scholarly journals Genome sequencing and molecular characterisation of XDR Acinetobacter baumannii reveal complexities in resistance: Novel combination of Sulbactam-Durlobactam holds promise for therapeutic intervention

2021 ◽  
Author(s):  
Aniket Naha ◽  
Saranya Vijayakumar ◽  
Binesh Lal ◽  
Baby Abirami Shankar ◽  
Suriya Chandran ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Genome Sequencing ◽  
Interaction Analysis ◽  
Backbone Dynamics ◽  
Molecular Characterisation ◽  
Binding Affinities ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Protein Backbone Dynamics ◽  
Extensive Drug Resistance

Acinetobacter baumannii is an emerging nosocomial strain expressing extensive drug resistance (XDR). Whole-genome sequencing and molecular characterisation analysis revealed the presence of carbapenemase in 92.86% of studied Indian isolates having blaOXA-51, blaOXA-23, blaOXA-58, and blaNDM genes, with a few evidences of dual carbapenemase genes. As per the MLST scheme, IC2Oxf/CC2Pas was the predominant clone, with 57.14% isolates belonging to this lineage. The presence of β-lactamases has rendered sulbactam (SUL) resistance (MIC: 16-256μg/ml) in all the studied isolates. The efficacy of novel durlobactam (DUR) in inhibiting β-lactamases and PBP2 was assessed through in-silico inter-molecular interaction analysis. Several non-synonymous single nucleotide polymorphisms (nsSNPs) were identified in PBP2 (G264S, I108V, S259T) and PBP3 (A515V, T526S) sequences. Minimal variations were recorded in the protein-backbone dynamics in active-site motifs of wild-type (WT) and mutants (MT), which correlated with the negligible binding energy fluctuations for PBP3-SUL (-5.85±.04Kcal/mol) and PBP2-DUR (-5.16±0.66Kcal/mol) complexes. Furthermore, stronger binding affinities and low inhibition constants were noted in DUR complexed with OXA23 (-7.36Kcal/mol; 4.01 μM), OXA58 (-6.44Kcal/mol; 19.07 μM) and NDM (-6.82Kcal/mol; 10.01 μM) when compared with conventional drugs avibactam and aztreonam. Stable interaction profiles of DUR, can possibly restore SUL activity against both PBP3WT and PBP3MTs. The study establishes the efficacy of novel SUL-DUR combination as a successful treatment strategy to combat emerging XDR strains.

scholarly journals Mycobacterium chimaera genomics with regard to epidemiological and clinical investigations conducted for the open-chest post-surgical Mycobacterium chimaera infections outbreak

2021 ◽  
Author(s):  
Emmanuel Lecorche ◽  
Côme Daniau ◽  
Kevin La ◽  
Faiza Mougari ◽  
Hanaa Benmansour ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Clinical Isolates ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Healthcare Facilities ◽  
Open Chest

Abstract Background Post-surgical infections due to Mycobacterium chimaera appeared as a novel nosocomial threat in 2015, with a worldwide outbreak due to contaminated heater-cooler units used in open chest surgery. We report the results of investigations conducted in France including whole genome sequencing comparison of patient and HCU isolates. Methods We sought M. chimaera infection cases from 2010 onwards through national epidemiological investigations in healthcare facilities performing cardiopulmonary bypass together with a survey on good practices and systematic heater-cooler unit microbial analyses. Clinical and HCU isolates were subjected to whole genome sequencing analyzed with regards to the reference outbreak strain Zuerich-1. Results Only two clinical cases were shown to be related to the outbreak, although 23% (41/175) heater-cooler units were declared positive for M. avium complex. Specific measures to prevent infection were applied in 89% (50/56) healthcare facilities although only 14% (8/56) of them followed the manufacturer maintenance recommendations. Whole genome sequencing comparison showed that the clinical isolates and 72% (26/36) of heater-cooler unit isolates belonged to the epidemic cluster. Within clinical isolates, 5 to 9 non-synonymous single nucleotide polymorphisms were observed, among which an in vivo mutation in a putative efflux pump gene observed in a clinical isolate obtained for one patient under antimicrobial treatment. Conclusions Cases of post-surgical M. chimaera infections were declared to be rare in France, although heater-cooler units were contaminated as in other countries. Genomic analyses confirmed the connection to the outbreak and identified specific single nucleotide polymorphisms, including one suggesting fitness evolution in vivo.

