scholarly journals Emergence of Resistance Mutations in Salmonella enterica Serovar Typhi Against Fluoroquinolones

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Takashi Matono ◽  
Masatomo Morita ◽  
Koji Yahara ◽  
Ken-ichi Lee ◽  
Hidemasa Izumiya ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Evolutionary Process ◽  
Resistance Mechanisms ◽  
Single Mutation ◽  
Nucleotide Polymorphisms ◽  
Resistance Mutations ◽  
Single Nucleotide ◽  
Salmonella Enterica Serovar Typhi ◽  
Resistant Strains ◽  
Emergence Of Resistance

Abstract Background Little is known about the evolutionary process and emergence time of resistance mutations to fluoroquinolone in Salmonella enterica serovar Typhi. Methods We analyzed S. Typhi isolates collected from returned travelers between 2001 and 2016. Based on ciprofloxacin susceptibility, isolates were categorized as highly resistant (minimum inhibitory concentration [MIC] ≥ 4 μg/mL [CIPHR]), resistant (MIC = 1–2 μg/mL [CIPR]), intermediate susceptible (MIC = 0.12–0.5 μg/mL [CIPI]), and susceptible (MIC ≤ 0.06 μg/mL [CIPS]). Results A total of 107 isolates (33 CIPHR, 14 CIPR, 30 CIPI, and 30 CIPS) were analyzed by whole-genome sequencing; 2461 single nucleotide polymorphisms (SNPs) were identified. CIPS had no mutations in the gyrA or parC genes, while each CIPI had 1 of 3 single mutations in gyrA (encoding Ser83Phe [63.3%], Ser83Tyr [33.3%], or Asp87Asn [3.3%]). CIPHR had the same 3 mutations: 2 SNPs in gyrA (encoding Ser83Phe and Asp87Asn) and a third in parC (encoding Ser80Ile). CIPHR shared a common ancestor with CIPR and CIPI isolates harboring a single mutation in gyrA encoding Ser83Phe, suggesting that CIPHR emerged 16 to 23 years ago. Conclusions Three SNPs—2 in gyrA and 1 in parC—are present in S. Typhi strains highly resistant to fluoroquinolone, which were found to have evolved in 1993–2000, approximately 10 years after the beginning of the ciprofloxacin era. Highly resistant strains with survival advantages arose from strains harboring a single mutation in gyrA encoding Ser83Phe. Judicious use of fluoroquinolones is warranted to prevent acceleration of such resistance mechanisms in the future.

scholarly journals Draft Genome Sequences of Two Extensively Drug-Resistant Strains ofMycobacterium tuberculosisBelonging to the Euro-American S Lineage

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Lesibana A. Malinga ◽  
Thomas Abeel ◽  
Christopher A. Desjardins ◽  
Talent C. Dlamini ◽  
Gail Cassell ◽  
...  
Keyword(s):  
Draft Genome ◽  
Drug Efflux ◽  
Drug Resistant ◽  
Nucleotide Polymorphisms ◽  
Genome Sequences ◽  
Single Nucleotide ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

We report the whole-genome sequencing of two extensively drug-resistant tuberculosis strains belonging to the Euro-American S lineage. The RSA 114 strain showed single-nucleotide polymorphisms predicted to have drug efflux activity.

scholarly journals Typhoid Fever due to Extended Spectrum β-Lactamase-Producing Salmonella enterica Serovar Typhi: A Case Report and Literature Review

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Abdul Azeez Ahamed Riyaaz ◽  
Vindya Perera ◽  
Sabaratnam Sivakumaran ◽  
Nelun de Silva
Keyword(s):  
Case Report ◽  
Sri Lanka ◽  
Typhoid Fever ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhi ◽  
Extended Spectrum ◽  
Cephalosporin Resistance ◽  
Resistant Strains ◽  
Derivatives Of

