scholarly journals Whole-genome comparative analysis at the lineage/sublineage level discloses relationships between Mycobacterium tuberculosis genotype and clinical phenotype

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12128
Author(s):  
Andrea Monserrat Negrete-Paz ◽  
Gerardo Vázquez-Marrufo ◽  
Ma. Soledad Vázquez-Garcidueñas
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Clinical Phenotype ◽  
Effective Strain ◽  
Pulmonary Involvement ◽  
Multidrug Resistant ◽  
Nucleotide Polymorphisms ◽  
Mtbc Strain ◽  
Resistant Strains ◽  
Phylogenetic Lineages

Background Human tuberculosis (TB) caused by members of the Mycobacterium tuberculosis complex (MTBC) is the main cause of death among infectious diseases worldwide. Pulmonary TB (PTB) is the most common clinical phenotype of the disease, but some patients develop an extrapulmonary (EPTB) phenotype in which any organ or tissue can be affected. MTBC species include nine phylogenetic lineages, with some appearing globally and others being geographically restricted. EPTB can or not have pulmonary involvement, challenging its diagnosis when lungs are not implicated, thus causing an inadequate treatment. Finding evidence of a specific M. tuberculosis genetic background associated with EPTB is epidemiologically relevant due to the virulent and multidrug-resistant strains isolated from such cases. Until now, the studies conducted to establish associations between M. tuberculosis lineages and PTB/EPTB phenotypes have shown inconsistent results, which are attributed to the strain predominance from specific M. tuberculosis lineages/sublineages in the samples analyzed and the use of low-resolution phylogenetic tools that have impaired sublineage discrimination abilities. The present work elucidates the relationships between the MTBC strain lineages/sublineages and the clinical phenotypes of the disease as well as the antibiotic resistance of the strains. Methods To avoid biases, we retrieved the raw genomic reads (RGRs) of all (n = 245) the M. tuberculosis strains worldwide causing EPTB available in databases and an equally representative sample of the RGRs (n = 245) of PTB strains. A multiple alignment was constructed, and a robust maximum likelihood phylogeny based on single-nucleotide polymorphisms was generated, allowing effective strain lineage/sublineage assignment. Results A significant Odds Ratio (OR range: 1.8–8.1) association was found between EPTB and the 1.1.1, 1.2.1, 4.1.2.1 and ancestral Beijing sublineages. Additionally, a significant association between PTB with 4.3.1, 4.3.3, and 4.5 and Asian African 2 and Europe/Russia B0/W148 modern Beijing sublineages was found. We also observed a significant association of Lineage 3 strains with multidrug resistance (OR 3.8; 95% CI [1.1–13.6]), as well as between modern Beijing sublineages and antibiotic resistance (OR 4.3; 3.8–8.6). In this work, it was found that intralineage diversity can drive differences in the immune response that triggers the PTB/EPTB phenotype.

scholarly journals Thr202Ala in thyA Is a Marker for the Latin American Mediterranean Lineage of the Mycobacterium tuberculosis Complex Rather than Para-Aminosalicylic Acid Resistance

2010 ◽  
Vol 54 (11) ◽  
pp. 4794-4798 ◽  
Author(s):  
Silke Feuerriegel ◽  
Claudio Köser ◽  
Leona Trübe ◽  
John Archer ◽  
Sabine Rüsch Gerdes ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Latin American ◽  
Acid Resistance ◽  
Multidrug Resistant ◽  
Nucleotide Polymorphisms ◽  
Aminosalicylic Acid ◽  
Phenotypic Resistance ◽  
Clear Cut ◽  
Development Of Resistance ◽  
Phylogenetic Lineages

