scholarly journals Characterization of IncHI1B Plasmids Encoding Efflux Pump TmexCD2-ToprJ2 in Carbapenem-Resistant Klebsiella variicola, Klebsiella quasipneumoniae, and Klebsiella michiganensis Strains

2021 ◽  
Vol 12 ◽  
Author(s):  
Yujiao Wang ◽  
Bo Zhu ◽  
Min Liu ◽  
Xiutao Dong ◽  
Jianping Ma ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Health Concern ◽  
Close Monitoring ◽  
Carbapenem Resistant ◽  
Resistance Nodulation Division ◽  
Tertiary Hospitals ◽  
Severe Infections

Tigecycline serves as one of the last-resort antibiotics to treat severe infections caused by carbapenem-resistant Enterobacterales. Recently, a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, TmexCD1-ToprJ1, and its variants, TmexCD2-ToprJ2 and TmexCD3-ToprJ3, encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three TmexCD2-ToprJ2-harboring Klebsiella species strains, collected from two teaching tertiary hospitals in China, including one K. quasipneumoniae, one K. variicola, and one K. michiganensis. The three strains were characterized by antimicrobial susceptibility testing (AST), conjugation assay, WGS, and bioinformatics analysis. AST showed that K. variicola and K. quasipneumoniae strains were resistant to tigecycline with MIC values of 4μg/ml, whereas the K. michiganensis was susceptible to tigecycline with an MIC value of 1μg/ml. The TmexCD2-ToprJ2 clusters were located on three similar IncHI1B plasmids, of which two co-harbored the metallo-β-lactamase gene blaNDM-1. Conjugation experiments showed that all three plasmids were capable of self-transfer via conjugation. Our results showed, for the first time, that this novel plasmid-mediated tigecycline resistance mechanism TmexCD2-ToprJ2 has spread into different Klebsiella species, and clinical susceptibility testing may fail to detect. The co-occurrence of blaNDM-1 and TmexCD2-ToprJ2 in the same plasmid is of particular public health concern as the convergence of “mosaic” plasmids can confer both tigecycline and carbapenem resistance. Its further spread into other clinical high-risk Klebsiella clones will likely exacerbate the antimicrobial resistance crisis. A close monitoring of the dissemination of TmexCD-ToprJ encoding resistance should be considered.

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 Emergence of carbapenem-resistant ST131 Escherichia coli carrying blaOXA-244 in Germany, 2019 to 2020

2020 ◽  
Vol 25 (46) ◽  
Author(s):  
Sybille Welker ◽  
Sébastien Boutin ◽  
Thomas Miethke ◽  
Klaus Heeg ◽  
Dennis Nurjadi
Keyword(s):  
Escherichia Coli ◽  
Carbapenem Resistance ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Public Health Concern ◽  
Gram Negative ◽  
E Coli ◽  
Carbapenem Resistant ◽  
South West ◽  
Tertiary Hospitals

The dissemination of carbapenem-producing Gram-negative bacteria is a major public health concern. We report the first detection of OXA-244-producing ST131 O16:H5 Escherichia coli in three patients from two tertiary hospitals in the south-west of Germany. OXA-244 is emerging in Europe. Because of detection challenges, OXA-244-producing E. coli may be under-reported. The emergence of carbapenem resistance in a globally circulating high-risk clone, such as ST131 E. coli is of clinical relevance and should be monitored closely.

Systematic surveillance and meta-analysis on the prevalence of Metallo-β-Lactamase producers among carbapenem resistant clinical isolates in Pakistan

2020 ◽  
Author(s):  
Noor ul Ain ◽  
Samyyia Abrar ◽  
Rehan Ahmad Khan ◽  
Abdul Hannan ◽  
Namrah Imran ◽  
...  
Keyword(s):  
Infection Control ◽  
Meta Analysis ◽  
Carbapenem Resistance ◽  
Epidemiological Surveillance ◽  
Health Concern ◽  
New Delhi ◽  
Significant Heterogeneity ◽  
Carbapenem Resistant ◽  
Geographical Regions ◽  
Clinically Significant

