scholarly journals Inter-species geographic signatures for tracing horizontal gene transfer and long-term persistence of carbapenem resistance

2021 ◽  
Author(s):  
Rauf Salamzade ◽  
Abigail L. Manson ◽  
Bruce J. Walker ◽  
Thea Brennan-Krohn ◽  
Colin J. Worby ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Genome Rearrangement ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Hospital Environment ◽  
Whole Genome Sequence ◽  
Diverse Range ◽  
Carbapenem Resistant ◽  
Genome Assemblies

Background: Carbapenem-resistant Enterobacterales (CRE) are an urgent global health threat. Inferring the dynamics of local CRE dissemination is currently limited by our inability to confidently trace the spread of resistance determinants to unrelated bacterial hosts. Whole genome sequence comparison is useful for identifying CRE clonal transmission and outbreaks, but high-frequency horizontal gene transfer (HGT) of carbapenem resistance genes and subsequent genome rearrangement complicate tracing the local persistence and mobilization of these genes across organisms. Methods: To overcome this limitation, we developed a new approach to identify recent HGT of large, near identical plasmid segments across species boundaries, which also allowed us to overcome technical challenges with genome assembly. We applied this to complete and near-complete genome assemblies to examine the local spread of CRE in a systematic, prospective collection of all CRE, as well as time- and species-matched carbapenem susceptible Enterobacterales, isolated from patients from four U.S. hospitals over nearly five years. Results: Our CRE collection comprised a diverse range of species, lineages and carbapenem resistance mechanisms, many of which were encoded on a variety of promiscuous plasmid types. We found and quantified rearrangement, persistence, and repeated transfer of plasmid segments, including those harboring carbapenemases, between organisms over multiple years. Some plasmid segments were found to be strongly associated with specific locales, thus representing geographic signatures that make it possible to trace recent and localized HGT events. Functional analysis of these signatures revealed genes commonly found in plasmids of nosocomial pathogens, such as functions required for plasmid retention and spread, as well survival against a variety of antibiotic and antiseptics common to the hospital environment. Conclusions: Collectively, the framework we developed provides a clearer, high resolution picture of the epidemiology of antibiotic resistance importation, spread, and persistence in patients and healthcare networks.

scholarly journals Identification of blaGIM-1 in Acinetobacter variabilis isolated from the hospital environment in Tamil Nadu, India

2019 ◽  
Author(s):  
Prasanth Manohar ◽  
Murugavel Ragavi ◽  
Ashby Augustine ◽  
Hrishikesh MV ◽  
Nachimuthu Ramesh
Keyword(s):  
Tamil Nadu ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Hospital Environment ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Hospital Environments ◽  
Surveillance Programs

AbstractBackgroundEmergence of carbapenem resistance mechanisms among Gram-negative bacteria is a worrisome health problem. Here, we focused on to identify the presence of carbapenem-resistant bacteria among the samples collected from hospital environments in Tamil Nadu.MethodsA total of 30 hospital environmental samples were collected between August 2017 and January 2018 from hospitals located in Chennai and Vellore such as lift switches, stair rails, switchboards, nursing desks, used nursing gloves, door handles, wheelchairs, touch screens, chairs and from pillars inside the hospitals.Results and discussionA total of 22 carbapenem-resistant Gram-negative bacteria were isolated that included Escherichia coli, Klebsiella sp., Enterobacter sp., Salmonella sp., Pseudomonas aeruginosa and Acinetobacter sp. Interestingly, blaGIM-1 was detected in Acinetobacter variabilis strain isolated in samples collected from hospitals. Unlike other studies, the identified GIM-1 was not plasmid encoded, and this is the first report for the presence of GIM-1 (German imipenemase) in India.ConclusionExtensive surveillance programs are necessary to trace the uncontrolled spread of carbapenem-resistance genes in order to reduce the rapid spread of resistance.

scholarly journals Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Michael J. Satlin ◽  
Liang Chen ◽  
Gopi Patel ◽  
Angela Gomez-Simmonds ◽  
Gregory Weston ◽  
...  
Keyword(s):  
New York ◽  
Empirical Therapy ◽  
Carbapenem Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Rapid Diagnostics ◽  
Multicenter Studies ◽  
Content Type ◽  
Medical Centers ◽  
Carbapenem Resistant

ABSTRACT Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.

scholarly journals Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
Na Huang ◽  
...  
Keyword(s):  
Lipid A ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Resistance Mechanisms ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Horizontal Spread

