scholarly journals Mode and dynamics of vanA-type vancomycin-resistance dissemination in Dutch hospitals

2020 ◽  
Author(s):  
Sergio Arredondo-Alonso ◽  
Janetta Top ◽  
Jukka Corander ◽  
Rob J.L. Willems ◽  
Anita C. Sch&uumlrch
Keyword(s):  
Gene Cluster ◽  
Pairwise Comparison ◽  
Multidrug Resistant ◽  
Vancomycin Resistance ◽  
Priority List ◽  
Genomic Epidemiology ◽  
Relative Contribution ◽  
Global Priority ◽  
Clonal Spread ◽  
Plasmid Dissemination

Background: Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans but also a causative agent of hospital-acquired infections. Resistance against glycopeptides and especially to vancomycin, a first-line antibiotic to treat infections with multidrug-resistant Gram-positive pathogens, has motivated the inclusion of E. faecium in the WHO global priority list. Vancomycin resistance can be conferred by the vanA gene cluster on the transposon Tn1546, which is frequently present in plasmids. The vanA gene cluster can be disseminated clonally but also horizontally either by plasmid dissemination or Tn1546 transposition between different genomic locations. Here, we reconstructed all nested genetic elements (clone, plasmid,transposon) to study how the dissemination of vanA-type vancomycin-resistance occurred in Dutch hospitals (2012-2015). Methods: We performed a retrospective study of the genomic epidemiology of 309 vancomycin-resistant E. faecium (VRE) isolates across 32 Dutch hospitals (2012-2015). Genomic information regarding clonality and Tn1546 characterisation was extracted using hierBAPS sequence clusters (SC) and TETyper, respectively. Plasmids were predicted using gplas in combination with a network approach based on shared k-mer content. This allowed determining all nested genomic elements (clone, plasmid and transposon) involved in the dissemination of the vanA gene cluster. Next, we conducted an "all vs. all" pairwise comparison between isolates sharing a potential epidemiological link to elucidate whether clonal, plasmid or Tn1546 spread accounted for the dissemination of vanA resistance. Results: The 309 VRE isolates belonged to 18 different SCs of which SC13 (n = 102, 33%), SC17 (n = 52,16.8%) and SC18 (n = 42, 13.6%) were predominant. We identified seven different plasmid types bearing the vanA gene cluster, four of which were highly similar (identity ~99%, coverage ~84%) to previously described complete plasmid sequences. We estimated that clonal dissemination contributed most (~45%) to the spread of vancomycin-resistance in Dutch hospitals, followed by Tn1546 mobilisation (~12%) and plasmid dissemination (~6%). Conclusions: The dissemination of the vanA gene cluster in Dutch hospitals between 2012 and 2015 was dominated by clonal spread. However, we also identified outbreak settings with high frequencies of Tn1546 transposition and/or plasmid dissemination in which the spread of resistance was mainly driven by horizontal gene transfer (HGT). This study demonstrates the feasibility of distinguishing between modes of dissemination with short-read data and provides one of the first quantitative assessments to estimate the relative contribution of nested genomic elements in the dissemination of vanA-type vancomycin-resistance cluster.

scholarly journals Mode and dynamics of vanA-type vancomycin resistance dissemination in Dutch hospitals

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sergio Arredondo-Alonso ◽  
Janetta Top ◽  
Jukka Corander ◽  
Rob J. L. Willems ◽  
Anita C. Schürch
Keyword(s):  
Gene Cluster ◽  
Pairwise Comparison ◽  
Vancomycin Resistance ◽  
Priority List ◽  
Genomic Epidemiology ◽  
Relative Contribution ◽  
Global Priority ◽  
Clonal Spread ◽  
Plasmid Dissemination ◽  
Epidemiological Link

