scholarly journals Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance

2009 ◽  
Vol 19 (7) ◽  
pp. 1214-1223 ◽  
Author(s):  
J. Feng ◽  
A. Lupien ◽  
H. Gingras ◽  
J. Wasserscheid ◽  
K. Dewar ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Genome Sequencing ◽  
Mechanisms Of Resistance

scholarly journals Experimental evolution of gallium resistance in Escherichia coli

2019 ◽  
Vol 2019 (1) ◽  
pp. 169-180
Author(s):  
Joseph L Graves ◽  
Akamu J Ewunkem ◽  
Jason Ward ◽  
Constance Staley ◽  
Misty D Thomas ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Experimental Evolution ◽  
Molecular Mechanisms ◽  
Gallium Nitrate ◽  
Whole Genome ◽  
Mechanisms Of Resistance ◽  
Genomic Changes ◽  
K 12

Abstract Background and Objectives Metallic antimicrobial materials are of growing interest due to their potential to control pathogenic and multidrug-resistant bacteria. Yet we do not know if utilizing these materials can lead to genetic adaptations that produce even more dangerous bacterial varieties. Methodology Here we utilize experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to, the iron analog, gallium nitrate (Ga(NO3)3). Whole genome sequencing was utilized to determine genomic changes associated with gallium resistance. Computational modeling was utilized to propose potential molecular mechanisms of resistance. Results By day 10 of evolution, increased gallium resistance was evident in populations cultured in medium containing a sublethal concentration of gallium. Furthermore, these populations showed increased resistance to ionic silver and iron (III), but not iron (II) and no increase in traditional antibiotic resistance compared with controls and the ancestral strain. In contrast, the control populations showed increased resistance to rifampicin relative to the gallium-resistant and ancestral population. Genomic analysis identified hard selective sweeps of mutations in several genes in the gallium (III)-resistant lines including: fecA (iron citrate outer membrane transporter), insl1 (IS30 tranposase) one intergenic mutations arsC →/→ yhiS; (arsenate reductase/pseudogene) and in one pseudogene yedN ←; (iapH/yopM family). Two additional significant intergenic polymorphisms were found at frequencies > 0.500 in fepD ←/→ entS (iron-enterobactin transporter subunit/enterobactin exporter, iron-regulated) and yfgF ←/→ yfgG (cyclic-di-GMP phosphodiesterase, anaerobic/uncharacterized protein). The control populations displayed mutations in the rpoB gene, a gene associated with rifampicin resistance. Conclusions This study corroborates recent results observed in experiments utilizing pathogenic Pseudomonas strains that also showed that Gram-negative bacteria can rapidly evolve resistance to an atom that mimics an essential micronutrient and shows the pleiotropic consequences associated with this adaptation. Lay summary We utilize experimental evolution to produce strains of Escherichia coli K-12 MG1655 resistant to, the iron analog, gallium nitrate (Ga(NO3)3). Whole genome sequencing was utilized to determine genomic changes associated with gallium resistance. Computational modeling was utilized to propose potential molecular mechanisms of resistance.

Domain organization and molecular characterization of 13 two-component systems identified by genome sequencing of Streptococcus pneumoniae

Gene ◽  
1999 ◽  
Vol 237 (1) ◽  
pp. 223-234 ◽  
Author(s):  
Roland Lange ◽  
Christian Wagner ◽  
Antoine de Saizieu ◽  
Nicholas Flint ◽  
Juliette Molnos ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Molecular Characterization ◽  
Genome Sequencing ◽  
Domain Organization ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

Forty years of helminth biochemistry

Parasitology ◽  
2009 ◽  
Vol 136 (12) ◽  
pp. 1633-1642 ◽  
Author(s):  
J. BARRETT
Keyword(s):  
Genome Sequencing ◽  
High Throughput ◽  
Mode Of Action ◽  
Mechanisms Of Resistance ◽  
Catabolic Pathways ◽  
Parasitic Helminths ◽  
Biological Relevance ◽  
New Information ◽  
The Future

SUMMARYThis review describes some of the developments in helminth biochemistry that have taken place over the last 40 years. Since the early 1970s the main anabolic and catabolic pathways in parasitic helminths have been worked out. The mode of action of the majority of anthelmintics is now known, but in many cases the mechanisms of resistance remain elusive. Developments in helminth biochemistry have depended heavily on developments in other areas. High throughput methods such as proteomics, transcriptomics and genome sequencing are now generating vast amounts of new data. The challenge for the future is to interpret and understand the biological relevance of this new information.

scholarly journals Cefiderocol Activity against Clinical Pseudomonas aeruginosa Isolates Exhibiting Ceftolozane-Tazobactam Resistance

2021 ◽  
Author(s):  
Patricia J Simner ◽  
Stephan Beisken ◽  
Yehudit Bergman ◽  
Andreas E Posch ◽  
Sara E Cosgrove ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Binding Sites ◽  
Whole Genome ◽  
The Novel ◽  
Broth Microdilution ◽  
Mechanisms Of Resistance ◽  
Fold Reduction ◽  
Target Binding