scholarly journals Application of Whole Genome Sequencing to Understand Diversity and Presence of Genes Associated with Sanitizer Tolerance in Listeria monocytogenes from Produce Handling Sources

Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2454
Author(s):  
Rebecca N. Bland ◽  
Jared D. Johnson ◽  
Joy G. Waite-Cusic ◽  
Alexandra J. Weisberg ◽  
Elizabeth R. Riutta ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Phenotype Screening ◽  
Screening Assays ◽  
Contamination Events ◽  
Sequence Types ◽  
Potential Use

Recent listeriosis outbreaks linked to fresh produce suggest the need to better understand and mitigate L. monocytogenes contamination in packing and processing environments. Using whole genome sequencing (WGS) and phenotype screening assays for sanitizer tolerance, we characterized 48 L. monocytogenes isolates previously recovered from environmental samples in five produce handling facilities. Within the studied population there were 10 sequence types (STs) and 16 cgMLST types (CTs). Pairwise single nucleotide polymorphisms (SNPs) ranged from 0 to 3047 SNPs within a CT, revealing closely and distantly related isolates indicative of both sporadic and continuous contamination events within the facility. Within Facility 1, we identified a closely related cluster (0–2 SNPs) of isolates belonging to clonal complex 37 (CC37; CT9492), with isolates recovered during sampling events 1-year apart and in various locations inside and outside the facility. The accessory genome of these CC37 isolates varied from 94 to 210 genes. Notable genetic elements and mutations amongst the isolates included the bcrABC cassette (2/48), associated with QAC tolerance; mutations in the actA gene on the Listeria pathogenicity island (LIPI) 1 (20/48); presence of LIPI-3 (21/48) and LIPI-4 (23/48). This work highlights the potential use of WGS in tracing the pathogen within a facility and understanding properties of L. monocytogenes in produce settings.

scholarly journals In-Depth Study of a Nosocomial Outbreak Caused by Extensively Drug-Resistant Pseudomonas aeruginosa Using Whole Genome Sequencing Coupled With a Polymerase Chain Reaction Targeting Strain-Specific Single Nucleotide Polymorphisms

2020 ◽  
Vol 189 (8) ◽  
pp. 841-849
Author(s):  
Fermín Acosta ◽  
Ana Fernández-Cruz ◽  
Sandra R Maus ◽  
Pedro J Sola-Campoy ◽  
Mercedes Marín ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Outbreak Strain ◽  
Single Nucleotide ◽  
Specific Pcr ◽  
Extensively Drug Resistant ◽  
Polymerase Chain

Abstract In 2013–2014, an outbreak involving 14 patients infected by an extensively drug-resistant strain of Pseudomonas aeruginosa was detected in a hospital in Madrid, Spain. Our objective was to evaluate an alternative strategy for investigating the outbreak in depth by means of molecular and genomic approaches. Pulsed-field gel electrophoresis (PFGE) was applied as a first-line approach, followed by a more refined whole genome sequencing analysis. Single nucleotide polymorphisms identified by whole genome sequencing were used to design a specific polymerase chain reaction (PCR) for screening unsuspected cases infected by the outbreak strain. Whole genome sequencing alerted us to the existence of greater genetic diversity than was initially assumed, splitting the PFGE-associated outbreak isolates into 4 groups, 2 of which represented coincidental transmission unrelated to the outbreak. A multiplex allele-specific PCR targeting outbreak-specific single nucleotide polymorphisms was applied to 290 isolates, which allowed us to identify 25 additional cases related to the outbreak during 2011–2017. Whole genome sequencing coupled with an outbreak-strain-specific PCR enabled us to markedly redefine the initial picture of the outbreak by 1) ruling out initially suspected cases, 2) defining likely independent coincidental transmission events, 3) predating the starting point of the outbreak, 4) capturing new unsuspected cases, and 5) revealing that the outbreak was still active.

