of multi-drug resistance (MDR). Information from cases of treatment failure that develop into MDR, which is related to a history of previous TB treatment, in accordance with the pharmacokinetic aspect, is one important thing to prevent TB treatment failure and to prevent drug resistance. This was an observational descriptive study in an acquired MDR-TB patient who had a prior history of treatment failure. A structured questionnaire was used to collect information. The questionnaire consisted of a focus on the use of TB drug formulas during the treatment period, as well as when and how to take them. This study included 171 acquired MDR-TB patients from treatment failure cases. An amount of 64 patients received the separated TB drug, and 107 patients received the fixed dose combination (FDC) TB drug. An amount of 21 (32.8%) patients receiving separated TB drug and six (5.6%) patients receiving FDC TB drug took their drug in divided doses. In addition, three (4.7%) patients receiving separated TB drug and eight (7.5%) patients receiving FDC TB drug took their drug with food. An amount of 132 out of 171 (77.2%) patients had a history of incorrect treatment that developed into MDR-TB. Education on how to take the correct medication, both the separate version and the FDC TB drug, according to the pharmacokinetic aspect, is important before starting TB treatment. Full article
(This article belongs to the Special Issue Multidrug-Resistant Mycobacterium tuberculosis)
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Review

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17 pages, 1540 KiB  
Review
How We Treat Drug-Susceptible Pulmonary Tuberculosis: A Practical Guide for Clinicians
by Niccolò Riccardi, Sara Occhineri, Elisa Vanino, Roberta Maria Antonello, Agostina Pontarelli, Francesca Saluzzo, Tiziana Masini, Giorgio Besozzi, Marina Tadolini, Luigi Codecasa and on behalf of StopTB Italia
Antibiotics 2023, 12(12), 1733; https://doi.org/10.3390/antibiotics12121733 - 14 Dec 2023
Viewed by 1303
Abstract
Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis [...] Read more.
Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis-resistant strains. In this narrative review, through a fictional suggestive case of DS PTB, we guide the reader in a step-by-step commentary to provide an updated review of current evidence in the management of TB, from diagnosis to post-treatment follow-up. World Health Organization and Centre for Diseases Control (CDC) guidelines for TB, as well as the updated literature, were used to support this manuscript. Full article
(This article belongs to the Special Issue Multidrug-Resistant Mycobacterium tuberculosis)
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