Abstract Background: Rapid emergence of carbapenem resistance (CR) is a health concern of pertinent importance. Epidemiological surveillance of CR at global and indigenous level (Pakistan) can help to improve infection control strategy and establish pharmacovigilance programs. This study evaluate the prevalence of clinically significant CR isolates, and its genetic variant distribution among different geographical regions of Pakistan. Methods: A meta-analysis was conducted to present the current rate of CR infections and prevalence of Metallo-β-lactamases (MBLs). The proposed subject was researched using robustic electronic databases a) PubMed b) PubMed Central® (PMC), and c) Google Scholar to identify the available literature. Thereafter, relevant data was extracted and statistical analysis was performed using STATA version 14. Result: A total of 110 relevant studies were identified with 19 meeting the inclusion criteria for the meta-analysis of CR, while 22 for MBLs. Pooled rate for carbapenem resistance was determined to be 0.28 (95% CI: 0.26-0.31) with overall significant heterogeneity (I 2 =99.61%, p<0.001) and significant estimated score ES=0 (Z=22.65, p<0.001). In case of Pakistan, the overall pooled proportion of MBL producers was 0.34 (95% CI: 0.29-0.39) with overall heterogeneity significance (I 2 =99.62%, p<0.001) and respective significant ES=0 (Z=13.17, p<0.001). Conclusively, diverse variants of carbapenemases (VIM, IMP, NDM, KPC, GIM, SIM) along with other co-existing β-lactamase variants (OXA, TEM, SHV, CTX-M) have been reported across the country. However, New Delhi Metallo-β-lactamase (NDM)-variants were reported in predominant literature. Conclusion: The prevalence of CR isolates in Pakistan is alarming, associated with MBL production primarily evident from the studies. The study emphasizes the need for regular surveillance, pharmacovigilance and antibiotic stewardship programs to ensure the availability of data to the authorities for preemptive measures of infection control.

scholarly journals Molecular characteristics of carbapenem-resistant Acinetobacter spp. from clinical infection samples and fecal survey samples in Southern China

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Si Li ◽  
Xiaonv Duan ◽  
Yuan Peng ◽  
Yongyu Rui
Keyword(s):  
Efflux Pump ◽  
Southern China ◽  
Variable Region ◽  
Carbapenem Resistance ◽  
Resistant Bacteria ◽  
Molecular Characteristics ◽  
Clinical Infection ◽  
High Genetic Diversity ◽  
Carbapenem Resistant ◽  
Opportunistic Bacteria

Abstract Background Carbapenem resistance among Acinetobacter species has become a life-threatening problem. As a last resort in the treatment of gram-negative bacteria infection, resistance to colistin is also a serious problem. The aim of study was to analyze the mechanism of resistance and perform genotyping of carbapenem-resistant Acinetobacter from clinical infection and fecal survey samples in Southern China. Methods One hundred seventy and 74 carbapenem-resistant Acinetobacter were isolated from clinical infection samples and fecal survey samples, respectively. We detected the related genes, including carbapenemase genes (blaKPC, blaIMP, blaSPM, blaVIM, blaNDM, blaOXA-23-like, blaOXA-24/40-like, blaOXA-51-like, and blaOXA-58-like), colistin resistance-related genes (mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5), a porin gene (carO), efflux pump genes (adeA, adeB, adeC, adeI, adeJ, and adeK), mobile genetic element genes (intI1, intI2, intI3, tnpU, tnp513, IS26, ISAba1, and ISAba125), and the integron variable region. Genotyping was analyzed by enterobacterial repetitive intergenic consensus (ERIC)-PCR and dendrogram cluster analysis. Results Among the 244 carbapenem-resistant Acinetobacter, the common carbapenemase-positive genes included the following: blaOXA-51-like, 183 (75.00%); blaOXA-23-like, 174 (71.30%); blaNDM-1, 57 (23.40%); and blaOXA-58-like, 30 (12.30%). The coexistence of mcr-1 and blaNDM-1 in five strains of A. junii was found for the first time. Eleven distinct carO gene variants were detected in 164 (67.20%) strains, and ten novel variants, which shared 92–99% identity with sequences in the Genbank database, were first reported. Efflux system genes were present in approximately 70% of the isolates; adeABC and adeIJK were observed in 76.23 and 72.13%, respectively. Class 1 integrons were detected in 180 (73.80%) strains and revealed that four gene cassette arrays contained 11 distinct genes. The genotyping by ERIC-PCR demonstrated a high genetic diversity of non-baumannii Acinetobacter, and greater than 90% similarity to A. baumannii. Conclusions The blaNDM-1 gene was identified in up to 77% of the carbapenem-resistant Acinetobacter isolated from fecal survey samples, indicating that the gut might be a reservoir of resistant opportunistic bacteria. Intestinal bacteria can be transmitted through the fecal-hand, which is a clinical threat, thus, the monitoring of carbapenem-resistant bacteria from inpatients’ feces should be improved, especially for patients who have been using antibiotics for a long time.

