Mobile tigecycline resistance (MTR) threatens the clinical efficacy of the salvage antibiotic, tigecycline (TIG) used in treating deadly infections in humans caused by superbugs (multidrug-, extensively drug-, and pandrug-resistant bacteria), including carbapenem- and colistin-resistant bacteria. Currently, non-mobile tet(X) and mobile plasmid-mediated transmissible tet(X) and resistance-nodulation-division (RND) efflux pump tmexCD-toprJ genes, conferring high-level TIG (HLT) resistance have been detected in humans, animals, and environmental ecosystems. Given the increasing rate of development and spread of plasmid-mediated resistance against the two last-resort antibiotics, colistin (COL) and TIG, there is a need to alert the global community on the emergence and spread of plasmid-mediated HLT resistance and the need for nations, especially developing countries, to increase their antimicrobial stewardship. Justifiably, MTR spread projects One Health ramifications and portends a monumental threat to global public and animal health, which could lead to outrageous health and economic impact due to limited options for therapy. To delve more into this very important subject matter, this current work will discuss why MTR is an emerging health catastrophe requiring urgent One Health global intervention, which has been constructed as follows: (a) antimicrobial activity of TIG; (b) mechanism of TIG resistance; (c) distribution, reservoirs, and traits of MTR gene-harboring isolates; (d) causes of MTR development; (e) possible MTR gene transfer mode and One Health implication; and (f) MTR spread and mitigating strategies.

https://www.frontiersin.org/articles/10.3389/fmicb.2022.808744/pdf

Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention

The emergence of pathogens is conferring resistance to last-resort therapies such as tigecycline, colistin, and carbapenems, limiting the therapeutic options, and raising concerns about the emergence of new “superbugs.” This study reports the first incident of a blaNDM–5 and tet(X4) co-harboring Escherichia coli with resistance to carbapenem and tigecycline recovered as the causative agent of a urinary tract infection in a 94-year-old patient. The E. coli strain ECCL209 carries multiple resistance genes [i.e., blaTEM–1B, blaNDM–5, blaCMY–2, aadA22, florR, erm(B), mph(A), erm(42), lnuG, qnrS1, and sul2] and exhibits resistance to almost all clinically used antibiotics. MLST analysis found that the strain belongs to ST648, considered a worldwide high-risk pandemic clone. Moreover, multiple plasmid incompatibility types were detected, i.e., IncHI1A, IncHI1B, IncFII, IncFIA, IncFIB, IncQ1, Col, and IncX4. Genetic analysis revealed that blaNDM–5 and tet(X4) genes were localized on two hybrid plasmids with multiple replicons. Continuous monitoring studies are suggested to quantify the antimicrobial resistance and assess the dissemination of such superbugs into a human healthcare setting.

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Coexistence of blaNDM–5 and tet(X4) in international high-risk Escherichia coli clone ST648 of human origin in China

IncX3 plasmids are narrow host range plasmids mostly found in Enterobacteriaceae with great conjugation ability, high stability, no fitness cost, and the ability to improve biofilm formation in their bacterial hosts. IncX3 plasmids have spread swiftly, primarily in several nations and among different species over the last 10 years. blaNDM, blaKPC, and blaOXA-181 are the carbapenemase genes carried by IncX3 plasmids. Among them, blaNDM is often located on the IncX3 plasmid, which is deemed as the primary vehicle of blaNDM transmission. Isolates harboring IncX3 plasmids are found in nations all over the world from human, animal, and environmental sources. Cointegrate plasmids related to IncX3 have recently been discovered to increase the antibiotic resistance spectrum and potentially broaden the host range of plasmids, restricting the use of antibiotics in the clinic. There are, however, few reviews based on the physiological and epidemiological properties of IncX3 plasmid, as well as studies on the plasmid itself. Hence, we conducted a retrospective literature review to summarize the characteristics of IncX3 plasmids aiming to provide a theoretical basis for controlling the global prevalence of IncX3 plasmids and directions for further research on the functions of the related genes on the IncX3 plasmid.

Global prevalence, characteristics, and future prospects of IncX3 plasmids: A review