Emergence of cephalosporin-resistant strains of Salmonella enterica serovar Typhi is a cause of concern in the management of enteric fever. Cephalosporin resistance in Salmonella species is mainly due to the production of extended-spectrum β-lactamases (ESBLs). The majority of ESBLs in Salmonella enterica serovar Typhi are derivatives of the TEM, SHV, and CTX-M β-lactamase families. Of these, CTX-M appears to be predominant. This paper discusses the detection and molecular characterization of an ESBL-producing Salmonella enterica serovar Typhi strain isolated from a patient who was admitted to a private hospital in Sri Lanka. The three main types of β-lactamases such as TEM, SHV, and CTX-M were identified in this isolate. This case report from Sri Lanka contributes to the knowledge of the increasingly reported cases of typhoid fever due to Salmonella enterica serovar Typhi resistant to β-lactamase by ESBL production.

scholarly journals DNA Sequence Analysis of DNA Gyrase and DNA Topoisomerase IV Quinolone Resistance-Determining Regions of Salmonella enterica Serovar Typhi and Serovar Paratyphi A

2002 ◽  
Vol 46 (10) ◽  
pp. 3249-3252 ◽  
Author(s):  
Kenji Hirose ◽  
Ai Hashimoto ◽  
Kazumichi Tamura ◽  
Yoshiaki Kawamura ◽  
Takayuki Ezaki ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Dna Sequence ◽  
Salmonella Enterica ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
Single Mutation ◽  
Topoisomerase Iv ◽  
Dna Topoisomerase ◽  
Salmonella Enterica Serovar Typhi

ABSTRACT The mutations that are responsible for fluoroquinolone resistance in the gyrA, gyrB, parC, and parE genes of Salmonella enterica serovar Typhi and serovar Paratyphi A were investigated. The sequences of the quinolone resistance-determining region of the gyrA gene in clinical isolates which showed decreased susceptibilities to fluoroquinolones had a single mutation at either the Ser-83 or the Asp-87 codon, and no mutations were found in the gyrB, parC, and parE genes.

Salmonella enterica serovar Typhi in Japan, 2001–2006: emergence of high-level fluoroquinolone-resistant strains

2009 ◽  
Vol 138 (3) ◽  
pp. 318-321 ◽  
Author(s):  
M. MORITA ◽  
K. HIROSE ◽  
N. TAKAI ◽  
J. TERAJIMA ◽  
H. WATANABE ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
South East Asia ◽  
Asian Countries ◽  
Salmonella Enterica Serovar Typhi ◽  
Phage Types ◽  
Imported Cases ◽  
Resistant Strains ◽  
High Level

SUMMARYThe phage types and antimicrobial susceptibilities of 226 isolates of Salmonella enterica serovar Typhi from imported cases in Japan between 2001 and 2006 were investigated. Most (93·8%) had travelled to Asian countries, particularly South East Asia. Twenty-one phage types were identified with E1 (30·5%), UVS (15·9%) and B1 (9·3%) being the most common. The frequency of multidrug-resistant strains reached 37·0% in 2006 with phage types E1 and E9 predominating. Almost half (48·2%) of the isolates were resistant to nalidixic acid and two isolates displayed high-level fluoroquinolone resistance. Three mutations, two in gyrA and one in parC, were identified in both isolates.

scholarly journals Linked mutations at adjacent nucleotides have shaped human population differentiation and protein evolution

2018 ◽  
Author(s):  
James G. D. Prendergast ◽  
Carys Pugh ◽  
Sarah E. Harris ◽  
David A. Hume ◽  
Ian J. Deary ◽  
...  
Keyword(s):  
Human Population ◽  
Single Mutation ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mutational Spectra ◽  
Coding Regions ◽  
Selective Pressures ◽  
Distinct Process ◽  
Order Of Magnitude ◽  
Mutational Processes