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

scholarly journals Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks

2017 ◽  
Vol 114 (5) ◽  
pp. 1135-1140 ◽  
Author(s):  
Gustavo C. Cerqueira ◽  
Ashlee M. Earl ◽  
Christoph M. Ernst ◽  
Yonatan H. Grad ◽  
John P. Dekker ◽  
...  
Keyword(s):  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Phylogeographic Structure ◽  
Aggressive Approach ◽  
Beta Lactamases ◽  
Carbapenem Resistant ◽  
Local Transmission ◽  
California Hospital ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
The Continuum

Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species. We found eight species exhibiting resistance, with the majority of our sample being the sequence type 258 (ST258) lineage ofKlebsiella pneumoniae. There was very little evidence of extensive hospital outbreaks, but a great deal of variation in resistance mechanisms and the genomic backgrounds carrying these mechanisms. Local transmission was evident in clear phylogeographic structure between the samples from the two coasts. The most common resistance mechanisms were KPC (K. pneumoniaecarbapenemases) beta-lactamases encoded byblaKPC2,blaKPC3, andblaKPC4, which were transferred between strains and species by seven distinct subgroups of the Tn4401element. We also found evidence for previously unrecognized resistance mechanisms that produced resistance when transformed into a susceptible genomic background. The extensive variation, together with evidence of transmission beyond limited clonal outbreaks, points to multiple unsampled transmission chains throughout the continuum of care, including asymptomatic carriage and transmission of CRE. This finding suggests that to control this threat, we need an aggressive approach to surveillance and isolation.

scholarly journals Predominance of Acinetobacter spp., Harboring the blaIMP Gene, Contaminating the Hospital Environment in a Tertiary Hospital in Mwanza, Tanzania: A Cross-Sectional Laboratory-Based Study

Pathogens ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 63
Author(s):  
Vitus Silago ◽  
Eveline C. Mruma ◽  
Betrand Msemwa ◽  
Conjester I. Mtemisika ◽  
Shukurani Phillip ◽  
...  
Keyword(s):  
Carbapenem Resistance ◽  
Tertiary Hospital ◽  
Hospital Environment ◽  
Pcr Assay ◽  
Cross Sectional ◽  
Middle Income ◽  
Carbapenem Resistant ◽  
Multiplex Pcr Assay ◽  
Genes Encoding ◽  
Acinetobacter Spp

Data on colonization and hospital contamination of carbapenem-resistant Gram-negative bacteria (CR-GNB) are limited in low- and middle-income countries. We designed this study to determine the prevalence and co-existence of carbapenemase genes among CR-GNB isolated from clinical, colonization, and hospital environmental samples at a tertiary hospital in Mwanza, Tanzania. The modified Hodge test (MHT), the combined disk test (CDT), and the double-disk synergy test (DDST) were used for the phenotypic detection of carbapenemases. A multiplex PCR assay was used to detect blaIMP and blaKPC, and a singleplex PCR assay was used to detect blaOXA-48. Data were analyzed by STATA version 13.0. Overall, 68.8% (44/64) of the CR-GNB had at least one phenotype by phenotypic methods, whereby 60.9% (39/64) were both CDT and DDST positive and 31.3% (20/64) were MHT positive. A total of 23/64 (35.9%) had at least one of the genes tested with the predominance of blaIMP (91.3%; 21/23). In addition, 47.7% (21/44) of the CR-GNB phenotypes had at least one gene. Around 47.8% (11/23) of the CR-GNB carried multiple genes encoding for carbapenem resistance, with the maximum co-existence of blaIMP/blaKPC/blaOXA-48 (45.5%; 5/11). The majority of carbapenem-resistant genes were detected in Acinetobacter spp. (82.6%; 19/23) and isolated from bed swabs (69.6%; 16/23). Acinetobacter spp. carrying the blaIMP gene predominantly contaminated the hospital environment. Therefore, we recommend routine decontamination of inanimate hospital surfaces, including patient beds.

scholarly journals Shared transcriptional control and disparate gain and loss of aphid parasitism genes and loci acquired via horizontal gene transfer

2018 ◽  
Author(s):  
Peter Thorpe ◽  
Carmen M. Escudero-Martinez ◽  
Peter J. A. Cock ◽  
D. Laetsch ◽  
Sebastian Eves-van den Akker ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Gene Duplication ◽  
Host Range ◽  
Genome Evolution ◽  
Transcriptional Control ◽  
Control Mechanism ◽  
Aphid Species ◽  
Gain And Loss ◽  
Genome Assemblies