Abstract Background Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans but also a causative agent of hospital-acquired infections. Resistance against glycopeptides and to vancomycin has motivated the inclusion of E. faecium in the WHO global priority list. Vancomycin resistance can be conferred by the vanA gene cluster on the transposon Tn1546, which is frequently present in plasmids. The vanA gene cluster can be disseminated clonally but also horizontally either by plasmid dissemination or by Tn1546 transposition between different genomic locations. Methods We performed a retrospective study of the genomic epidemiology of 309 vancomycin-resistant E. faecium (VRE) isolates across 32 Dutch hospitals (2012–2015). Genomic information regarding clonality and Tn1546 characterization was extracted using hierBAPS sequence clusters (SC) and TETyper, respectively. Plasmids were predicted using gplas in combination with a network approach based on shared k-mer content. Next, we conducted a pairwise comparison between isolates sharing a potential epidemiological link to elucidate whether clonal, plasmid, or Tn1546 spread accounted for vanA-type resistance dissemination. Results On average, we estimated that 59% of VRE cases with a potential epidemiological link were unrelated which was defined as VRE pairs with a distinct Tn1546 variant. Clonal dissemination accounted for 32% cases in which the same SC and Tn1546 variants were identified. Horizontal plasmid dissemination accounted for 7% of VRE cases, in which we observed VRE pairs belonging to a distinct SC but carrying an identical plasmid and Tn1546 variant. In 2% of cases, we observed the same Tn1546 variant in distinct SC and plasmid types which could be explained by mixed and consecutive events of clonal and plasmid dissemination. Conclusions In related VRE cases, the dissemination of the vanA gene cluster in Dutch hospitals between 2012 and 2015 was dominated by clonal spread. However, we also identified outbreak settings with high frequencies of plasmid dissemination in which the spread of resistance was mainly driven by horizontal gene transfer (HGT). This study demonstrates the feasibility of distinguishing between modes of dissemination with short-read data and provides a novel assessment to estimate the relative contribution of nested genomic elements in the dissemination of vanA-type resistance.

scholarly journals Abstract P-46: Structure of A. Baumannii Phage Tapaz, Revealed with Cryo-Electron Microscopy

2021 ◽  
Vol 11 (Suppl_1) ◽  
pp. S32-S33
Author(s):  
Andrey Moiseenko ◽  
Yueqi Wang ◽  
Daniil Litvinov ◽  
Anastasia Popova ◽  
Mikhail Shneider ◽  
...  
Keyword(s):  
Structural Information ◽  
Structural Diversity ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Particle Analysis ◽  
Tail Region ◽  
Homologous Proteins ◽  
Priority List ◽  
Global Priority

Background: Acinetobacter baumannii is an opportunistic pathogen and one of the six most important multidrug resistant microorganisms in hospitals worldwide. Some of its strains are resistant to most of the antibiotics, A. baumannii is included into the Priority 1 part of Global Priority List of Antibiotic-resistant Bacteria. Phage therapy is considered to be an alternative strategy to antibiotic treatments. Methods: A. baumannii strain NIPH601 cells were grown till OD6000.4 and infected with the phage at MOI 10:1. After complete lysis took place cell debris was spined down and phage particles were precipitated with the PEG6000 (final concentration 10% PEG 6000, 0.5 NaCl). Virus particles were collected by centrifugation, resuspended at SM buffer and applied on CsCl step gradient. Gradient was spinned down for 2 hours at 40000g and the fraction containing phage particles was collected and dialyzed against SM buffer. Purified phage particles were applied to Quantifoil 1.2/1.3 grids and plunge-froze in Vitrobot Mark IV (TFS) Micrographs were collected in HKU, Shenzhen campus with Titan Krios cryoelectron microscope (TFS), equipped with Gatan K3 direct electron detector. The micrographs were acquired with 1.06 Å pixel size and 1.5 um average defocus value in counting mode with 50 frames and 1.2 e/Å2/frame dose rate. All image processing was performed with Relion3.0 software, except for the particle picking step performed with cryolo. Results: Lytic A. baumannii phage TaPaz belongs to the family Myoviridae. BLAST search over NCBI “nr” (non-redundant) database revealed close homology with previously published sequences of Acinetobacter phage vB_AbaM_B9 and Acinetobacter phage BS46. However, no structural information about any homologous proteins was found among the PDB structures. The cryo-EM map was reconstructed with single particle analysis independently for the capsid, tail and baseplate regions. The capsid was reconstructed at 3.9 Å resolution with I3 symmetry applied (Fig. 1A). The baseplate region of the phage was reconstructed at 3.5 Å resolution with C3 symmetry (Fig. 1B). The tail region was reconstructed at 2.6 Å resolution with helical symmetry (Rise 36.4 Å, Twist 25.7 deg). Initial atomic model for the tail region was built from sequence with Deeptracer and was further refined in coot (Fig. 1C). Conclusion: We successfully obtained the near-atomic resolution structural map of phage TaPaz. The data obtained contribute to enhancing knowledge of structural diversity of bacterial viruses infecting A. baumannii.