AbstractDespite the fundamental importance of single nucleotide polymorphisms (SNPs) to human evolution there are still large gaps in our understanding of the forces that shape their distribution across the genome. SNPs have been shown to not be distributed evenly, with directly adjacent SNPs found unusually frequently. Why this is the case is unclear. We illustrate how neighbouring SNPs that can’t be explained by a single mutation event (that we term here sequential dinucleotide mutations, SDMs) are driven by distinct mutational processes and selective pressures to SNPs and multinucleotide polymorphisms (MNPs). By studying variation across multiple populations, including a novel cohort of 1,358 Scottish genomes, we show that, SDMs are over twice as common as MNPs and like SNPs, display distinct mutational spectra across populations. These biases are though not only different to those observed among SNPs and MNPs, but also more divergent between human population groups. We show that the changes that make up SDMs are not independent, and identify a distinct mutational profile, CA → CG → TG, that is observed an order of magnitude more often than other SDMs, including others that involve the gain and subsequent deamination of CpG sites. This suggests these specific changes are driven by a distinct process. In coding regions particular SDMs are favoured, and especially those that lead to the creation of single codon amino acids. Intriguingly selection has favoured particular pathways through the amino acid code, with epistatic selection appearing to have disfavoured sequential non-synonymous changes.

scholarly journals The Medical Triazole Voriconazole Can Select for Tandem Repeat Variations in Azole-Resistant Aspergillus Fumigatus Harboring TR34/L98H Via Asexual Reproduction

2020 ◽  
Vol 6 (4) ◽  
pp. 277
Author(s):  
Jianhua Zhang ◽  
Jan Zoll ◽  
Tobias Engel ◽  
Joost van den Heuvel ◽  
Paul E. Verweij ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Asexual Reproduction ◽  
Tandem Repeat ◽  
Experimental Evolution ◽  
High Frequency ◽  
Nucleotide Polymorphisms ◽  
Resistance Mutations ◽  
Single Nucleotide ◽  
Resistant Phenotype ◽  
Selection Of

Azole-resistant Aspergillus fumigatus isolates recovered at high frequency from patients, harbor mutations that are associated with variation of promoter length in the cyp51A gene. Following the discovery of the TR34/L98H genotype, new variations in tandem repeat (TR) length and number of repeats were identified, as well as additional single nucleotide polymorphisms (SNPs) in the cyp51A gene, indicating that the diversity of resistance mutations in A. fumigatus is likely to continue to increase. Investigating the development routes of TR variants is critical to be able to design preventive interventions. In this study, we tested the potential effects of azole exposure on the selection of TR variations, while allowing haploid A. fumigatus to undergo asexual reproduction. Through experimental evolution involving voriconazole (VOR) exposure, an isolate harboring TR343/L98H evolved from a clinical TR34/L98H ancestor isolate, confirmed by whole genome sequencing. TR343/L98H was associated with increased cyp51A expression and high VOR and posaconazole MICs, although additional acquired SNPs could also have contributed to the highly azole-resistant phenotype. Exposure to medical azoles was found to select for TR343, thus supporting the possibility of in-host selection of TR34 variants.

scholarly journals Analyses of Five Gallinacin Genes and the Salmonella enterica Serovar Enteritidis Response in Poultry

2006 ◽  
Vol 74 (6) ◽  
pp. 3375-3380 ◽  
Author(s):  
Jason R. Hasenstein ◽  
Guolong Zhang ◽  
Susan J. Lamont
Keyword(s):  
Salmonella Enterica ◽  
Bacterial Colonization ◽  
Animal Health ◽  
Nucleotide Polymorphisms ◽  
Salmonella Enterica Serovar Enteritidis ◽  
Single Nucleotide ◽  
Beta Defensins ◽  
Antibody Levels ◽  
Per Gene ◽  
Circulating Antibody

