scholarly journals Representing Genetic Determinants in Bacterial GWAS with Compacted De Bruijn Graphs

2017 ◽  
Author(s):  
Magali Jaillard ◽  
Maud Tournoud ◽  
Leandro Lima ◽  
Vincent Lacroix ◽  
Jean-Baptiste Veyrieras ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Pathogenic Bacteria ◽  
Resistance Mechanisms ◽  
Health Concern ◽  
Genetic Determinants ◽  
De Bruijn Graphs ◽  
De Bruijn ◽  
Marker Discovery ◽  
Core Genes

AbstractMotivationAntimicrobial resistance has become a major worldwide public health concern, calling for a better characterization of existing and novel resistance mechanisms. GWAS methods applied to bacterial genomes have shown encouraging results for new genetic marker discovery. Most existing approaches either look at SNPs obtained by sequence alignment or consider sets of kmers, whose presence in the genome is associated with the phenotype of interest. While the former approach can only be performed when genomes are similar enough for an alignment to make sense, the latter can lead to redundant descriptions and to results which are hard to interpret.ResultsWe propose an alignment-free GWAS method detecting haplotypes of variable length associated to resistance, using compacted De Bruijn graphs. Our representation is flexible enough to deal with very plastic genomes subject to gene transfers while drastically reducing the number of features to explore compared to kmers, without loss of information. It accomodates polymorphisms in core genes, accessory genes and noncoding regions. Using our representation in a GWAS leads to the selection of a small number of entities which are easier to visualize and interpret than fixed-length kmers. We illustrate the benefit of our approach by describing known as well as potential novel determinants of antimicrobial resistance in P. aeruginosa, a pathogenic bacteria with a highly plastic genome.Availability and implementationThe code and data used in the experiments will be made available upon acceptance of this [email protected]

scholarly journals The Maximum Independent Sets of de Bruijn Graphs of Diameter 3

10.37236/681 ◽  
2011 ◽  
Vol 18 (1) ◽  
Author(s):  
Dustin A. Cartwright ◽  
María Angélica Cueto ◽  
Enrique A. Tobis
Keyword(s):  
Recurrence Relation ◽  
Generating Function ◽  
Independent Sets ◽  
De Bruijn Graph ◽  
Alphabet Size ◽  
De Bruijn Graphs ◽  
Exponential Generating Function ◽  
De Bruijn

The nodes of the de Bruijn graph $B(d,3)$ consist of all strings of length $3$, taken from an alphabet of size $d$, with edges between words which are distinct substrings of a word of length $4$. We give an inductive characterization of the maximum independent sets of the de Bruijn graphs $B(d,3)$ and for the de Bruijn graph of diameter three with loops removed, for arbitrary alphabet size. We derive a recurrence relation and an exponential generating function for their number. This recurrence allows us to construct exponentially many comma-free codes of length 3 with maximal cardinality.

scholarly journals Antimicrobial resistance and metallo-beta-lactamase producing among commensal Escherichia coli isolates from healthy children of Khuzestan and Fars provinces; Iran 

2020 ◽  
Author(s):  
Fahimeh Mahmoodi ◽  
Seyedeh Elham Rezatofighi ◽  
Mohammad Reza Akhoond
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Pathogenic Bacteria ◽  
Gastrointestinal Diseases ◽  
Resistance Mechanisms ◽  
Multi Drug Resistance ◽  
Healthy Children ◽  
Great Ability ◽  
E Coli ◽  
Plasmid Profiling

Abstract Background: The emergence of metallo-β-lactamase (MBL)-producing isolates is alarming since they carry mobile genetic elements with great ability to spread; therefore, early detection of these isolates, particularly their reservoir, is crucial to prevent their inter- and intra-care setting dissemination and establish suitable antimicrobial therapies. The current study was designed to evaluate the frequency of antimicrobial resistance (AMR), MBL producers and identification of MBL resistance genes in Escherichia coli strains isolated from fecal samples of the healthy children under three years old. A total of 412 fecal E. coli isolates were collected from October 2017 to December 2018. The study population included healthy infants and children aged <3 years who did not exhibit symptoms of any diseases, especially gastrointestinal diseases. E. coli isolates were assessed to determine the pattern of AMR. E. coli isolates were assessed to determine the pattern of AMR, the production of extended spectrum β-lactamase (ESBL) and MBL by phenotypic methods. Carbapenem-resistant isolates were investigated for the presence of MBL and carbapenemase genes, plasmid profiling, and the ability of conjugation.Results: In sum, AMR, multi-drug resistance (MDR) and ESBL production were observed in more than 54.9%, 36.2% and 11.7% of commensal E. coli isolates, respectively. Out of six isolates resistant to imipenem and meropenem, four isolates were phenotypically detected as MBL producers. Two and one E. coli strains carried the blaNDM-1 and blaVIM-2 genes, respectively and were able to transmit imipenem resistance through conjugation. Conclusion: Our findings showed that children not exposed to antibiotics can be colonized by E. coli isolates resistant to the commonly used antimicrobial compounds and can be a good indicator for the occurrence and prevalence of AMR in the community. These bacteria can act as a potential reservoir of AMR genes including MBL genes of pathogenic bacteria and lead to the dissemination of resistance mechanisms to other bacteria.