The emergence of plasmid-mediated colistin resistance gene mcr-1 incurs great concerns. Since the close proximity of pigeons with humans, it is significant to understand the prevalence and molecular characterization of mcr-1-positive isolates in pigeons, to provide a rationale for controlling its spread. ABSTRACT The prevalence of colistin-resistant bacteria limited the usage of colistin in the treatment of clinical multidrug-resistant Gram-negative bacterial infections. Here, we aimed to investigate the prevalence and molecular characterization of mcr-1-carrying isolates from pigeons close to humans following the ban on the use of colistin as an animal feed additive in China. Methods, including PCR, antimicrobial susceptibility testing, conjugation experiments, plasmid replicon typing, genome sequencing, bioinformatics analysis, measurement of growth curves, competition experiments, and plasmid stability assays were used to identify and characterize mcr-1-positive isolates. In total, 45 mcr-1-positive E. coli isolates were acquired from 100 fecal samples, and MICs of colistin ranged from 4 to 8 mg/L. The prevalence of mcr-1-positive E. coli isolates from pigeons was mainly mediated by IncX4 plasmids (39/45), including transferable mcr-1-bearing IncX4 plasmids with fitness advantage in 21 isolates, and nontransferable mcr-1-bearing IncX4 plasmids with fitness disadvantage in 18 isolates. There is a similar structure among the 6 mcr-1-bearing nontransferable IncX4 plasmids and 10 mcr-1-bearing transferable IncX4 plasmids in 16 E. coli isolates that have been sequenced. Plasmid transferability evaluation indicated that the same IncX4 plasmid has different transferability in different E. coli isolates. In conclusion, this study demonstrates that pigeons could act as potential reservoirs for the spread of mcr-1-positive E. coli in China. Transferability of IncX4 plasmids may be influenced by host chromosome in the same bacterial species. Additional research on the factors influencing the transferability of IncX4 plasmids in different bacterial hosts is required to help combat antimicrobial resistance. IMPORTANCE The emergence of plasmid-mediated colistin resistance gene mcr-1 incurs great concerns. Since the close proximity of pigeons with humans, it is significant to understand the prevalence and molecular characterization of mcr-1-positive isolates in pigeons, to provide a rationale for controlling its spread. Here, we found that the prevalence of mcr-1-positive E. coli from pigeons was mainly mediated by IncX4 plasmids. However, different transferability and fitness of mcr-1-bearing IncX4 plasmids in E. coli were observed, which demonstrated that transferability of IncX4 plasmids could be affected not only by genes on plasmids, but also by chromosomal factors in the same bacterial species. Our finding provided a new insight on studying the factors influencing the transferability of plasmids.

https://doi.org/10.1128/spectrum.03639-22

The Prevalence of Plasmid-Mediated Colistin Resistance Gene mcr-1 and Different Transferability and Fitness of mcr-1-Bearing IncX4 Plasmids in Escherichia coli from Pigeons

In the material transfer area, the belt is exposed to considerable damage, the energy of falling material is lost, and there is significant dust and noise. One of the most common causes of failure is transfer chute blockage, when the flow of material in the free fall or loading zone is disturbed by oversized rock parts or other objects, e.g., rock bolts. The failure of a single transfer point may cause the entire transport route to be excluded from work and associated with costly breakdowns. For this reason, those places require continuous monitoring and special surveillance measures. The number of methods for monitoring this type of blockage is limited. The article presents the research results on the possibility of visual monitoring of the transfer operating status on an object in an underground copper ore mine. A standard industrial RGB camera was used to obtain the video material from the transfer point area, and the recorded frames were processed by a detection algorithm based on a neural network. The CNN autoencoder was taught to reconstruct the image of regular transfer operating conditions. A data set with the recorded transfer blockage state was used for validation.

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Detection of Blockages of the Belt Conveyor Transfer Point Using an RGB Camera and CNN Autoencoder

Tigecycline and colistin are regarded as vital antimicrobials to treat multidrug-resistant (MDR) bacterial infections, such as that caused by carbapenemase-producing Enterobacteriaceae (CPE). Cooccurrence of mobile resistance genes conferring resistance to last-resort antimicrobials in E. coli remains unknown. ABSTRACT Emergence of pathogens harboring multiple resistance genes incurs great concerns. Cooccurrence of mobile resistance genes conferring resistance to tigecycline, colistin, and carbapenems in Escherichia coli has not been investigated. This study aimed to characterize three E. coli isolates coharboring tet(X4), mcr-1, and blaNDM-5. Isolates coharboring tet(X4), mcr-1, and blaNDM-5 were identified and characterized by PCR, Sanger sequencing, antimicrobial susceptibility testing, conjugation assays, Illumina sequencing, nanopore sequencing, and bioinformatic analysis. Three E. coli isolates carrying tet(X4), mcr-1, and blaNDM-5 were identified from pigeons in China. They were resistant to almost all antimicrobials except enrofloxacin. tet(X4) and blaNDM-5 could be conjugated into E. coli C600, but mcr-1 was nontransferable in three isolates. Three isolates belonged to sequence type 6775 (ST6775), and clonal dissemination of isolates carrying tet(X4), mcr-1, and blaNDM-5 existed in the pigeon farm. Genetic analysis revealed that mcr-1 mediated by the Tn6330 was located on the chromosome, tet(X4) was located on the IncFII plasmid, and blaNDM-5 was located on the IncX3 plasmid. We first characterized the E. coli isolates carrying tet(X4), mcr-1, and blaNDM-5 simultaneously. Relevant measures should be taken to decrease the prevalence of pathogens carrying tet(X4), mcr-1, and blaNDM-5. IMPORTANCE Tigecycline and colistin are regarded as vital antimicrobials to treat multidrug-resistant (MDR) bacterial infections, such as that caused by carbapenemase-producing Enterobacteriaceae (CPE). Cooccurrence of mobile resistance genes conferring resistance to last-resort antimicrobials in E. coli remains unknown. Here, we characterized E. coli strains coharboring tet(X4), mcr-1, and blaNDM-5 phenotypically and genetically. Resistance genes tet(X4), mcr-1, and blaNDM-5 were located on transposons or plasmids that were mobile genetic elements related to the capture, accumulation, and dissemination of such important resistance genes. The emergence of E. coli isolates carrying tet(X4), mcr-1, and blaNDM-5 highlights the importance of monitoring the coexistence of novel mobile resistance genes in different settings with a One Health approach. Risk of transmission of such MDR pathogens from animals to humans should be evaluated comprehensively.