5,10-Methylenetetrahydrofolate reductase single nucleotide polymorphisms and gene-environment interaction analysis in non-syndromic cleft lip/palate

2014 ◽  
Vol 122 (2) ◽  
pp. 109-113 ◽  
Author(s):  
Bernardette Estandia-Ortega ◽  
José A. Velázquez-Aragón ◽  
Miguel A. Alcántara-Ortigoza ◽  
Miriam E. Reyna-Fabian ◽  
Sandra Villagómez-Martínez ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Cleft Lip ◽  
Methylenetetrahydrofolate Reductase ◽  
Interaction Analysis ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Cleft Lip Palate

scholarly journals Whole genome sequencing reveals extensive community-level transmission of group AStreptococcusin remote communities

2016 ◽  
Vol 144 (9) ◽  
pp. 1991-1998 ◽  
Author(s):  
A. C. BOWEN ◽  
T. HARRIS ◽  
D. C. HOLT ◽  
P. M. GIFFARD ◽  
J. R. CARAPETIS ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Remote Communities ◽  
Single Nucleotide ◽  
Indigenous Children ◽  
Primary Driver ◽  
Group A ◽  
Sequence Types

SUMMARYImpetigo is common in remote Indigenous children of northern Australia, with the primary driver in this context beingStreptococcus pyogenes[or group AStreptococcus(GAS)]. To reduce the high burden of impetigo, the transmission dynamics of GAS must be more clearly elucidated. We performed whole genome sequencing on 31 GAS isolates collected in a single community from children in 11 households with ⩾2 GAS-infected children. We aimed to determine whether transmission was occurring principally within households or across the community. The 31 isolates were represented by nine multilocus sequence types and isolates within each sequence type differed from one another by only 0–3 single nucleotide polymorphisms. There was evidence of extensive transmission both within households and across the community. Our findings suggest that strategies to reduce the burden of impetigo in this setting will need to extend beyond individual households, and incorporate multi-faceted, community-wide approaches.

scholarly journals Whole Genome Sequencing of Nontuberculous Mycobacterium (NTM) Isolates from Sputum and Environmental Specimens in Co-Habiting Patients with NTM Pulmonary Disease

2019 ◽  
Author(s):  
Jung-Ki Yoon ◽  
Taek Soo Kim ◽  
Jong-Il Kim ◽  
Jae-Joon Yim
Keyword(s):  
Whole Genome Sequencing ◽  
Pulmonary Disease ◽  
Genome Sequencing ◽  
Genetic Distances ◽  
Mycobacterium Abscessus ◽  
Nontuberculous Mycobacterium ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Next Generation Sequencing Ngs

Abstract Background : Nontuberculous mycobacterium (NTM) species are ubiquitous microorganisms. NTM pulmonary disease (NTM-PD) is caused not by human-to-human transmission but by independent environmental acquisition. However, recent studies using next-generation sequencing (NGS) have reported trans-continental spread of Mycobacterium abscessus among patients with cystic fibrosis. Results : We investigated NTM genomes through NGS to examine transmission patterns in three pairs of co-habiting NTM-PD patients who were suspected of patient-to-patient transmission. Three pairs of patients with NTM-PD co-habiting for at least 15 years were enrolled: a mother and a daughter with M. avium PD, a couple with M. intracellulare PD, and a second couple, one of whom was infected with M. intracellulare PD and the other of whom was infected with M. abscessus subsp. massiliense PD. Whole genome sequencing was performed using NTM colonies isolated from patients and environmental specimens. Genetic distances were estimated based on single nucleotide polymorphisms (SNPs) in the NTM genomes. Comparing SNPs in the consensus regions, the minimum pairwise SNP distances of NTM isolates derived from the two pairs of patients infected with the same NTM species were over 10,000. In phylogenetic analysis, the NTM isolates from patients with M. avium PD clustered with isolates from different environmental sources. Conclusions : In conclusion, considering the genetic distances between NTM strains, the likelihood of patient-to-patient transmission in pairs of co-habiting NTM-PD patients without overt immune deficiency is minimal.