scholarly journals Molecular Epidemiology of Emerging Carbapenem Resistance inAcinetobacter nosocomialisandAcinetobacter pittiiin Taiwan, 2010 to 2014

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Feng-Jui Chen ◽  
Wei-Cheng Huang ◽  
Yu-Chieh Liao ◽  
Hui-Ying Wang ◽  
Jui-Fen Lai ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Species Identification ◽  
Carbapenem Resistance ◽  
Close Monitoring ◽  
Aminoglycoside Resistance ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Acinetobacter Pittii ◽  
Aminoglycoside Resistance Genes ◽  
Genetic Structures

ABSTRACTThis study investigated the molecular epidemiology of carbapenem-resistantAcinetobacter nosocomialisandAcinetobacter pittii(ANAP). Clinical isolates ofAcinetobacterspp. collected by the biennial nationwide Taiwan Surveillance of Antimicrobial Resistance program from 2010 to 2014 were subjected to species identification, antimicrobial susceptibility testing, and PCR for detection of carbapenemase genes. Whole-genome sequencing or PCR mapping was performed to study the genetic surroundings of the carbapenemase genes. Among 1,041Acinetobacterisolates, the proportion of ANAP increased from 11% in 2010 to 22% in 2014. The rate of carbapenem resistance in these isolates increased from 7.5% (3/40) to 22% (14/64), with a concomitant increase in their resistance to other antibiotics. TheblaOXA-72andblaOXA-58genes were highly prevalent in carbapenem-resistant ANAP. Various genetic structures were found upstream ofblaOXA-58in different plasmids. Among the plasmids found to containblaOXA-72flanked by XerC/XerD, pAB-NCGM253-like was identified in 8 of 10 isolates. Conjugations of plasmids carryingblaOXA-72orblaOXA-58toA. baumanniiwere successful. In addition, three isolates with chromosome-locatedblaOXA-23embedded in AbGRI1-type structure with disruption of genes other thancomMwere detected. Two highly similar plasmids carrying class I integron containingblaIMP-1and aminoglycoside resistance genes were also found. The universal presence ofblaOXA-272/213-likeonA. pittiichromosomes and their lack of contribution to carbapenem resistance indicate its potential to be a marker for species identification. The increase of ANAP, along with their diverse mechanisms of carbapenem resistance, may herald their further spread and warrants close monitoring.

Carbapenem-resistantAcinetobacter baumannii: diversity of resistant mechanisms and risk factors for infection

2011 ◽  
Vol 140 (1) ◽  
pp. 137-145 ◽  
Author(s):  
Y. J. KIM ◽  
S. I. KIM ◽  
Y. R. KIM ◽  
K. W. HONG ◽  
S. H. WIE ◽  
...  
Keyword(s):  
Risk Factors ◽  
Efflux Pump ◽  
Clinical Epidemiology ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Apache Ii Score ◽  
Mechanisms Of Resistance ◽  
High Apache ◽  
Carbapenem Resistant ◽  
Clonal Spread

