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 Characterization of resistance mechanisms of Enterobacter cloacae Complex Co-resistant to Carbapenem and Colistin

2020 ◽  
Author(s):  
Tieli Zhou ◽  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Lipid A ◽  
Efflux Pump ◽  
Medical Center ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Colistin Resistance ◽  
Carbapenemase Gene

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.Methods: Nineteen ECC isolates co-resistant to carbapenems and colistin were collected from a regional medical center in China. Carbapenemase gene, extended-spectrum β-lactamase gene, AmpC cephalosporinase gene ampC, mcr series genes, and ecr gene were detected by PCR. Expression levels of outer membrane protein OmpC/OmpF and efflux pump protein AcrA/AcrB were investigated. And the structural modification of lipid A of 19 ECC strains was analyzed.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). And the mechanism of colistin resistance is increaseing expression of acrA in the efflux pump AcrAB-TolC alone (5 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 Characterization of resistance mechanisms of Enterobacter cloacae Complex Co-resistant to Carbapenem and Colistin

2021 ◽  
Author(s):  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
Na Huang ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Lipid A ◽  
Efflux Pump ◽  
Medical Center ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Colistin Resistance ◽  
Carbapenemase Gene

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. Methods: Nineteen ECC isolates co-resistant to carbapenems and colistin were collected from a regional medical center in China. Carbapenemase gene, extended-spectrum β-lactamase gene, AmpC cephalosporinase gene ampC, mcr series genes, and ecr gene were detected by PCR. Genetic clusters of based on hsp60 sequence analysis were performed. Expression levels of outer membrane protein OmpC/OmpF and efflux pump protein AcrA/AcrB were investigated. And the structural modification of lipid A of 19 ECC strains was analyzed. 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 increaseing expression of acrA in the efflux pump AcrAB-TolC alone (5 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 Antimicrobial Resistance Mechanisms and Virulence of Colistin- and Carbapenem-Resistant Acinetobacter baumannii Isolated from a Teaching Hospital in Taiwan

2021 ◽  
Vol 9 (6) ◽  
pp. 1295
Author(s):  
Noor Andryan Ilsan ◽  
Yuarn-Jang Lee ◽  
Shu-Chen Kuo ◽  
I-Hui Lee ◽  
Tzu-Wen Huang
Keyword(s):  
Acinetobacter Baumannii ◽  
Teaching Hospital ◽  
Lipid A ◽  
Signal Transduction Pathway ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Significant Difference

Acinetobacter baumannii, a Gram-negative bacterium, is an important nosocomial pathogen. Colistin-resistant A. baumannii is becoming a new concern, since colistin is one of the last-line antibiotics for infections by carbapenem-resistant A. baumannii. From 452 carbapenem-resistant isolates collected in a teaching hospital in Taipei, Taiwan, we identified seven that were resistant to colistin. Carbapenem resistance in these isolates is attributed to the presence of carbapenemase gene blaOXA-23 in their genomes. Colistin resistance is presumably conferred by mutations in the sensor kinase domain of PmrB found in these isolates, which are known to result in modification of colistin target lipid A via the PmrB–PmrA–PmrC signal transduction pathway. Overexpression of pmrC, eptA, and naxD was observed in all seven isolates. Colistin resistance mediated by pmrB mutations has never been reported in Taiwan. One of the seven isolates contained three mutations in lpxD and exhibited an altered lipopolysaccharide profile, which may contribute to its colistin resistance. No significant difference in growth rates was observed between the isolates and the reference strain, suggesting no fitness cost of colistin resistance. Biofilm formation abilities of the isolates were lower than that of the reference. Interestingly, one of the isolates was heteroresistant to colistin. Four of the isolates were significantly more virulent to wax moth larvae than the reference.

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 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 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 AmpC β-Lactamases

2009 ◽  
Vol 22 (1) ◽  
pp. 161-182 ◽  
Author(s):  
George A. Jacoby
Keyword(s):  
Broad Spectrum ◽  
Efflux Pump ◽  
Clinical Laboratory ◽  
Resistance Mechanism ◽  
Enterobacter Aerogenes ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Outer Membrane Porin ◽  
The World ◽  
Plasmid Genes

SUMMARY AmpC β-lactamases are clinically important cephalosporinases encoded on the chromosomes of many of the Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactamase inhibitor-β-lactam combinations. In many bacteria, AmpC enzymes are inducible and can be expressed at high levels by mutation. Overexpression confers resistance to broad-spectrum cephalosporins including cefotaxime, ceftazidime, and ceftriaxone and is a problem especially in infections due to Enterobacter aerogenes and Enterobacter cloacae, where an isolate initially susceptible to these agents may become resistant upon therapy. Transmissible plasmids have acquired genes for AmpC enzymes, which consequently can now appear in bacteria lacking or poorly expressing a chromosomal blaAmpC gene, such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Resistance due to plasmid-mediated AmpC enzymes is less common than extended-spectrum β-lactamase production in most parts of the world but may be both harder to detect and broader in spectrum. AmpC enzymes encoded by both chromosomal and plasmid genes are also evolving to hydrolyze broad-spectrum cephalosporins more efficiently. Techniques to identify AmpC β-lactamase-producing isolates are available but are still evolving and are not yet optimized for the clinical laboratory, which probably now underestimates this resistance mechanism. Carbapenems can usually be used to treat infections due to AmpC-producing bacteria, but carbapenem resistance can arise in some organisms by mutations that reduce influx (outer membrane porin loss) or enhance efflux (efflux pump activation).