Abstract Objective Mutations in the AmpC-AmpR region are associated with treatment-emergent ceftolozane-tazobactam (TOL-TAZ) and ceftazidime-avibactam (CAZ-AVI) resistance. We sought to determine if these mutations impact susceptibility to the novel cephalosporin-siderophore compound cefiderocol. Methods Thirty-two paired isolates from 16 patients with index P. aeruginosa isolates susceptible to TOL-TAZ and subsequent P. aeruginosa isolates available after TOL-TAZ exposure from January 2019 to December 2020 were included. TOL-TAZ, CAZ-AVI, imipenem-relebactam (IMI-REL), and cefiderocol minimum inhibitory concentrations (MICs) were determined using broth microdilution. Whole genome sequencing of paired isolates was used to identify mechanisms of resistance to cefiderocol that emerged, focusing on putative mechanisms of resistance to cefiderocol or earlier siderophore-antibiotic conjugates based on the previously published literature. Results Analyzing the 16 pairs of P. aeruginosa isolates, ≥4-fold increases in cefiderocol MICs occurred in 4 of 16 isolates. Cefiderocol non-susceptibility criteria was met for only 1 of the 4 isolates, using Clinical and Laboratory Standards Institute criteria. Specific mechanisms identified included the following: AmpC E247K (2 isolates), MexR A66V and L57D (1 isolate each), and AmpD G116D (1 isolate) substitutions. For both isolates with AmpC E247K mutations, ≥4-fold MIC increases occurred for both TOL-TAZ and CAZ-AVI, while a ≥4-fold reduction in IMI-REL MICs was observed. Conclusions Our findings suggest that alterations in the target binding sites of P. aeruginosa derived AmpC β-lactamases have the potential to reduce the activity of three of four novel β-lactams (i.e., ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol) and potentially increase susceptibility to imipenem-relebactam. These findings are in need of validation in a larger cohort.

scholarly journals SeroBA: rapid high-throughput serotyping of Streptococcus pneumoniae from whole genome sequence data

2017 ◽  
Author(s):  
Lennard Epping ◽  
Andries J. van Tonder ◽  
Rebecca A. Gladstone ◽  
Stephen D. Bentley ◽  
Andrew J. Page ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome Sequence ◽  
Validation Dataset ◽  
List Type ◽  
Whole Genome ◽  
Link Type ◽  
Computational Performance ◽  
The Impact

ABSTRACTStreptococcus pneumoniae is responsible for 240,000 - 460,000 deaths in children under 5 years of age each year. Accurate identification of pneumococcal serotypes is important for tracking the distribution and evolution of serotypes following the introduction of effective vaccines. Recent efforts have been made to infer serotypes directly from genomic data but current software approaches are limited and do not scale well. Here, we introduce a novel method, SeroBA, which uses a hybrid assembly and mapping approach. We compared SeroBA against real and simulated data and present results on the concordance and computational performance against a validation dataset, the robustness and scalability when analysing a large dataset, and the impact of varying the depth of coverage in the cps locus region on sequence-based serotyping. SeroBA can predict serotypes, by identifying the cps locus, directly from raw whole genome sequencing read data with 98% concordance using a k-mer based method, can process 10,000 samples in just over 1 day using a standard server and can call serotypes at a coverage as low as 10x. SeroBA is implemented in Python3 and is freely available under an open source GPLv3 license from: https://github.com/sanger-pathogens/seroba.DATA SUMMARYThe reference genome Streptococcus pneumoniae ATCC 700669 is available from National Center for Biotechnology Information (NCBI) with the accession number: FM211187Simulated paired end reads for experiment 2 have been deposited in FigShare: https://doi.org/10.6084/m9.figshare.5086054.v1Accession numbers for all other experiments are listed in Supplementary Table S1 and Supplementary Table S2.I/We confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. ⊠IMPACT STATEMENTThis article describes SeroBA, a A-mer based method for predicting the serotypes of Streptococcus pneumoniae from Whole Genome Sequencing (WGS) data. SeroBA can identify 92 serotypes and 2 subtypes with constant memory usage and low computational costs. We showed that SeroBA is able to reliably predict serotypes at a depth of coverage as low as 10x and is scalable to large datasets.

Genome sequencing reveals thatStreptococcus pneumoniaepossesses a large and diverse repertoire of antimicrobial toxins

2017 ◽  
Author(s):  
Reza Rezaei Javan ◽  
Andries J van Tonder ◽  
James P King ◽  
Caroline L Harrold ◽  
Angela B Brueggemann
Keyword(s):  
Streptococcus Pneumoniae ◽  
Molecular Epidemiology ◽  
Genome Sequencing ◽  
Gene Clusters ◽  
Morbidity And Mortality ◽  
Streptococcal Species ◽  
Bacteriocin Gene ◽  
Bacteriocin Genes

AbstractStreptococcus pneumoniae(‘pneumococcus’) is a leading cause of morbidity and mortality worldwide and a frequent coloniser of the nasopharynx. Competition among bacterial members of the nasopharynx is believed to be mediated by bacteriocins: antimicrobial toxins produced by bacteria to inhibit growth of other bacteria. Bacteriocins are also promising candidates for novel antimicrobials. Here, 14 newly-discovered bacteriocin gene clusters were identified among >6,200 pneumococcal genomes. The molecular epidemiology of the bacteriocin clusters was investigated using a large global and historical pneumococcal dataset. The analyses revealed extraordinary bacteriocin diversity among pneumococci and the majority of bacteriocin clusters were also found in other streptococcal species. Genomic hotspots for the integration of bacteriocin genes were discovered. Experimentally, bacteriocin genes were transcriptionally active when the pneumococcus was under stress and when two strains were competing in broth co-culture. These findings fundamentally expand our understanding of bacteriocins relative to intraspecies and interspecies nasopharyngeal competition.

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