AbstractBackgroundAphids are a diverse group of taxa that contain hundreds of agronomically important species, which vary in their host range and pathogenicity. However, the genome evolution underlying agriculturally important aphid traits is not well understood.ResultsWe generated highly-contiguous draft genome assemblies for two aphid species: the narrow host range Myzus cerasi, and the cereal specialist Rhopalosiphum padi. Using a de novo gene prediction pipeline on both these genome assemblies, and those of three related species (Acyrthosiphon pisum, D. noxia and M. persicae), we show that aphid genomes consistently encode similar gene numbers, and in the case of A. pisum, fewer and larger genes than previously reported. We compare gene content, gene duplication, synteny, horizontal gene transfer events, and putative effector repertoires between these five species to understand the genome evolution of globally important plant parasites.Aphid genomes show signs of relatively distant gene duplication, and substantial, relatively recent, gene birth, and are characterized by disparate gain and loss of genes acquired by horizontal gene transfer (HGT). Such HGT events account for approximately 1% of loci, and contribute to the protein-coding content of aphid species analysed. Putative effector repertoires, originating from duplicated loci, putative HGT events and other loci, have an unusual genomic organisation and evolutionary history. We identify a highly conserved effector-pair that is tightly genetically-linked in all aphid species. In R. padi, this effector pair is tightly transcriptionally-linked, and shares a transcriptional control mechanism with a subset of approximately 50 other putative effectors distributed across the genome.ConclusionsThis study extends our current knowledge on the evolution of aphid genomes and reveals evidence for a shared control mechanism, which underlies effector expression, and ultimately plant parasitism.

scholarly journals Carbapenem Resistance: Mechanisms and Drivers of Global Menace

2020 ◽  
Author(s):  
Bilal Aslam ◽  
Maria Rasool ◽  
Saima Muzammil ◽  
Abu Baker Siddique ◽  
Zeeshan Nawaz ◽  
...  
Keyword(s):  
Global Health ◽  
Protein Modification ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Health Concern ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Global Health Issue ◽  
Class I Integrons ◽  
Day By Day

The emergence of carbapenem-resistant bacterial pathogens is a significant and mounting health concern across the globe. At present, carbapenem resistance (CR) is considered as one of the most concerning resistance mechanisms and mainly found in gram-negative bacteria of the Enterobacteriaceae family. Although carbapenem resistance has been recognized in Enterobacteriaceae from last 20 years or so, recently it emerged as a global health issue as CR clonal dissemination of various Enterobacteriaceae members especially E. coli, and Klebsiella pneumoniae are reported from across the globe at an alarming rate. Phenotypically, carbapenems resistance is in due to the two key mechanisms, like structural mutation coupled with β-lactamase production and the ability of the pathogen to produce carbapenemases which ultimately hydrolyze the carbapenem. Additionally, penicillin-binding protein modification and efflux pumps are also responsible for the development of carbapenem resistance. Carbapenemases are classified into different classes which include Ambler classes A, B, and D. Several mobile genetic elements (MGEs) have their potential role in carbapenem resistance like Tn4401, Class I integrons, IncFIIK2, IncF1A, and IncI2. Taking together, resistance against carbapenems is continuously evolving and posing a significant health threat to the community. Variable mechanisms that are associated with carbapenem resistance, different MGEs, and supplementary mechanisms of antibiotic resistance in association with virulence factors are expanding day by day. Timely demonstration of this global health concern by using molecular tools, epidemiological investigations, and screening may permit the suitable measures to control this public health menace.

Modern View on Enterococcus faecalis and Enterococcus faecium Resistance Mechanisms to Antibiotics

2021 ◽  
Vol 65 (11-12) ◽  
pp. 38-48
Author(s):  
T. S. Komenkova ◽  
E. A. Zaitseva
Keyword(s):  
Clinical Practice ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Current Knowledge ◽  
Common Species ◽  
Resistance Mechanisms ◽  
Causative Agents ◽  
Level Resistance

Enterococci are currently becoming one of the major causative agents of various infectious diseases. Enterococcus faecalis and E.faecium are the most common species causing enterococcal infections. Both species exhibit natural low-level resistance to aminoglycosides, cephalosporins, quinolones, clindamycin, and co-trimoxazole. In addition, the peculiarities of their genome make it easy to acquire resistance to other antibiotics widely used in clinical practice, through mutations or by horizontal gene transfer. The review represents current knowledge about the mechanisms of enterococcal resistance to the most commonly used antibiotics.

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.

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