scholarly journals An Optimized Synthetic-Bioinformatic Natural Product Antibiotic Sterilizes Multidrug-Resistant Acinetobacter baumannii-Infected Wounds

mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Xavier Vila-Farres ◽  
John Chu ◽  
Melinda A. Ternei ◽  
Christophe Lemetre ◽  
Steven Park ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Natural Product ◽  
Critical Role ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Priority List ◽  
Link Type ◽  
Global Priority

Natural product-inspired antibiotics have saved millions of lives and played a critical role in modern medicine. However, the emergence of drug-resistant pathogens is outpacing the rate at which new clinically useful antibiotics are being discovered. The lack of a means to combat infections caused by multidrug-resistant (MDR) Acinetobacter baumannii is of particular concern. The sharp increase in cases of MDR A. baumannii infections in recent years prompted the CDC (https://www.cdc.gov/drugresistance/biggest_threats.html) and WHO (http://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/) to list this pathogen as a “serious threat” and “critical pathogen,” respectively. Here we report a new antibiotic, paenimucillin C, active against Gram-negative bacterial pathogens, including many clinical isolates of MDR A. baumannii strains. Mechanistic studies point to membrane disruption leading to leakage of intracellular contents as its antibacterial mode of action. Paenimucillin C sterilizes MDR A. baumannii infections in a rat cutaneous wound model with no sign of rebound infection, providing a potential new therapeutic regimen.

scholarly journals Bacteremia Among Febrile Patients Attending Selected Healthcare Facilities in Ibadan, Nigeria

2019 ◽  
Vol 69 (Supplement_6) ◽  
pp. S466-S473 ◽  
Author(s):  
Oluwafemi Popoola ◽  
Aderemi Kehinde ◽  
Veronica Ogunleye ◽  
Oluwafemi J Adewusi ◽  
Trevor Toy ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Bacterial Infections ◽  
Common Species ◽  
Epidemiological Studies ◽  
Multidrug Resistant ◽  
African Countries ◽  
Healthcare Facilities ◽  
Relative Contribution ◽  
Polymerase Chain ◽  
Ibadan Nigeria

Abstract Background The relative contribution of bacterial infections to febrile disease is poorly understood in many African countries due to diagnostic limitations. This study screened pediatric and adult patients attending 4 healthcare facilities in Ibadan, Nigeria, for bacteremia and malaria parasitemia. Methods Febrile patients underwent clinical diagnosis, malaria parasite testing, and blood culture. Bacteria from positive blood cultures were isolated and speciated using biochemical and serological methods, and Salmonella subtyping was performed by polymerase chain reaction. Antimicrobial susceptibility was tested by disk diffusion. Results A total of 682 patients were recruited between 16 June and 16 October 2017; 467 (68.5%) were <18 years of age. Bacterial pathogens were cultured from the blood of 117 (17.2%) patients, with Staphylococcus aureus (69 [59.0%]) and Salmonella enterica (34 [29.1%]) being the most common species recovered. Twenty-seven (79.4%) of the Salmonella isolates were serovar Typhi and the other 7 belonged to nontyphoidal Salmonella serovarieties. Thirty-four individuals were found to be coinfected with Plasmodium falciparum and bacteria. Five (14.7%) of these coinfections were with Salmonella, all in children aged <5 years. Antimicrobial susceptibility testing revealed that most of the Salmonella and Staphylococcus isolates were multidrug resistant. Conclusions The study demonstrates that bacteria were commonly recovered from febrile patients with or without malaria in this location. Focused and extended epidemiological studies are needed for the introduction of typhoid conjugate vaccines that have the potential to prevent a major cause of severe community-acquired febrile diseases in our locality.

scholarly journals Animal and Human Multidrug-Resistant, Cephalosporin-ResistantSalmonella Isolates Expressing a Plasmid-Mediated CMY-2 AmpC β-Lactamase

2000 ◽  
Vol 44 (10) ◽  
pp. 2777-2783 ◽  
Author(s):  
P. L. Winokur ◽  
A. Brueggemann ◽  
D. L. DeSalvo ◽  
L. Hoffmann ◽  
M. D. Apley ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Plasmid Dna ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Geographic Region ◽  
Chromosomal Dna ◽  
Important Food ◽  
Food Borne ◽  
Clonal Spread ◽  
Resistance Rates