SUMMARYCarbapenem-resistantAcinetobacter baumannii(CRAB) are an increasing infectious threat in hospitals. We investigated the clinical epidemiology of CRAB infectionsvs. colonization in patients, and examined the mechanisms of resistance associated with elevated minimum inhibitory concentrations (MICs) for carbapenems. From January to June 2009, 75 CRAB strains were collected. CRAB infection was significantly associated with malignancy and a high APACHE II score. The most dominant resistance mechanism was ISAba1preceding OXA-51, producing strains with overexpression of efflux pump. Strains carryingblaOXA-23-like enzymes had higher carbapenem MICs than those carryingblaOXA-51-like enzymes; however, the presence of multiple mechanisms did not result in increased resistance to carbapenems. There was no difference in the resistance mechanisms in strains from infected and colonized patients. The majority of strains were genetically diverse by DNA macrorestriction although there was evidence of clonal spread of four clusters of strains in patients.

scholarly journals Plasmidome analysis of carbapenem-resistant Enterobacteriaceae isolated in Vietnam

2020 ◽  
Author(s):  
Aki Hirabayashi ◽  
Koji Yahara ◽  
Satomi Mitsuhashi ◽  
So Nakagawa ◽  
Tadashi Imanishi ◽  
...  
Keyword(s):  
Carbapenem Resistance ◽  
Genomic Epidemiology ◽  
Carbapenem Resistant ◽  
Oxford Nanopore ◽  
Carbapenemase Gene ◽  
Long Read ◽  
Severe Infections ◽  
Oxford Nanopore Technologies ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem-resistant Enterobacteriaceae (CRE) represent a serious threat to public health due to limited management of severe infections and high mortality. The rate of resistance of Enterobacteriaceae isolates to major antimicrobials, including carbapenems, is much higher in Vietnam than in Western countries, but the reasons remain unknown due to the lack of genomic epidemiology research. A previous study suggested that carbapenem resistance genes, such as the carbapenemase gene bla NDM-1 , spread via plasmids among Enterobacteriaceae in Vietnam. In this study, we performed detection and molecular characterization of bla NDM-1 -carrying plasmids in CRE isolated in Vietnam, and identified several possible cases of horizontal transfer of plasmids both within and among species of bacteria. Twenty-five carbapenem-resistant isolates from Enterobacteriaceae clinically isolated in a reference medical institution in Hanoi were sequenced on Illumina short-read sequencers, and 12 isolates harboring bla NDM-1 were sequenced on an Oxford Nanopore Technologies long-read sequencer to obtain complete plasmid sequences. Most of the plasmids co-carried genes conferring resistance to clinically relevant antimicrobials, including third-generation cephalosporins, aminoglycosides, and fluoroquinolones, in addition to bla NDM-1 , leading to multidrug resistance of their bacterial hosts. These results provide insight into the genetic basis of CRE in Vietnam, and could help control nosocomial infections.

scholarly journals Prevalence and mechanisms of carbapenem resistance  among  Klebsiella aerogenes  in a tertiary hospital in China

2020 ◽  
Author(s):  
Luxiang Liu ◽  
Jingjing Quan ◽  
Dongdong Zhao ◽  
Weichao Liao ◽  
Jiaojian Lv ◽  
...  
Keyword(s):  
Intensive Care ◽  
Efflux Pump ◽  
Carbapenem Resistance ◽  
Clonal Diversity ◽  
Tertiary Hospital ◽  
Molecular Characteristics ◽  
Klebsiella Aerogenes ◽  
Carbapenem Resistant ◽  
Efflux Pump Inhibition ◽  
Clonal Spread

Abstract Background: Klebsiella aerogenes has emerged as one of the most important nosocomial pathogens for patients in intensive care units (ICU) in recent years. This study aims to evaluated the prevalence and molecular characteristics of clinical carbapenem-resistant K. aerogenes (CRKA) isolates in a tertiary hospital in China.Results: Twenty CRKA were identified among all the isolates, with the rate of 5.5% (20/364). Six CRKA isolates produced KPC-2 and 1 CRKA isolate produced NDM-1. PFGE and MLST indicated that the 20 CRKA strains were clonal diversity. All the bla KPC-2 gene and bla NDM-1 gene were located on plasmids and all the plasmids with bla KPC-2 and bla NDM-1 genes could successfully transferred to EC600 or J53. Twelve of 13 CRKA strains without any carbapenemase genes were positive for efflux pump inhibition test.Conclusion: Overall, the prevalence of CRKA in the tertiary hospital in Zhejiang Province of China is 5.5%. Only 35% of CRKA produce carbapenemase and efflux pumps might play an important role in the carbapenem resistance of K. aerogenes. It is necessary to strengthen the surveillance of carbapenem resistance in the hospital to prevent the horizontal and clonal spread of CRKA.