scholarly journals 4-Amino-2-Sulfanylbenzoic Acid as a Potent Subclass B3 Metallo-β-Lactamase-Specific Inhibitor Applicable for Distinguishing Metallo-β-Lactamase Subclasses

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Jun-ichi Wachino ◽  
Reo Kanechi ◽  
Erina Nishino ◽  
Marie Mochizuki ◽  
Wanchun Jin ◽  
...  
Keyword(s):  
Specific Inhibitor ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Health Concern ◽  
Conserved Residues ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Promising Strategy ◽  
Starting Point

ABSTRACT The number of cases of infection with carbapenem-resistant Enterobacteriaceae (CRE) has been increasing and has become a major clinical and public health concern. Production of metallo-β-lactamases (MBLs) is one of the principal carbapenem resistance mechanisms in CRE. Therefore, developing MBL inhibitors is a promising strategy to overcome the problems of carbapenem resistance conferred by MBLs. To date, the development and evaluation of MBL inhibitors have focused on subclass B1 MBLs but not on B3 MBLs. In the present study, we searched for B3 MBL (specifically, SMB-1) inhibitors and found thiosalicylic acid (TSA) to be a potent inhibitor of B3 SMB-1 MBL (50% inhibitory concentration [IC50], 0.95 μM). TSA inhibited the purified SMB-1 to a considerable degree but was not active against Escherichia coli cells producing SMB-1, as the meropenem (MEM) MIC for the SMB-1 producer was only slightly reduced with TSA. We then introduced a primary amine to TSA and synthesized 4-amino-2-sulfanylbenzoic acid (ASB), which substantially reduced the MEM MICs for SMB-1 producers. X-ray crystallographic analyses revealed that ASB binds to the two zinc ions, Ser221, and Thr223 at the active site of SMB-1. These are ubiquitously conserved residues across clinically relevant B3 MBLs. ASB also significantly inhibited other B3 MBLs, including AIM-1, LMB-1, and L1. Therefore, the characterization of ASB provides a starting point for the development of optimum B3 MBL inhibitors.

scholarly journals An overview of antimicrobial resistance surveillance among healthcare-associated pathogens in South Africa

2018 ◽  
Vol 7 (2) ◽  
Author(s):  
Ashika Singh-Moodley ◽  
Husna Ismail ◽  
Olga Perovic
Keyword(s):  
Antimicrobial Resistance ◽  
Treatment Guidelines ◽  
Resistance Mechanisms ◽  
Health Concern ◽  
Infection Prevention And Control ◽  
Surveillance Systems ◽  
African Countries ◽  
Lack Of Information ◽  
Healthcare Associated ◽  
And Control

Healthcare-associated infections are a serious public health concern resulting in morbidity and mortality particularly in developing countries. The lack of information from Africa, the increasing rates of antimicrobial resistance and the emergence of new resistance mechanisms intensifies this concern warranting the need for vigorous standardised surveillance platforms that produce reliable and accurate data which can be used for addressing these concerns. The implementation of national treatment guidelines, policies, antimicrobial stewardship programmes and infection prevention and control practices within healthcare institutions require a platform from which it can draw information and direct its approach. In this review, the importance of standardised surveillance systems, the challenges faced in the application of a surveillance system and the condition (existence and nonexistence) of such systems in African countries is discussed. This review also reports on some South African data.

scholarly journals Carcass Salmonella and Its Drug Resistance

2019 ◽  
pp. 1-21
Author(s):  
Gizachew Muluneh Amera ◽  
Amit Kumar Singh
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Personal Hygiene ◽  
Wide Range ◽  
Food Animals

Salmonella are the major pathogenic bacteria in humans as well as in animals. Salmonella species are leading causes of acute gastroenteritis in several countries and salmonellosis remains an important public health problem worldwide, particularly in the developing countries. Isolation of Salmonella from a wide range of sources suggests that Salmonella is widespread in food animals and meat products and underlines the necessity for a joint and coordinated surveillance and monitoring programs for salmonellosis and other major food borne zoonotic diseases. Food animals harbor a wide range of Salmonella and so act as sources of contamination, which is of paramount epidemiological importance in non-typhoid human salmonellosis. Salmonellosis is more aggravated by the ever increasing rate of antimicrobial resistance strains in food animals. The high prevalence and dissemination of multidrug resistant (MDR) Salmonella have become a growing public health concern. Multidrug resistant (MDR) strains of Salmonella are now encountered frequently and the rates of multidrug resistance have increased considerably in recent years. Food animal consumption is a potential cause for antimicrobial resistant Salmonella illnesses besides, the common factors such as overcrowding, poverty, inadequate sanitary conditions, and poor personal hygiene. Practicing good sanitary measures, extensive education programs for proper hygiene and improvement of managements are solutions to eliminate the high bacteriological load as well as prevalence of Salmonella in cattle carcass. Furthermore, restricting the use of antimicrobial agents in food animals, designation of multidrug-resistant Salmonella as an adulterant in ground beef, improving the mechanisms for product trace-back investigations and wise and discriminate use of antimicrobials should be practiced to combat the ever increasing situation of antimicrobial resistance. So, this review used for updating information on their prevalence and resistance patterns is very important to suggest the acceptance of the carcass in relation to the standards and for proper selection and use of antimicrobial agents in a setting.