Abstract P127: Gene-Lifestyle Interactions Detect Novel Blood Pressure Loci

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Oyomoare L Osazuwa-Peters ◽  
Karen L Schwander ◽  
Yun J Sung ◽  
Lisa de las Fuentes ◽  
Dabeeru C Rao
Keyword(s):  
Blood Pressure ◽  
Interaction Analysis ◽  
Smoking Status ◽  
Interaction Effects ◽  
Lifestyle Factors ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Heart Study

Introduction: Gene-lifestyle interaction effects (GxE more generally) on blood pressure (BP), a promising approach for novel loci discovery, is being actively pursued in the CHARGE Gene-Lifestyle Interactions Working Group using individual lifestyle domains, such as smoking status. Objectives: To explore the potential utility of a “lifestyle index” (aggregating multiple lifestyle domains) for identifying novel BP loci in a GxE context, we performed genome-wide interaction analysis with two lifestyle index variables. Methods: For each of 6,257 subjects (19 – 80 years, 46.9% male) in the Framingham Heart Study SHARe dataset, lifestyle index was defined as the sum of risk scores for four lifestyle factors: smoking status (0 = Never, 1 = Former, 2 = Current), alcohol intake (0 = Moderate, 1 = Never, 2 = Heavy), physical activity (0 = Active, 1= Inactive), and educational level (0=College degree, 1 = Some college, and 2 = No college). We examined GxE for systolic BP using the quantitative index (ranging from 0 to 7) and a binary form of the index (≥ vs < the median), while adjusting for sex, age, and kinship. Promising loci were identified using a 2 df joint test of main and interaction effects at α = 5 x 10 -6 . Results: Sixteen promising single nucleotide polymorphisms (SNPs) representing 8 loci were found when using the quantitative lifestyle index, and 43 SNPs representing 4 loci when using the binary lifestyle index (Table 1), with only one locus common to both indices. Of the 11 unique loci detected, 3 are within 500 kb of known BP loci and 6 are in or near a gene with a known function. Conclusions: We demonstrate that a composite of multiple lifestyle factors can enhance novel discovery.

Bioinformatics-Driven Big Data Analytics in Microbial Research

2015 ◽  
pp. 265-283 ◽  
Author(s):  
Ratna Prabha ◽  
Anil Rai ◽  
D. P. Singh
Keyword(s):  
Big Data ◽  
Data Storage ◽  
Genome Sequencing ◽  
Big Data Analytics ◽  
Biological Data ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Huge Data ◽  
Computational Resources

With the advent of sophisticated and high-end molecular biological technologies, microbial research has observed tremendous boom. It has now become one of the most prominent sources for the generation of “big data.” This is made possible due to huge data coming from the experimental platforms like whole genome sequencing projects, microarray technologies, mapping of Single Nucleotide Polymorphisms (SNP), proteomics, metabolomics, and phenomics programs. For analysis, interpretation, comparison, storage, archival, and utilization of this wealth of information, bioinformatics has emerged as a massive platform to solve the problems of data management in microbial research. In present chapter, the authors present an account of “big data” resources spread across the microbial domain of research, the efforts that are being made to generate “big data,” computational resources facilitating analysis and interpretation, and future needs for huge biological data storage, interpretation, and management.

Sign in / Sign up

Export Citation Format

Share Document