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      Molecular Mechanisms and Epidemiology of Carbapenem-Resistant Enterobacter cloacae Complex Isolated from Chinese Patients During 2004–2018

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          Abstract

          Background

          The emergence and spread of carbapenem-resistant Enterobacter cloacae complex (ECC) have posed a serious threat to human health worldwide. This study aimed to investigate the molecular mechanism of carbapenem resistance and its prevalence among ECC in China.

          Methods

          A total of 1314 ECC clinical isolates were collected from the First Affiliated Hospital of Wenzhou Medical University from 2004 to 2018. Sensitivity to antibiotics was determined using the agar dilution method. The production of carbapenemases and the prevalence of resistance-associated genes were investigated using PCR. The expression of outer membrane porin (OMP) genes ( ompC/ ompF) and cephalosporinase gene ampC was analyzed by quantitative real-time PCR. The effect of efflux pump mechanism on carbapenem resistance was tested. ECC was typed by multilocus sequence typing (MLST).

          Results

          In this study, 113 carbapenem-nonsusceptible ECC strains were identified. The prevalence rates of carbapenemase genes bla KPC-2 and bla NDM were 12.4% (14/113) and 17.7% (20/113), and that of the extended-spectrum β-lactamase (ESBL) genes bla CTX-M, bla TEM, and bla SHV were 28.3% (32/113), 27.4% (31/113), and 14.2% (16/113), respectively. Among 67 carbapenem-nonsusceptible ECC isolates producing non-carbapenemase, low expression of ompC/ompF and overexpression of ampC were found in 46 and 40 strains, respectively. In addition, the carbapenem resistance was related to the overexpression of the efflux pump in the study. Finally, the 113 carbapenem-nonsusceptible ECC strains were categorized into 39 different sequence types using MLST.

          Conclusion

          Carbapenem-nonsusceptible ECC strains producing non-carbapenemase were predominant. The low expression of OMP with the overexpression of cephalosporinase or production of ESBLs and overexpression of efflux pump might contribute to the resistance to carbapenem for carbapenem-nonsusceptible ECC strains producing non-carbapenemase. The bla NDM and bla KPC comprised the principal resistance mechanism of carbapenemase-producing ECC in the hospital, causing a threat to public health. Therefore, monitoring programs to prevent the emergence and further spread of antibiotic resistance are urgently needed.

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          Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India.

          Dongeun Yong, Mark Toleman, Christian G Giske … (2009)
          A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex. The isolate, Klebsiella pneumoniae 05-506, was shown to possess a metallo-beta-lactamase (MBL) but was negative for previously known MBL genes. Gene libraries and amplification of class 1 integrons revealed three resistance-conferring regions; the first contained bla(CMY-4) flanked by ISEcP1 and blc. The second region of 4.8 kb contained a complex class 1 integron with the gene cassettes arr-2, a new erythromycin esterase gene; ereC; aadA1; and cmlA7. An intact ISCR1 element was shown to be downstream from the qac/sul genes. The third region consisted of a new MBL gene, designated bla(NDM-1), flanked on one side by K. pneumoniae DNA and a truncated IS26 element on its other side. The last two regions lie adjacent to one another, and all three regions are found on a 180-kb region that is easily transferable to recipient strains and that confers resistance to all antibiotics except fluoroquinolones and colistin. NDM-1 shares very little identity with other MBLs, with the most similar MBLs being VIM-1/VIM-2, with which it has only 32.4% identity. As well as possessing unique residues near the active site, NDM-1 also has an additional insert between positions 162 and 166 not present in other MBLs. NDM-1 has a molecular mass of 28 kDa, is monomeric, and can hydrolyze all beta-lactams except aztreonam. Compared to VIM-2, NDM-1 displays tighter binding to most cephalosporins, in particular, cefuroxime, cefotaxime, and cephalothin (cefalotin), and also to the penicillins. NDM-1 does not bind to the carbapenems as tightly as IMP-1 or VIM-2 and turns over the carbapenems at a rate similar to that of VIM-2. In addition to K. pneumoniae 05-506, bla(NDM-1) was found on a 140-kb plasmid in an Escherichia coli strain isolated from the patient's feces, inferring the possibility of in vivo conjugation. The broad resistance carried on these plasmids is a further worrying development for India, which already has high levels of antibiotic resistance.
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            Enterobacter aerogenes and Enterobacter cloacae; versatile bacterial pathogens confronting antibiotic treatment

            Anne Davin-Regli, Jean-Marie Pagès (2015)
            Enterobacter aerogenes and E. cloacae have been reported as important opportunistic and multiresistant bacterial pathogens for humans during the last three decades in hospital wards. These Gram-negative bacteria have been largely described during several outbreaks of hospital-acquired infections in Europe and particularly in France. The dissemination of Enterobacter sp. is associated with the presence of redundant regulatory cascades that efficiently control the membrane permeability ensuring the bacterial protection and the expression of detoxifying enzymes involved in antibiotic degradation/inactivation. In addition, these bacterial species are able to acquire numerous genetic mobile elements that strongly contribute to antibiotic resistance. Moreover, this particular fitness help them to colonize several environments and hosts and rapidly and efficiently adapt their metabolism and physiology to external conditions and environmental stresses. Enterobacter is a versatile bacterium able to promptly respond to the antibiotic treatment in the colonized patient. The balance of the prevalence, E. aerogenes versus E. cloacae, in the reported hospital infections during the last period, questions about the horizontal transmission of mobile elements containing antibiotic resistance genes, e.g., the efficacy of the exchange of resistance genes Klebsiella pneumoniae to Enterobacter sp. It is also important to mention the possible role of antibiotic use in the treatment of bacterial infectious diseases in this E. aerogenes/E. cloacae evolution.
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              Phenotypic and Genotypic Characterization of Carbapenem-resistant Enterobacteriaceae: Data From a Longitudinal Large-scale CRE Study in China (2012–2016)

              Qi Wang, Xiaojuan Wang, Juan Wang … (2018)
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                Author and article information

                Journal
                Journal ID (nlm-ta): Infect Drug Resist
                Journal ID (iso-abbrev): Infect Drug Resist
                Journal ID (publisher-id): idr
                Journal ID (pmc): idr
                Title: Infection and Drug Resistance
                Publisher: Dove
                ISSN (Electronic): 1178-6973
                Publication date (Electronic): 07 September 2021
                Publication date Collection: 2021
                Volume: 14
                Pages: 3647-3658
                Affiliations
                [1 ]Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang Province, People’s Republic of China
                [2 ]School of Laboratory Medicine and Life Science, Wenzhou Medical University , Wenzhou, Zhejiang Province, People’s Republic of China
                Author notes
                Correspondence: Zhongyong Wang; Tieli Zhou Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang Province, People’s Republic of ChinaTel +86-577-5557-9725; +86-577-8668-9885 Email wangforever2000@163.com; wyztli@163.com
                Article
                Publisher ID: 327595
                DOI: 10.2147/IDR.S327595
                PMC ID: 8434891
                PubMed ID: 34522107
                SO-VID: d571a648-3813-4f8c-8246-1bd50b2c5772
                Copyright © © 2021 Liu et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 02 July 2021
                Date accepted : 02 September 2021
                Page count
                Figures: 2, Tables: 4, References: 43, Pages: 12
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: carbapenemase,carbapenem-resistant mechanism,enterobacter cloacae complex,epidemiology,non-carbapenemase
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: carbapenemase, carbapenem-resistant mechanism, enterobacter cloacae complex, epidemiology, non-carbapenemase

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