Comparative genomic analysis of multidrug-resistant &lt;em&gt;Streptococcus pneumoniae&lt;/em&gt; isolates

Pan, Fang; Zhang, Hong; Dong, Xiaoyan; Ye, Weixing; He, Ping; Zhang, Shulin; Zhu, Jeff Xianchao; Zhong, Nanbert

doi:10.2147/idr.s147858

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…In Mycobacterium tuberculosis short indels are shown to cause antibiotic resistance upon disruption which are not only dispensable and important in highly resistant outbreak but also important in evolution (Godfroid et al 2020). WGS of 25 clinical isolates of pneumococcal strains from children showed different drug resistant pro les ranging from 131-171 indels and SNPs in the range 16,103-28,128 with different drug resistant pro les (Pan et al 2018) however, the contribution of indels in antibiotic evolution is poorly understood.…”

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confidence: 99%

Ciprofloxacin induced antibiotic resistance in Salmonella Typhimurium mutants and genome analysis

2021

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Salmonella species is an important food-borne pathogen. Cipro oxacin is used for treatment of salmonellosis. The wild type of Salmonella Typhimurium was exposed to 10-fold of minimal inhibitory concentration (MIC) of cipro oxacin. The survivors of the rst exposure were regrown. This regrown population was exposed to similar cipro oxacin treatment. After 20 repetitions of the antibiotic exposure, the survival population was evaluated for antibiotic resistance. The mutants had 100-fold more of the initial MIC. The mutants were of smaller size (0.7 ± 0.5 mm) with a lag phase of 70 min. These mutants were resistant to other antibiotics belonging to different classes but were sensitive to heat and osmotic stress. The whole genome sequencing (WGS) analysis of antibiotic resistant mutants revealed interesting mutation pattern. Total 40513 mutations were observed across the genome (total 3843 annotated genes). Relatively small percentage (5.2%) of mutations were non-synonymous. Four-fold more transitions were observed than transversions. Ratio of <1 transition vs transversion shows a positive selection for antibiotic resistant trait. Seven genes with over 50 mutations were observed. However, mutation distribution across the genome was relatively uniform. The important genes like dnaE, gyrA, iroC, metH and rpoB involved in antibiotic resistance had point mutations. The genome analysis showed that most affected pathways were transcription regulation, transmembrane transport, cell adhesion, pathogenesis, pilus assembly, oxidation-reduction mechanisms, phosphor-relay signal transduction and LPS biosynthesis. We propose that development resistance to cipro oxacin is because of the mutations in these genes.

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confidence: 99%

Ciprofloxacin induced antibiotic resistance in Salmonella Typhimurium mutants and genome analysis

2021

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“…Compared to this technique, whole genome sequencing (WGS) has a highest discriminatory power for bacterial genomes analysis. Indeed, WGS has increased power to establish the evolutionary relationships between close strains across the species [9]. Multiple studies have used the high-throughput WGS to investigate PCV impact and clustering pneumococcal populations into groups using genomic variation that reflect a recent evolutionary history [10][11][12][13].…”

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confidence: 99%

Whole genomic comparative analysis of Streptococcus pneumoniae serotype 1 isolates causing invasive and non-invasive infections among children under 5 years in Casablanca, Morocco

et al. 2021

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Background Streptococcus pneumoniae serotype 1 remains a leading cause of invasive pneumococcal diseases, even in countries with PCV-10/PCV-13 vaccine implementation. The main objective of this study, which is part of the Pneumococcal African Genome project (PAGe), was to determine the phylogenetic relationships of serotype 1 isolates recovered from children patients in Casablanca (Morocco), compared to these from other African countries; and to investigate the contribution of accessory genes and recombination events to the genetic diversity of this serotype. Results The genome average size of the six-pneumococcus serotype 1 from Casablanca was 2,227,119 bp, and the average content of coding sequences was 2113, ranging from 2041 to 2161. Pangenome analysis of the 80 genomes used in this study revealed 1685 core genes and 1805 accessory genes. The phylogenetic tree based on core genes and the hierarchical bayesian clustering analysis revealed five sublineages with a phylogeographic structure by country. The Moroccan strains cluster in two different lineages, the five invasive strains clusters altogether in a divergent clade distantly related to the non-invasive strain, that cluster with all the serotype 1 genomes from Africa. Conclusions The whole genome sequencing provides increased resolution analysis of the highly virulent serotype 1 in Casablanca, Morocco. Our results are concordant with previous works, showing that the phylogeography of S. pneumoniae serotype 1 is structured by country, and despite the small size (six isolates) of the Moroccan sample, our analysis shows the genetic cohesion of the Moroccan invasive isolates.

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“…Another TrkH point mutation was identified in a highly streptomycin-resistant Salmonella enterica strain ( Wistrand-Yuen et al, 2018 ). In addition, a point mutation in TrkH was identified in a Streptococcus pneumonia pneumococcal isolate resistant to non-aminoglycoside antibiotics ( Pan et al, 2018 ), and KtrA was found to confer resistance to aminoglycosides and fitness advantage during infection in Staphylococcus aureus ( Gries et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Fluorometric Liposome Screen for Inhibitors of a Physiologically Important Bacterial Ion Channel

et al. 2021

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The bacterial K+ homeostasis machinery is widely conserved across bacterial species, and different from that in animals. Dysfunction in components of the machinery has an impact on intracellular turgor, membrane potential, adaptation to changes in both extracellular pH and osmolarity, and in virulence. Using a fluorescence-based liposome flux assay, we have performed a high-throughput screen to identify novel inhibitors of the KtrAB ion channel complex from Bacillus subtilis, a component of the K+ homeostasis machinery that is also present in many bacterial pathogens. The screen identified 41 compounds that inhibited K+ flux and that clustered into eight chemical groups. Many of the identified inhibitors were found to target KtrAB with an in vitro potency in the low μM range. We investigated the mechanisms of inhibition and found that most molecules affected either the membrane component of the channel, KtrB alone or the full KtrAB complex without a preference for the functional conformation of the channel, thus broadening their inhibitory action. A urea derivative molecule that inhibited the membrane component of KtrAB affected cell viability in conditions in which KtrAB activity is essential. With this proof-of-concept study, we demonstrate that targeting components of the K+ homeostasis machinery has the potential as a new antibacterial strategy and that the fluorescence-based flux assay is a robust tool for screening chemical libraries.

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Comparative genomic analysis of multidrug-resistant <em>Streptococcus pneumoniae</em> isolates

Cited by 9 publications

References 33 publications

Ciprofloxacin induced antibiotic resistance in Salmonella Typhimurium mutants and genome analysis

Ciprofloxacin induced antibiotic resistance in Salmonella Typhimurium mutants and genome analysis

Whole genomic comparative analysis of Streptococcus pneumoniae serotype 1 isolates causing invasive and non-invasive infections among children under 5 years in Casablanca, Morocco

Fluorometric Liposome Screen for Inhibitors of a Physiologically Important Bacterial Ion Channel

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