scholarly journals Characterization of antimicrobial resistance mechanisms in carbapenem-resistant Pseudomonas aeruginosa carrying IMP variants recovered from a Mexican Hospital

2018 ◽  
Vol Volume 11 ◽  
pp. 1523-1536 ◽  
Author(s):  
Alma López-García ◽  
Rosa del Carmen Rocha-Gracia ◽  
Elena Bello-López ◽  
Claudia Juárez-Zelocualtecalt ◽  
Yolanda Sáenz ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Resistance Mechanisms ◽  
Carbapenem Resistant

scholarly journals Metagenome SNP calling via read-colored de Bruijn graphs

2020 ◽  
Author(s):  
Bahar Alipanahi ◽  
Martin D Muggli ◽  
Musa Jundi ◽  
Noelle R Noyes ◽  
Christina Boucher
Keyword(s):  
Pathogenic Bacteria ◽  
Read Length ◽  
Supplementary Information ◽  
De Bruijn Graph ◽  
Nucleotide Polymorphisms ◽  
Chromosomal Dna ◽  
Shotgun Metagenomics ◽  
De Bruijn Graphs ◽  
De Bruijn ◽  
Colored De Bruijn Graph

Abstract Motivation Metagenomics refers to the study of complex samples containing of genetic contents of multiple individual organisms and, thus, has been used to elucidate the microbiome and resistome of a complex sample. The microbiome refers to all microbial organisms in a sample, and the resistome refers to all of the antimicrobial resistance (AMR) genes in pathogenic and non-pathogenic bacteria. Single-nucleotide polymorphisms (SNPs) can be effectively used to ‘fingerprint’ specific organisms and genes within the microbiome and resistome and trace their movement across various samples. However, to effectively use these SNPs for this traceability, a scalable and accurate metagenomics SNP caller is needed. Moreover, such an SNP caller should not be reliant on reference genomes since 95% of microbial species is unculturable, making the determination of a reference genome extremely challenging. In this article, we address this need. Results We present LueVari, a reference-free SNP caller based on the read-colored de Bruijn graph, an extension of the traditional de Bruijn graph that allows repeated regions longer than the k-mer length and shorter than the read length to be identified unambiguously. LueVari is able to identify SNPs in both AMR genes and chromosomal DNA from shotgun metagenomics data with reliable sensitivity (between 91% and 99%) and precision (between 71% and 99%) as the performance of competing methods varies widely. Furthermore, we show that LueVari constructs sequences containing the variation, which span up to 97.8% of genes in datasets, which can be helpful in detecting distinct AMR genes in large metagenomic datasets. Availability and implementation Code and datasets are publicly available at https://github.com/baharpan/cosmo/tree/LueVari. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Molecular and Clinical Characterization of Multidrug-Resistant and Hypervirulent Klebsiella pneumoniae Strains from Liver Abscess in Taiwan

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Yi-Tsung Lin ◽  
Yi-Hsiang Cheng ◽  
Chien Chuang ◽  
Sheng-Hua Chou ◽  
Wan-Hsin Liu ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Liver Abscess ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Virulence Plasmid ◽  
Content Type ◽  
Sequence Types

ABSTRACT Hypervirulent Klebsiella pneumoniae strains are the major cause of liver abscesses throughout East Asia, and these strains are usually antibiotic susceptible. Recently, multidrug-resistant and hypervirulent (MDR-HV) K. pneumoniae strains have emerged due to hypervirulent strains acquiring antimicrobial resistance determinants or the transfer of a virulence plasmid into a classic MDR strain. In this study, we characterized the clinical and microbiological properties of K. pneumoniae liver abscess (KPLA) caused by MDR-HV strains in Taiwan. Patients with community onset KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 to May 2018. Antimicrobial resistance mechanisms, capsular types, and sequence types were determined. MDR-HV strains and their parental antimicrobial-susceptible strains further underwent whole-genome sequencing (WGS) and in vivo mice lethality tests. Thirteen MDR-HV strains were identified from a total of 218 KPLA episodes. MDR-HV strains resulted in similar outcomes to antimicrobial-susceptible strains. All MDR-HV strains were traditional hypervirulent clones carrying virulence capsular types. The major resistance mechanisms were the overexpression of efflux pumps and/or the acquisition of ESBL or AmpC β-lactamase genes. WGS revealed that two hypervirulent strains had evolved to an MDR phenotype due to mutation in the ramR gene and the acquisition of an SHV-12-bearing plasmid, respectively. Both these MDR-HV strains retained high virulence compared to their parental strains. The spread of MDR-HV K. pneumoniae strains in the community raises significant public concerns, and measures should be taken to prevent the further acquisition of carbapenemase and other resistance genes among these strains in order to avoid the occurrence of untreatable KPLA.

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