scholarly journals Role of efflux pump and OprD porin expression in carbapenem resistance of Pseudomonas aeruginosa clinical isolates

2018 ◽  
Vol 12 (01) ◽  
pp. 001-008 ◽  
Author(s):  
Tuba Muderris ◽  
Rıza Durmaz ◽  
Birsen Ozdem ◽  
Tuba Dal ◽  
Ozlem Unaldı ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Carbapenem Resistance ◽  
High Sensitivity ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Clonal Relationship ◽  
Pfge Typing ◽  
Reverse Transcription Pcr ◽  
Carbapenem Resistant ◽  
Relationship Of

Introduction: In recent years, the prevalence of multidrug-resistant P. aeruginosa has remarkably increased. Thus, we wanted to investigate the carbapenem resistance mechanisms and clonal relationship among 80 carbapenem-resistant P. aeruginosa strains. Methodology: Carbapenemase production was detected using the Modified Hodge Test (MHT), EDTA combined disc method (ECD), and PCR. Expression levels of efflux and porin genes were mesured by real-time reverse transcription PCR. Clonal relationship of the isolates was investigated by pulsed-field gel electrophoresis (PFGE). Results: Carbapenemase production was detected in 7.5% of the isolates with MHT/ECD tests and in 11.3% of the isolates with PCR. Although the specificity of MHT/ECD was high, the sensitivitivity was low. oprD downregulation and mexB, mexY, and mexD overexpression were demonstrated in 55%, 16.3%, 2.5%, and 2.5% of the isolates, respectively. Multiple carbapenem resistance mechanisms were found in nearly a quarter of the isolates. PFGE typing of the 80 P. aeruginosa isolates yielded 61 different patterns. A total of 29 isolates (36.3%) were classified in 10 clusters, containing 2 to 7 strains. We could not find a strict relationship between PFGE profile and carbapenem resistance mechanisms. Conclusions: Although oprD downregulation and MexAB-OprM overexpression were the most common mechanisms, carbapenem resistance was associated with multiple mechanisms in the study. MHT/ECD tests should not be used alone for investigation of carbapenemase production in P. aeruginosa. Rapid tests with high sensitivity and specificity should be developed for the detection of carbapenemase production in P. aeruginosa.

scholarly journals Characterization of an Enterobacter cloacae Strain Producing both KPC and NDM Carbapenemases by Whole-Genome Sequencing

2015 ◽  
Vol 59 (10) ◽  
pp. 6625-6628 ◽  
Author(s):  
Wenjing Wu ◽  
Yu Feng ◽  
Alessandra Carattoli ◽  
Zhiyong Zong
Keyword(s):  
Whole Genome Sequencing ◽  
Bloodstream Infection ◽  
Genome Sequencing ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Whole Genome ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACTA carbapenem-resistantEnterobacter cloacaestrain, WCHECl-14653, causing a fatal bloodstream infection, was characterized by genome sequencing and conjugation experiments. The strain carried two carbapenemase genes,blaNDM-1andblaKPC-2, on separate IncF plasmids. The coexistence ofblaNDM-1andblaKPC-2conferred slightly higher-level carbapenem resistance compared with that ofblaNDM-1orblaKPC-2alone, and the coexistence of two IncF plasmids may generate new platforms for spreading carbapenemase genes.

scholarly journals Carbapenem Resistance Mechanisms in Pseudomonas aeruginosa Clinical Isolates

2001 ◽  
Vol 45 (2) ◽  
pp. 480-484 ◽  
Author(s):  
Hyunjoo Pai ◽  
Jong-Won Kim ◽  
Jungmin Kim ◽  
Ji Hyang Lee ◽  
Kang Won Choe ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Efflux System ◽  
Clinical Strains ◽  
Carbapenem Resistant

ABSTRACT In order to define the contributions of the mechanisms for carbapenem resistance in clinical strains of Pseudomonas aeruginosa, we investigated the presence of OprD, the expressions of the MexAB-OprM and MexEF-OprN systems, and the production of the β-lactamases for 44 clinical strains. All of the carbapenem-resistant isolates showed the loss of or decreased levels of OprD. Three strains overexpressed the MexAB-OprM efflux system by carrying mutations inmexR. These three strains had the amino acid substitution in MexR protein, Arg (CGG) → Gln (CAG), at the position of amino acid 70. None of the isolates, however, expressed the MexEF-OprN efflux system. For the characterization of β-lactamases, at least 13 isolates were the depressed mutants, and 12 strains produced secondary β-lactamases. Based on the above resistance mechanisms, the MICs of carbapenem for the isolates were analyzed. The MICs of carbapenem were mostly determined by the expression of OprD. The MICs of meropenem were two- to four-fold increased for the isolates which overexpressed MexAB-OprM in the background of OprD loss. However, the elevated MICs of meropenem for some individual isolates could not be explained. These findings suggested that other resistance mechanisms would play a role in meropenem resistance in clinical isolates of P. aeruginosa.

Sign in / Sign up

Export Citation Format

Share Document