ABSTRACT Salmonella spp. are important food-borne pathogens that are demonstrating increasing antimicrobial resistance rates in isolates obtained from food animals and humans. In this study, 10 multidrug-resistant, cephalosporin-resistant Salmonellaisolates from bovine, porcine, and human sources from a single geographic region were identified. All isolates demonstrated resistance to cephamycins and extended-spectrum cephalosporins as well as tetracycline, chloramphenicol, streptomycin, and sulfisoxazole. Molecular epidemiological analyses revealed eight distinct chromosomal DNA patterns, suggesting that clonal spread could not entirely explain the distribution of this antimicrobial resistance phenotype. However, all isolates encoded an AmpC-like β-lactamase, CMY-2. Eight isolates contained a large nonconjugative plasmid that could transformEscherichia coli. Transformants coexpressed cephalosporin, tetracycline, chloramphenicol, streptomycin, and sulfisoxazole resistances. Plasmid DNA revealed highly related restriction fragments though plasmids appeared to have undergone some evolution over time. Multidrug-resistant, cephalosporin-resistant Salmonellaspp. present significant therapeutic problems in animal and human health care and raise further questions about the association between antimicrobial resistance, antibiotic use in animals, and transfer of multidrug-resistant Salmonella spp. between animals and man.

scholarly journals Antibiotic Pipeline Coordinators

2018 ◽  
Vol 46 (S1) ◽  
pp. 25-31 ◽  
Author(s):  
Enrico Baraldi ◽  
Olof Lindahl ◽  
Miloje Savic ◽  
David Findlay ◽  
Christine Årdal
Keyword(s):  
Research And Development ◽  
World Health ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Priority List ◽  
Non Profit ◽  
Global Priority ◽  
The World ◽  
New Antibiotics ◽  
Health Organization

The World Health Organization (WHO) has published a global priority list of antibiotic-resistant bacteria to guide research and development (R&D) of new antibiotics. Every pathogen on this list requires R&D activity, but some are more attractive for private sector investments, as evidenced by the current antibacterial pipeline. A “pipeline coordinator” is a governmental/non-profit organization that closely tracks the antibacterial pipeline and actively supports R&D across all priority pathogens employing new financing tools.

scholarly journals Salmonella enterica Serovar Typhi Strains Isolated in Korea Containing a Multidrug Resistance Class 1 Integron

2003 ◽  
Vol 47 (6) ◽  
pp. 2006-2008 ◽  
Author(s):  
Hyunjoo Pai ◽  
Jeong-hum Byeon ◽  
Sunmi Yu ◽  
Bok Kwon Lee ◽  
Shukho Kim
Keyword(s):  
Multidrug Resistance ◽  
Resistance Genes ◽  
Salmonella Enterica ◽  
Multidrug Resistant ◽  
Conjugative Plasmid ◽  
The Novel ◽  
Class 1 Integron ◽  
Salmonella Enterica Serovar Typhi ◽  
Class 1 ◽  
Clonal Spread

ABSTRACT Six strains of Salmonella enterica serovar Typhi which were resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, streptomycin, tetracycline, and gentamicin were isolated in Korea. This multidrug resistance was transferred by a conjugative plasmid of about 50 kb. The plasmid harbored a class 1 integron, which included six resistance genes, aacA4b, catB8, aadA1, dfrA1, aac(6′)-IIa, and the novel blaP2, in that order. All of the isolates showed the same-size plasmids and the same ribotyping patterns, which suggests a clonal spread of these multidrug-resistant isolates.

Global priority pathogens: virulence, antimicrobial resistance and prospective treatment options

2020 ◽  
Vol 15 (8) ◽  
pp. 649-677 ◽  
Author(s):  
Juliana C de M Campos ◽  
Luis CM Antunes ◽  
Rosana BR Ferreira
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Salmonella Spp ◽  
Multidrug Resistant Bacteria ◽  
Major Threat ◽  
Global Priority ◽  
Resistant Strains ◽  
Therapeutic Alternatives ◽  
New Strategies

Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Salmonella spp. are part of a group of pathogens that pose a major threat to human health due to the emergence of multidrug-resistant strains. Moreover, these bacteria have several virulence factors that allow them to successfully colonize their hosts, such as toxins and the ability to produce biofilms, resulting in an urgent need to develop new strategies to fight these pathogens. In this review, we compile the most up-to-date information on the epidemiology, virulence and resistance of these clinically important microorganisms. Additionally, we address new therapeutic alternatives, with a focus on molecules with antivirulence activity, which are considered promising to combat multidrug-resistant bacteria.

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