ABSTRACT Single nucleotide polymorphisms (SNPs) involved in the development of resistance represent powerful markers for the rapid detection of first- and second-line resistance in clinical Mycobacterium tuberculosis complex (MTBC) isolates. However, the association between particular mutations and phenotypic resistance is not always clear-cut, and phylogenetic SNPs have been misclassified as resistance markers in the past. In the present study, we investigated the utility of a specific polymorphism in thyA (Thr202Ala) as a marker for resistance to para-aminosalicyclic acid (PAS). Sixty-three PAS-susceptible MTBC strains comprising all major phylogenetic lineages, reference strain H37Rv, and 135 multidrug-resistant (MDR) strains from Germany (comprising 8 PAS-resistant isolates) were investigated for the presence of Thr202Ala. In both strain collections, the Thr202Ala SNP was found exclusively in strains of the Latin American Mediterranean (LAM) lineage irrespective of PAS resistance. Furthermore, PAS MICs (0.5 mg/liter) for selected LAM strains (all containing the SNP) and non-LAM strains (not containing the SNP), as well as the results of growth curve analyses performed in liquid 7H9 medium in the presence of increasing PAS concentrations (0 to 2.0 mg/liter), were identical. In conclusion, our data demonstrate that the Thr202Ala polymorphism in thyA is not a valid marker for PAS resistance but, instead, represents a phylogenetic marker for the LAM lineage of the M. tuberculosis complex. These findings challenge some of the previous understanding of PAS resistance and, as a consequence, warrant further in-depth investigations of the genetic variation in PAS-resistant clinical isolates and spontaneous mutants.

scholarly journals Pheromone killing of multidrug-resistantEnterococcus faecalisV583 by native commensal strains

2015 ◽  
Vol 112 (23) ◽  
pp. 7273-7278 ◽  
Author(s):  
Michael S. Gilmore ◽  
Marcus Rauch ◽  
Matthew M. Ramsey ◽  
Paul R. Himes ◽  
Sriram Varahan ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Cross Talk ◽  
Metabolic Pathways ◽  
Multidrug Resistant ◽  
Mobile Elements ◽  
Competitive Growth ◽  
Gi Tract ◽  
Subsequent Infection ◽  
Native Flora ◽  
Resistant Strains

Multidrug-resistantEnterococcus faecalispossess numerous mobile elements that encode virulence and antibiotic resistance traits as well as new metabolic pathways, often constituting over one-quarter of the genome. It was of interest to determine how this large accretion of mobile elements affects competitive growth in the gastrointestinal (GI) tract consortium. We unexpectedly observed that the prototype clinical isolate strain V583 was actively killed by GI tract flora, whereas commensal enterococci flourished. It was found that killing of V583 resulted from lethal cross-talk between accumulated mobile elements and that this cross-talk was induced by a heptapeptide pheromone produced by nativeE. faecalispresent in the fecal consortium. These results highlight two important aspects of the evolution of multidrug-resistant enterococci: (i) the accretion of mobile elements inE. faecalisV583 renders it incompatible with commensal strains, and (ii) because of this incompatibility, multidrug-resistant strains sharing features found in V583 cannot coexist with commensal strains. The accumulation of mobile elements in hospital isolates of enterococci can include those that are inherently incompatible with native flora, highlighting the importance of maintaining commensal populations as means of preventing colonization and subsequent infection by multidrug-resistant strains.

scholarly journals Constraints of Drug Resistance in Mycobacterium tuberculosis - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics

2017 ◽  
Vol 8 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Aleksandr I. Ilin ◽  
Murat E. Kulmanov ◽  
Ilya S. Korotetskiy ◽  
Marina V. Lankina ◽  
Gulshara K. Akhmetova ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Genetic Heterogeneity ◽  
Multidrug Resistant ◽  
Resistance Mutations ◽  
General Increase ◽  
Drug Induced ◽  
Mdr Tb ◽  
Resistant Strains