scholarly journals Insights into the Resistome and Phylogenomics of a ST195 Multidrug-Resistant Acinetobacter baumannii Clinical Isolate from the Czech Republic

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1079
Author(s):  
Patrik Mlynarcik ◽  
Monika Dolejska ◽  
Iva Vagnerova ◽  
Jana Petrzelova ◽  
Iva Sukkar ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Isolate ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Clinical Settings ◽  
Sequencing Analysis ◽  
Pump System ◽  
The Czech Republic

Increasing antimicrobial resistance in nosocomial pathogens, such as Acinetobacter baumannii, is becoming a serious threat to public health. It is necessary to detect β-lactamase-producing microorganisms in clinical settings to be able to control the spread of carbapenem resistance. This study was conducted to evaluate the presence of β-lactamases in a selected clinical isolate of A. baumannii of ST2P/ST195Ox and to characterize possible enzymes, as well as its β-lactam resistome, using PCR and whole-genome sequencing analysis. PCR and sequencing confirmed that the isolate harbored five bla gene alleles, namely, blaADC-73, blaTEM-1, blaOXA-23, blaOXA-58 and blaOXA-66, as well as aminoglycosides, macrolides, sulfonamides and tetracyclines resistance determinants, which were either chromosomally and/or plasmid located. Furthermore, a gene order comparison using MAUVE alignment showed multiple changes compared with the clinical isolate of Malaysian A. baumannii AC30 genome and 76 regions with high homology. This study suggests that resistance to β-lactams in this A. baumannii isolate is mainly due to an overproduction of β-lactamases in combination with other resistance mechanism (efflux pump system).

scholarly journals Characterizing clinical carbapenem-resistant Klebsiella pneumoniae  phenotypes and genomic information reveals its molecular epidemiology

2019 ◽  
Author(s):  
Xiaoling Yu ◽  
Wen Zhang ◽  
Zhiping Zhao ◽  
Chengsong Ye ◽  
Shuyan Zhou ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Pathogenic Bacteria ◽  
Efflux Pump ◽  
Carbapenem Resistance ◽  
Snp Markers ◽  
Nucleotide Polymorphisms ◽  
Phenotypic Resistance ◽  
Carbapenem Resistant ◽  
Oxford Nanopore ◽  
Long Read

Abstract The enhancing incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP)-mediated infections in Mengchao Hepatobiliary Hospital of Fujian Medical University in 2017 promoted this investigation to study gene phenotypes and resistance genes of emergence regarding the CRKP strains. In current study, seven inpatients are enrolled in the hospital with complete treatments. The carbapenem-resistant K. pneumoniae whole genome is sequenced using MiSeq short-read and Oxford Nanopore long-read sequencing technology. Prophages are identified to assess genetic diversity within CRKP genomes. The investigation encompassed eight CRKP strains that collected from the patients enrolled as well as the environment, which illustrate that bla KPC-2 is responsible for phenotypic resistance in six CRKP strains that K . pneumoniae sequence type (ST-11) is inferred. The plasmid with IncR, ColRNAI and pMLST type with IncF[F33:A-:B-] co-exist in all ST-11 with KPC-2-producing CRKP strains. Along with carbapenemases, all K. pneumoniae strains harbor two or three extended spectrum β-lactamase (ESBL)-producing genes. F osA gene is detected amongst all the CRKP strains. The oqxA and oqxB expressions in CRKP strains may lead to carbapenem resistance since antimicrobials are expelled from pathogenic bacteria by efflux pump. The single nucleotide polymorphisms (SNP) markers are indicated and validated among all CRKP strains, providing valuable clues for distinguishing carbapenem-resistant strains from conventional K. pneumoniae .

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