ABSTRACTGallinacins in poultry are functional equivalents of mammalian beta-defensins, which constitute an integral component of the innate immune system.Salmonella entericaserovar Enteritidis is a gram-negative bacterium that negatively affects both human and animal health. To analyze the association of genetic variations of the gallinacin genes with the phenotypic response toS. entericaserovar Enteritidis, an F1population of chickens was created by crossing four outbred broiler sires to dams of two highly inbred lines. The F1chicks were evaluated for bacterial colonization after pathogenicS. entericaserovar Enteritidis inoculation and for circulating antibody levels after inoculation withS. entericaserovar Enteritidis bacterin vaccine. Five candidate genes were studied, including gallinacins 2, 3, 4, 5, and 7. Gene fragments were sequenced from the founder individuals of the resource population, and a mean of 13.2 single-nucleotide polymorphisms (SNP) per kilobase was identified. One allele-defining SNP per gene was utilized to test for statistical associations of sire alleles with progeny response toS. entericaserovar Enteritidis. Among the five gallinacin genes evaluated, theGal3andGal7SNPs in broiler sires were found to be associated with antibody production afterS. entericaserovar Enteritidis vaccination. Utilization of these SNPs as molecular markers for the response toS. entericaserovar Enteritidis may result in the enhancement of the immune response in poultry.

scholarly journals Polyclonal pathogen populations accelerate the evolution of antibiotic resistance in patients

2021 ◽  
Author(s):  
Julio Diaz Caballero ◽  
Rachel M. Wheatley ◽  
Natalia Kapel ◽  
Carla López-Causapé ◽  
Thomas Van der Schalk ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
De Novo ◽  
Opportunistic Pathogen ◽  
Response To Treatment ◽  
Resistance Mutations ◽  
Trade Offs ◽  
Resistant Strains ◽  
Selection For ◽  
Pathogen Populations ◽  
Emergence Of Resistance

AbstractAntibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection for de novo variants. Here we show that pulmonary populations of the opportunistic pathogen P. aeruginosa are often polyclonal. Crucially, resistance evolves rapidly in patients colonized by polyclonal populations through selection for pre-existing resistant strains. In contrast, resistance evolves sporadically in patients colonized by monoclonal populations due to selection for novel resistance mutations. However, strong trade-offs between resistance and fitness occur in polyclonal populations that can drive the loss of resistant strains. In summary, we show that the within-host diversity of pathogen populations plays a key role in shaping the emergence of resistance in response to treatment.One sentence summaryAntibiotic resistance evolves quickly in patients colonized by polyclonal pathogen populations.

scholarly journals Heterogeneous Streptomycin Resistance Level Among Mycobacterium tuberculosis Strains From the Same Transmission Cluster

2021 ◽  
Vol 12 ◽  
Author(s):  
Deisy M. G. C. Rocha ◽  
Carlos Magalhães ◽  
Baltazar Cá ◽  
Angelica Ramos ◽  
Teresa Carvalho ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mycobacterium Tuberculosis ◽  
Culture Media ◽  
Streptomycin Resistance ◽  
Fitness Cost ◽  
Mouse Bone Marrow ◽  
Nucleotide Polymorphisms ◽  
Resistance Mutations ◽  
Resistance Level ◽  
Single Nucleotide

Widespread and frequent resistance to the second-line tuberculosis (TB) medicine streptomycin, suggests ongoing transmission of low fitness cost streptomycin resistance mutations. To investigate this hypothesis, we studied a cohort of 681 individuals from a TB epidemic in Portugal. Whole-genome sequencing (WGS) analyses were combined with phenotypic growth studies in culture media and in mouse bone marrow derived macrophages. Streptomycin resistance was the most frequent resistance in the cohort accounting for 82.7% (n = 67) of the resistant Mycobacterium tuberculosis isolates. WGS of 149 clinical isolates identified 13 transmission clusters, including three clusters containing only streptomycin resistant isolates. The biggest cluster was formed by eight streptomycin resistant isolates with a maximum of five pairwise single nucleotide polymorphisms of difference. Interestingly, despite their genetic similarity, these isolates displayed different resistance levels to streptomycin, as measured both in culture media and in infected mouse bone marrow derived macrophages. The genetic bases underlying this phenotype are a combination of mutations in gid and other genes. This study suggests that specific streptomycin resistance mutations were transmitted in the cohort, with the resistant isolates evolving at the cluster level to allow low-to-high streptomycin resistance levels without a significative fitness cost. This is relevant not only to better understand transmission of streptomycin resistance in a clinical setting dominated by Lineage 4 M. tuberculosis infections, but mainly because it opens new prospects for the investigation of selection and spread of drug resistance in general.

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