Emergence of multidrug resistant strains ofMycobacterium tuberculosis(MDR-TB) threatens humanity. This problem was complicated by the crisis in development of new anti-tuberculosis antibiotics. Induced reversion of drug resistance seems promising to overcome the problem. Successful clinical trial of a new anti-tuberculosis nanomolecular complex FS-1 has demonstrated prospectively of this approach in combating MDR-TB. Several clinical MDR-TB cultures were isolated from sputum samples prior and in the process of the clinical trial. Every isolate was tested for susceptibility to antibiotics and then they were sequenced for comparative genomics. It was found that the treatment with FS-1 caused an increase in the number of antibiotic susceptible strains among Mtb isolates that was associated with a general increase of genetic heterogeneity of the isolates. Observed impairing of phthiocerol dimycocerosate biosynthesis by disruptive mutations inppsACDsubunits indicated a possible virulence remission for the sake of persistence. It was hypothesized that the FS-1 treatment eradicated the most drug resistant Mtb variants from the population by aggravating the fitness cost of drug resistance mutations. Analysis of distribution of these mutations in the global Mtb population revealed that many of them were incompatible with each other and dependent on allelic states of many other polymorphic loci. The latter discovery may explain the negative correlation between the genetic heterogeneity of the population and the level of drug tolerance. To the best of our knowledge, this work was the first experimental confirmation of the drug induced antibiotic resistance reversion by the induced synergy mechanism that previously was predicted theoretically.

scholarly journals Antibiotic Resistance and Virulence Gene Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolated from Healthy Edible Marine Fish

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Justine Fri ◽  
Henry A. Njom ◽  
Collins N. Ateba ◽  
Roland N. Ndip
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Marine Fish ◽  
Control Strategies ◽  
Virulence Gene ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Vancomycin Mics ◽  
Resistant Strains ◽  
Mrsa Strains

Thirty-three (33) isolates of methicillin-resistant Staphylococcus aureus (MRSA) from healthy edible marine fish harvested from two aquaculture settings and the Kariega estuary, South Africa, were characterised in this study. The phenotypic antimicrobial susceptibility profiles to 13 antibiotics were determined, and their antibiotic resistance determinants were assessed. A multiplex PCR was used to determine the epidemiological groups based on the type of SCCmec carriage followed by the detection of staphylococcal enterotoxin-encoding genes sea-sed and the Panton Valentine leucocidin gene (pvl). A high antibiotic resistance percentage (67–81%) was observed for Erythromycin, Ampicillin, Rifampicin, and Clindamycin, while maximum susceptibility to Chloramphenicol (100%), Imipenem (100%), and Ciprofloxacin (94%) was recorded. Nineteen (58%) of the MRSA strains had Vancomycin MICs of ≤2 μg/mL, 4 (12%) with MICs ranging from 4–8 μg/mL, and 10 (30%) with values ≥16 μg/mL. Overall, 27 (82%) isolates were multidrug-resistant (MDR) with Erythromycin-Ampicillin-Rifampicin-Clindamycin (E-AMP-RIP-CD) found to be the dominant antibiotic-resistance phenotype observed in 4 isolates. Resistance genes such as tetM, tetA, ermB, blaZ, and femA were detected in two or more resistant strains. A total of 19 (58%) MRSA strains possessed SCCmec types I, II, or III elements, characteristic of healthcare-associated MRSA (HA-MRSA), while 10 (30%) isolates displayed SCCmec type IVc, characteristic of community-associated MRSA (CA-MRSA). Six (18%) of the multidrug-resistant strains of MRSA were enterotoxigenic, harbouring the see, sea, or sec genes. A prevalence of 18% (6/33) was also recorded for the luk-PVL gene. The findings of this study showed that marine fish contained MDR-MRSA strains that harbour SCCmec types, characteristic of either HA-MRSA or CA-MRSA, but with a low prevalence of enterotoxin and pvl genes. Thus, there is a need for continuous monitoring and implementation of better control strategies within the food chain to minimise contamination of fish with MDR-MRSA and the ultimate spread of the bug.

scholarly journals Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of pncA PCR Sequencing

2019 ◽  
Vol 57 (8) ◽  
Author(s):  
Kingsley King-Gee Tam ◽  
Kenneth Siu-Sing Leung ◽  
Gilman Kit-Hang Siu ◽  
Kwok-Chiu Chang ◽  
Samson Sai-Yin Wong ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Direct Detection ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Activity Data ◽  
Content Type ◽  
Treatment Regimens ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Respiratory Specimens