Coexistence of tet(X4), mcr-1, and blaNDM-5 in ST6775 Escherichia coli Isolates of Animal Origin in China

With the advancement of smart mines technology, unmanned and Shojinka have received widespread attention, among which unattended crushing station is one of the research directions. To realize unattended crushing station, first of all, it is necessary to detect loose material blockage at the crushing mouth. Based on deep learning (DL) and machine vision (MV) technology, an on-line detection method is studied to trace the blockage in a swift and accurate manner, so that the corresponding detection system can be designed accordingly. The charge coupled device (CCD) industrial camera set above the crushing mouth is used to collect images and input them to the edge computing equipment. The original Single Shot MultiBox Detector (SSD) preprocessing model is trained and optimized before it is combined with the MV technology to detect and then the MV technology is combined to detect whether the crushing mouth is covered. In Ansteel Group GUANBAOSHAN mine, the accuracy of recognition and detection system with human observation was examined for one month, and the tested accuracy is 95%. The experimental results show that the proposed method can detect the crushing mouth blockage in real time, which would solve the problem that the blockage can only be identified by human eyes in traditional method, and provides basic support for the unattended crushing station.

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Detection Method of Crushing Mouth Loose Material Blockage Based on SSD Algorithm

Molecular epidemiology and population genomics of tet(X4), blaNDM or mcr-1 positive Escherichia coli from migratory birds in southeast coast of China.

As a PP, P1 DNA exists as a low-copy-number plasmid and replicates autonomously with a lysogenization style. This unique mode of P1-like elements probably indicates a stable contribution to antibiotic resistance. ABSTRACT The P1-like phage plasmid (PP) has been widely used as a molecular biology tool, but its role as an active accessory cargo element is not fully understood. In this study, we provide insights into the structural features and gene content similarities of 77 P1-like PPs in the RefSeq database. We also describe a P1-like PP carrying a blaCTX-M-55 gene, JL22, which was isolated from a clinical strain of Escherichia coli from a duck farm. P1-like PPs were very similar and conserved based on gene content similarities, with only eight highly variable regions. Importantly, two kinds of replicon types, namely, IncY and p0111, were identified and can be used to specifically identify the P1-like phage. JL22 is similar to P1, acquiring an important foreign DNA fragment with two obvious features, namely, the plasmid replication gene repA′ (p0111) replacing the gene repA (IncY) and a 4,200-bp fragment mobilized by IS1380 and IS5 and containing a blaCTX-M-55 gene and a trpB gene encoding tryptophan synthase (indole salvaging). The JL22 phage could be induced but had no lytic capacities. However, a lysogenic recipient and intact structure of JL22 virions were observed, showing that the extended-spectrum β-lactamase blaCTX-M-55 gene was successfully transferred. Overall, conserved genes can be a good complement to improve the identification efficiency and accuracy in future screening for P1-like PPs. Moreover, the highly conserved structures may be important for their prevalence and dissemination. IMPORTANCE As a PP, P1 DNA exists as a low-copy-number plasmid and replicates autonomously with a lysogenization style. This unique mode of P1-like elements probably indicates a stable contribution to antibiotic resistance. After analyzing these elements, we show that P1-like PPs are very similar and conserved, with only eight highly variable regions. Moreover, we observed the occurrence of replicon IncY and p0111 only in the P1-like PP community, implying that these conserved regions, coupled with IncY and p0111, can be an important complement in future screening of P1-like PPs. Identification and characterization of JL22 confirmed our findings that major changes were located in variable regions, including the first detection of blaCTX-M-55 in such a mobile genetic element. This suggests that these variable regions may facilitate foreign DNA mobilization. This study features a comprehensive genetic analysis of P1-like PPs, providing new insights into the dissemination mechanisms of antibiotic resistance through P1 PPs.

Wenhui Zhang

Papers

Coexistence of tet(X4), mcr-1, and blaNDM-5 in ST6775 Escherichia coli Isolates of Animal Origin in China

Detection Method of Crushing Mouth Loose Material Blockage Based on SSD Algorithm

Molecular epidemiology and population genomics of tet(X4), blaNDM or mcr-1 positive Escherichia coli from migratory birds in southeast coast of China.

The Prevalence of Plasmid-Mediated Colistin Resistance Gene mcr-1 and Different Transferability and Fitness of mcr-1-Bearing IncX4 Plasmids in Escherichia coli from Pigeons

Similarities of P1-Like Phage Plasmids and Their Role in the Dissemination of blaCTX-M-55