3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Presence of Mobile Tigecycline Resistance Gene tet(X4) in Clinical Klebsiella pneumoniae

      brief-report

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          ABSTRACT

          The recently emerged plasmid-mediated tigecycline resistance gene tet(X4) has mainly been detected in Escherichia coli but never in Klebsiella pneumoniae. Herein, we identified a clinical K. pneumoniae isolate that harbored the tet(X4) gene located on a non-self-transferable IncFII-type plasmid, which could be cotransferred with a conjugative plasmid to E. coli C600. The extending of bacterial species carrying tet(X4) suggested the increasing risk of spreading mobile tigecycline resistance genes among important pathogens in clinical settings.

          IMPORTANCE Tigecycline, the first member of glycylcycline class antibiotic, is often considered one of the effective antibiotics against multidrug-resistant (MDR) infections. However, the emergence and wide distribution of two novel plasmid-mediated tigecycline resistance genes, tet(X3) and tet(X4), pose a great threat to the clinical use of tigecycline. The newly tet(X) variants have been identified from multiple different bacterial species, but the tet(X) variant in the Klebsiella pneumoniae strain has been reported only once before. In this study, we identified a clinical K. pneumoniae isolate that harbored a non-self-transferable tet(X4)-carrying plasmid. This plasmid has never been found in other tet(X4)-harboring strains and could be cotransferred with a conjugative plasmid to the recipient strain. Our findings indicate that the tet(X4) gene breaks through its original bacterial species and spreads to some important nosocomial pathogens, which posed a serious threat to public health.

          Related collections

          Most cited references18

          • Record: found
          • Abstract: found
          • Article: not found

          Mobility of plasmids.

          Plasmids are key vectors of horizontal gene transfer and essential genetic engineering tools. They code for genes involved in many aspects of microbial biology, including detoxication, virulence, ecological interactions, and antibiotic resistance. While many studies have decorticated the mechanisms of mobility in model plasmids, the identification and characterization of plasmid mobility from genome data are unexplored. By reviewing the available data and literature, we established a computational protocol to identify and classify conjugation and mobilization genetic modules in 1,730 plasmids. This allowed the accurate classification of proteobacterial conjugative or mobilizable systems in a combination of four mating pair formation and six relaxase families. The available evidence suggests that half of the plasmids are nonmobilizable and that half of the remaining plasmids are conjugative. Some conjugative systems are much more abundant than others and preferably associated with some clades or plasmid sizes. Most very large plasmids are nonmobilizable, with evidence of ongoing domestication into secondary chromosomes. The evolution of conjugation elements shows ancient divergence between mobility systems, with relaxases and type IV coupling proteins (T4CPs) often following separate paths from type IV secretion systems. Phylogenetic patterns of mobility proteins are consistent with the phylogeny of the host prokaryotes, suggesting that plasmid mobility is in general circumscribed within large clades. Our survey suggests the existence of unsuspected new relaxases in archaea and new conjugation systems in cyanobacteria and actinobacteria. Few genes, e.g., T4CPs, relaxases, and VirB4, are at the core of plasmid conjugation, and together with accessory genes, they have evolved into specific systems adapted to specific physiological and ecological contexts.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Emergence of plasmid-mediated high-level tigecycline resistance genes in animals and humans

            Tigecycline is a last-resort antibiotic that is used to treat severe infections caused by extensively drug-resistant bacteria. tet(X) has been shown to encode a flavin-dependent monooxygenase that modifies tigecycline1,2. Here, we report two unique mobile tigecycline-resistance genes, tet(X3) and tet(X4), in numerous Enterobacteriaceae and Acinetobacter that were isolated from animals, meat for consumption and humans. Tet(X3) and Tet(X4) inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline. Both tet(X3) and tet(X4) increase (by 64-128-fold) the tigecycline minimal inhibitory concentration values for Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii. In addition, both Tet(X3) (A. baumannii) and Tet(X4) (E. coli) significantly compromise tigecycline in in vivo infection models. Both tet(X3) and tet(X4) are adjacent to insertion sequence ISVsa3 on their respective conjugative plasmids and confer a mild fitness cost (relative fitness of >0.704). Database mining and retrospective screening analyses confirm that tet(X3) and tet(X4) are globally present in clinical bacteria-even in the same bacteria as blaNDM-1, resulting in resistance to both tigecycline and carbapenems. Our findings suggest that both the surveillance of tet(X) variants in clinical and animal sectors and the use of tetracyclines in food production require urgent global attention.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Replicon sequence typing of IncF plasmids carrying virulence and resistance determinants.

