Abstract
In this study, a detailed genetic dissection of the huge and complex bla NDM-carrying genetic elements and their related mobile genetic elements was performed in Enterobacteriaceae. An extensive comparison was applied to 12 chromosomal genetic elements, including six sequenced in this study and the other six from GenBank. These 12 genetic elements were divided into five groups: a novel IME Tn6588; two related IMEs Tn6523 (SGI1) and Tn6589; four related ICEs Tn6512 (R391), Tn6575 (ICEPvuChnBC22), Tn6576, and Tn6577; Tn7 and its derivatives Tn6726 and 40.7-kb Tn7-related element; and two related IMEs Tn6591 (GIsul2) and Tn6590. At least 51 resistance genes, involved in resistance to 18 different categories of antibiotics and heavy metals, were found in these 12 genetic elements. Notably, Tn6576 carried another ICE Tn6582. In particular, the six bla NDM-carrying genetic elements Tn6588, Tn6589, Tn6575, Tn6576, Tn6726, and 40.7-kb Tn7-related element contained large accessory multidrug resistance (MDR) regions, each of which had a very complex mosaic structure that comprised intact or residual mobile genetic elements including insertion sequences, unit or composite transposons, integrons, and putative resistance units. Core bla NDM genetic environments manifested as four different Tn125 derivatives and, notably, two or more copies of relevant Tn125 derivatives were found in each of Tn6576, Tn6588, Tn6589, and 40.7-kb Tn7-related element. The huge and complex bla NDM-carrying genetic elements were assembled from complex transposition and homolog recombination. Firstly identified were eight novel mobile elements, including three ICEs Tn6576, Tn6577, and Tn6582, two IMEs, Tn6588 and Tn6589, two composite transposons Tn6580a and Tn6580b, and one integron In1718.
Highlights
New Delhi metallo-b-lactamase (NDM) is able to hydrolyze most b-lactams except aztreonam and mediates resistance to penicillins, cephalosporins, and carbapenems (Yong et al, 2009)
The complete genome sequences of four blaNDM-carrying isolates Providencia rettgeri 1701091, Proteus mirabilis 1701092, K. pneumoniae QD23, and Providencia rettgeri 51003 were determined in this work through high-throughput genome sequencing
A total of six chromosome-borne accessory resistance regions were identified: blaNDM-1/-3-carrying Tn6588, Tn6589, Tn6576, and 40.7-kb Tn7-related element from strains 1701091, 1701092, QD23, and 51003, respectively; tetA(C)- and blaCTX-M-14-carrying Tn6577 were from strain 1701092; and strAB-carrying Tn6590 was from strain 51003
Summary
New Delhi metallo-b-lactamase (NDM) is able to hydrolyze most b-lactams except aztreonam and mediates resistance to penicillins, cephalosporins, and carbapenems (Yong et al, 2009). With the transposition of Tn125, blaNDM is disseminated among Acinetobacter, Enterobacteriaceae and Pseudomonas species; Tn125 and its blaNDM-carrying derivatives, with various truncations and deletions, can be found in the accessory resistance regions of bacterial plasmids or chromosomes (Wu et al, 2019). ICEs have the ability to transfer between cells because of their self-encoded conjugation function. It is typically composed of attL (attachment site at the left end), int (integrase), xis (excisionase), rlx (relaxase), oriT (origin of conjugative replication), cpl (coupling protein), a P (TivB)- or F (TivF)type T4SS machinery (mating pair formation), and attR (attachment site at the right end). Tn7 is a unit transposon with the ability to integrate into bacterial chromosomes and plasmids, and it encodes five core transposition determinants TnsA and TnsB (transposases), TnsC (regulator), and TnsD and TnsE (DNA-binding proteins), as well as three TnsB-binding sites and four TnsB-binding sites at its left and right ends, respectively (Peters, 2014)
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