Affiliation:
1. Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
Abstract
ABSTRACT
Multidrug-resistant
Enterobacteriaceae
, a prominent family of gram-negative pathogenic bacteria, causes a wide range of severe diseases. Strains carrying the mobile colistin resistance (
mcr-1
) gene show resistance to polymyxin, the last line of defense against multidrug-resistant gram-negative bacteria. However, the transmission of
mcr-1
is not well understood. In this study, genomes of
mcr-1
-positive strains were obtained from the NCBI database, revealing their widespread distribution in China. We also showed that IS
Apl1
, a crucial factor in
mcr-1
transmission, is capable of self-transposition. Moreover, the self-cyclization of IS
Apl1
is mediated by its own encoded transposase. The electrophoretic mobility shift assay experiment validated that the transposase can bind to the inverted repeats (IRs) on both ends, facilitating the cyclization of IS
Apl1
. Through knockout or shortening of IRs at both ends of IS
Apl1
, we demonstrated that the cyclization of IS
Apl1
is dependent on the sequences of the IRs at both ends. Simultaneously, altering the ATCG content of the bases at both ends of IS
Apl1
can impact the excision rate by modifying the binding ability between IRs and ISAPL1. Finally, we showed that heat-unstable nucleoid protein (HU) can inhibit IS
Apl1
transposition by binding to the IRs and preventing ISAPL1 binding and expression. In conclusion, the regulation of IS
Apl1
-self-circling is predominantly controlled by the inverted repeat (IR) sequence and the HU protein. This molecular mechanism deepens our comprehension of
mcr-1
dissemination.
Funder
MOE | Fundamental Research Funds for the Central Universities
MOST | National Key Research and Development Program of China
MOST | National Natural Science Foundation of China
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology