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 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 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 Induction signals for vancomycin resistance encoded by the vanA gene cluster in Enterococcus faecium.

1996 ◽  
Vol 40 (7) ◽  
pp. 1645-1648 ◽  
Author(s):  
M H Lai ◽  
D R Kirsch
Keyword(s):  
Gene Cluster ◽  
Cyclic Peptide ◽  
Response Regulator ◽  
Polymyxin B ◽  
Vancomycin Resistance ◽  
Sensor Response ◽  
Peptide Antibiotics ◽  
Synthetic Compounds ◽  
Vana Gene ◽  
Two Component

The induction of vancomycin resistance in enterococci containing the vanA gene cluster is thought to be controlled by a two-component sensor-response regulator system encoded by vanR and vanS. Eight inducing compounds were identified by screening a panel of more than 6,800 antibiotics and synthetic compounds including the three tested glycopeptides (vancomycin, avoparcin, and ristocetin), two other cell wall biosynthesis inhibitors (moenomycin and bacitracin), two cyclic peptide antibiotics (antibiotic AO341 beta and polymyxin B), and a macrocyclic lactone antibiotic (moxidectin). Induction activity by structurally unrelated antibiotics suggests that the induction signal is not a structural feature of vancomycin.

scholarly journals The Biopesticide Paenibacillus popilliae Has a Vancomycin Resistance Gene Cluster Homologous to the Enterococcal VanA Vancomycin Resistance Gene Cluster

2000 ◽  
Vol 44 (3) ◽  
pp. 705-709 ◽  
Author(s):  
Robin Patel ◽  
Kerryl Piper ◽  
Franklin R. Cockerill ◽  
James M. Steckelberg ◽  
Allan A. Yousten
Keyword(s):  
Gene Cluster ◽  
Resistance Gene ◽  
Bacterial Resistance ◽  
Vancomycin Resistance ◽  
Amino Acid Sequences ◽  
Agricultural Practice ◽  
Human Pathogens ◽  
Resistance Gene Cluster ◽  
Genes Encoding ◽  
Vancomycin Resistant

ABSTRACT We have previously identified, in Paenibacillus popilliae, a 708-bp sequence which has homology to the sequence of the enterococcal vanA gene. We have performed further studies revealing five genes encoding homologues of VanY, VanZ, VanH, VanA, and VanX in P. popilliae. The predicted amino acid sequences are similar to those in VanA vancomycin-resistant enterococci: 61% identity for VanY, 21% for VanZ, 74% for VanH, 77% for VanA, and 79% for VanX. The genes in P. popilliae may have been a precursor to or have had ancestral genes in common with vancomycin resistance genes in enterococci. The use of P. popilliae biopesticidal preparations in agricultural practice may have an impact on bacterial resistance in human pathogens.

scholarly journals A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan, November to December 2013

2014 ◽  
Vol 19 (1) ◽  
Author(s):  
E Takashita ◽  
M Ejima ◽  
R Itoh ◽  
M Miura ◽  
A Ohnishi ◽  
...  
Keyword(s):  
Influenza A ◽  
Cross Resistance ◽  
Neuraminidase Inhibitors ◽  
Resistant Virus ◽  
Pdm09 Virus ◽  
Specimen Collection ◽  
Influenza A H1n1 ◽  
Clonal Spread ◽  
Epidemiological Link

Six influenza A(H1N1)pdm09 viruses were detected in Sapporo, Japan, between November and December 2013. All six viruses possessed an H275Y substitution in the neuraminidase protein, which confers cross-resistance to oseltamivir and peramivir. No epidemiological link among the six cases could be identified; none of them had received neuraminidase inhibitors before specimen collection. The haemagglutinin and neuraminidase genes of the six viruses were closely related to one another, suggesting clonal spread of a single resistant virus.

scholarly journals 159. Genomic Epidemiology of MRSA at Intake to a Large Inner-City Jail: Evidence for Community Transmission Networks?

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S13-S14 ◽  
Author(s):  
Kyle J Popovich ◽  
Evan S Snitkin ◽  
Stefan J Green ◽  
Alla Aroutcheva ◽  
Michael Schoeny ◽  
...  
Keyword(s):  
Cook County ◽  
Hiv Care ◽  
Transmission Networks ◽  
Genomic Epidemiology ◽  
High Prevalence ◽  
Community Transmission ◽  
Clonal Spread ◽  
Small Clusters ◽  
The Impact ◽  
Mrsa Colonization

Abstract Background USA300 is endemic in the community, with congregate settings potentially facilitating spread. The impact of community MRSA transmission networks on importation of MRSA into urban jails is unknown. We examined MRSA colonization isolates entering the jail and determined whether there are community transmission networks for MRSA that precede incarceration. Methods HIV-infected and HIV-negative males incarcerated at the Cook County Jail were enrolled within 72 hours of intake. Surveillance cultures (nares, throat, and groin) were collected to determine prevalence of MRSA colonization. A survey was administered to identify predictors of colonization. Whole-genome sequencing (WGS) and phylogenetic analysis were integrated with epidemiologic data to identify community transmission networks. Results A total of 800 males were enrolled (83% AA and 9% Hispanic); 58% were HIV-infected. The prevalence of MRSA colonization at intake was 19%. In multivariate analysis, methamphetamine use (METH), unstable housing, and prior jail incarceration were significant predictors of MRSA. Among HIV patients, injection drug use and HIV care at outpatient Clinic A that emphasize comprehensive care to the LGBTQ community were significant predictors of MRSA. Of the 31 (45%) patients with care at Clinic A, 14 had MRSA colonization. We sequenced 145 isolates from unique individuals, with 102 and 13 closely related to USA300 and USA500 reference genomes, respectively. USA300 strains from intake were diverse (median pairwise SNV distance = 109), with several small clusters noted. WGS revealed the high prevalence of MRSA in Clinic A was not due to clonal spread but rather an intermingling of distinct community transmission networks (strains were highly diverse; median pairwise SNV distance = 410). We did identify a 13-member community transmission network underlying spread of USA500 (figure). Members of this network were more likely to be HIV-infected (P < 0.004), MSM (P < 0.001), and METH (P < 0.001). Conclusion A high proportion of individuals enter jail already colonized with MRSA and colonization risk factors provide clues to community reservoirs for MRSA. WGS extended epidemiologic analysis and revealed community transmission networks that could be a potential focus for an intervention. Disclosures All authors: No reported disclosures.

scholarly journals Vancomycin-resistance gene cluster, vanC, in the gut microbiome of acute leukemia patients undergoing intensive chemotherapy

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0223890 ◽  
Author(s):  
Armin Rashidi ◽  
Zhigang Zhu ◽  
Thomas Kaiser ◽  
Dawn A. Manias ◽  
Shernan G. Holtan ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Gene Cluster ◽  
Resistance Gene ◽  
Gut Microbiome ◽  
Vancomycin Resistance ◽  
Intensive Chemotherapy ◽  
Resistance Gene Cluster

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.

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