              IncF plasmids are frequently encountered in clinical enterobacterial strains associated with the dissemination of relevant antimicrobial resistance and virulence genes. These plasmids are usually heterogeneous in size and carry multiple replicons, and technical difficulties can impair the comparison and detection of related plasmids by restriction fragment length polymorphism analysis. We devised a rapid sequence-based typing scheme to categorize the members of this plasmid family into homogeneous groups. We compared the available IncF replicon sequences, identifying the combination of the different IncF replicon alleles as the discriminating characteristic of these plasmid scaffolds. An IncF typing method based on PCR amplification and sequence typing of the IncF replicons was devised. A collection of IncF plasmids carrying resistance and/or virulence genes, identified in strains from different sources and geographical origins, was tested with this typing system. We devised a replicon sequence typing (RST) scheme discriminating IncF plasmid variants. This system was tested on the collection of IncF plasmids, demonstrating that it was useful for the discrimination of plasmids carrying the same resistance gene (i.e. the bla(CTX-M-15) gene), but also recognized strictly related virulence plasmids (i.e. IncFIme plasmids). The PCR-based replicon typing (PBRT) system was also updated by including new primer pairs to allow the identification of the Salmonella, Klebsiella and Yersinia IncF plasmids. The ability to recognize and sub-categorize IncF plasmids by RST in homogeneous groups on the basis of their phylogenetic relatedness can be helpful in analysing their distribution in nature and discovering their evolutionary origin.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                Microbiol Spectr
                Microbiol Spectr
                spectrum
                Microbiology Spectrum
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2165-0497
                9 February 2022
                Jan-Feb 2022
                9 February 2022
                : 10
                : 1
                : e01081-21
                Affiliations
                [a ] Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural Universitygrid.22935.3f, , Beijing, People’s Republic of China
                [b ] Department of Laboratory Medicine, First Medical Centre, Chinese PLA General Hospitalgrid.414252.4, , Beijing, People’s Republic of China
                [c ] National Health Commission Key Laboratory of Food Safety Risk Assessment, Food Safety Research Unit (2019RU014) of the Chinese Academy of Medical Science, China National Center for Food Safety Risk Assessment, Beijing, People’s Republic of China
                Peking University People's Hospital
                Author notes

                The authors declare no conflict of interest.

                Author information
                https://orcid.org/0000-0002-8112-8270
                https://orcid.org/0000-0002-5928-9377
                Article
                01081-21 spectrum.01081-21
                10.1128/spectrum.01081-21
                8826827
                35138117
                d05cddde-c740-42ee-83b8-bae0f7d1ea0d
                Copyright © 2022 Zhai et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 29 July 2021
                : 17 January 2022
                Page count
                supplementary-material: 1, Figures: 1, Tables: 0, Equations: 0, References: 19, Pages: 5, Words: 2965
                Funding
                Funded by: National Natural Science Foundation of China (NSFC), FundRef https://doi.org/10.13039/501100001809;
                Award ID: 31930110
                Award Recipient : Award Recipient : Award Recipient :
                Funded by: MOST | National Key Research and Development Program of China (NKRDPC), FundRef https://doi.org/10.13039/501100012166;
                Award ID: 2017YFC1601502
                Award Recipient :
                Funded by: National Natural Science Foundation of China (NSFC), FundRef https://doi.org/10.13039/501100001809;
                Award ID: 81991535
                Award Recipient :
                Funded by: National Natural Science Foundation of China (NSFC), FundRef https://doi.org/10.13039/501100001809;
                Award ID: 32002340
                Award Recipient :
                Categories
                Observation
                clinical-microbiology, Clinical Microbiology
                Custom metadata
                January/February 2022

                tet(x4),klebsiella pneumoniae,tigecycline resistance,incfii

                Comments

                Comment on this article