ABSTRACT An in-house-developed pncA sequencing assay for analysis of pyrazinamide (PZA) resistance was evaluated using 162 archived Mycobacterium tuberculosis complex (MTBC) isolates with phenotypic PZA susceptibility profiles that were well defined by analysis of Bactec MGIT 960 PZA kit and PZase activity data. Preliminary results showed 100% concordance between pncA sequencing and phenotypic PZA drug susceptibility test (DST) results among archived isolates. Also, 637 respiratory specimens were prospectively collected, and 158 were reported as MTBC positive by the Abbott Realtime MTB assay (96.3% sensitivity [95% confidence interval {CI}: 92.2% to 98.7%]; 100% specificity [95% CI: 99.2% to 100.0%]). Genotypic and phenotypic PZA resistance profiles of these 158 MTBC-positive specimens were analyzed by pncA sequencing and Bactec MGIT 960 PZA kit, respectively. For analysis of PZA resistance, pncA sequencing detected pncA mutations in 5/5 (100%) phenotypic PZA-resistant respiratory specimens within 4 working days. No pncA mutations were detected among PZA-susceptible specimens. Combining archived isolates with prospective specimens, 27 were identified as phenotypic PZA resistant with pncA mutation. Among these 27 samples, 6/27 (22.2%) phenotypic PZA-resistant strains carried novel pncA mutations without rpsA and panD mutations. These included 5 with mutations (a deletion [Del] at 383T [Del383T], Del 380 to 390, insertion of A [A Ins] at position 127, A Ins at position 407, and G Ins at position 508) in pncA structural genes and 1 with a mutation (T-12C) at the pncA promoter region. All six of these strains had no or reduced PZase activities, indicating that the novel mutations might confer PZA resistance. Additionally, 25/27 phenotypic PZA-resistant strains were confirmed multidrug-resistant tuberculosis (MDR-TB) strains. As PZA is commonly used in MDR-TB treatment regimens, direct pncA sequencing will rapidly detect PZA resistance and facilitate judicious use of PZA in treating PZA-susceptible MDR-TB.

scholarly journals Comprehensive Genome Analysis of Carbapenem-Resistant Strains of Raoultella Species, an Emerging Multidrug-Resistant Bacterium in Hospitals

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Xiao Yu ◽  
Beiwen Zheng ◽  
Jing Zhang ◽  
Hao Xu ◽  
Tingting Xiao ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antibiotic Resistance Genes ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Control Measures ◽  
Carbapenem Resistant ◽  
Multidrug Resistant Bacterium ◽  
The World ◽  
Resistant Strains

ABSTRACT We report the characterization of six carbapenem-resistant Raoultella spp. (CRRS) in our hospital and a genomic analysis of 58 publicly available isolates. CRRS isolates are sporadically identified around the world, and different transposons carrying carbapenemases were the resistant mechanisms. Mobile genetic elements play an important role in acquiring antibiotic resistance genes from the hospital. An improved understanding of these transposon and targeted control measures will be very valuable to prevent CRRS dissemination.

scholarly journals Fluoroquinolone Resistance amongMycobacterium tuberculosisStrains from Karachi, Pakistan: Data from Community-Based Field Clinics

2010 ◽  
Vol 55 (2) ◽  
pp. 929-930 ◽  
Author(s):  
Yasraba Rafiq ◽  
Kauser Jabeen ◽  
Rumina Hasan ◽  
Sana Jafri ◽  
Rabia Laiq ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Fluoroquinolone Resistance ◽  
First Line ◽  
Sensitivity Testing ◽  
Community Based ◽  
Strain Type ◽  
Resistant Strains

ABSTRACTA fluoroquinolone (FQ) resistance rate of 5.9% is reported in 205Mycobacterium tuberculosisisolates from patients presenting to field clinics in Karachi, Pakistan (2006 to 2009). FQ resistance among multidrug-resistant (MDR) strains was 11.1% (5/45), and it was 4.9% (5/103) inM. tuberculosisstrains susceptible to all first-line agents. Spoligotyping of resistant strains did not show dominance of one strain type. Our data reflect considerable FQ-resistantM. tuberculosisisolates and the need to consider inclusion of FQ within first-line sensitivity testing in such settings.

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