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Antibiotics
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Bacterial Drug Resistance and Transmission Mechanism
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Bacterial Drug Resistance and Transmission Mechanism

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Genetic and Biochemical Studies of Antibiotic Activity and Resistance".

Deadline for manuscript submissions: closed (10 March 2022) | Viewed by 18677

Special Issue Editor

Prof. Dr. Yongfei Hu

E-Mail Website1 Website2
Guest Editor
State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
Interests: antibiotic resistance; gut microbiome; metagenomics; bacterial genomics; probiotics

Special Issue Information

Dear Colleagues,

The use of antimicrobial drugs in both human and animal medicine leads to the rapid development and dissemination of antimicrobial resistance (AMR) in bacteria. In recent years, the emergence of new AMR genes as well as multidrug resistant bacteria is threatening the achievements of modern medical in the fight against bacterial infection. Bacteria have evolved different mechanisms, intrinsic or acquired, to become resistant to antimicrobial drugs, involving membrane barriers, target mutations, efflux pumps, and drug-inactivating enzymes. All these mechanisms are regarded natural in bacteria, but the selection pressure of antimicrobial drugs enriches the resistant community or accelerates the spread of AMR genes from resistant to sensitive individuals. The dissemination of AMR among bacteria is mainly dependent on horizontal gene transfer (HGT), and a variety of mobile genetic elements (MGEs) are involved in this process. The AMR dilemma not only exists in humans, but also in farm and wild animals and in environments. To tackle this crisis, a one-health strategy should be implemented, and researchers from different fields should participate and collaborate toward better understanding AMR. Therefore, this Special Issue welcomes submissions from different research fields using cutting-edge methods to study the drug resistance mechanisms, evolution and transfer of AMR genes, and the spread and transmission pathways and mechanisms of AMR.

Prof. Yongfei Hu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antimicrobial resistance
  • drug resistance mechanism
  • mobile genetic elements
  • horizontal gene transfer
  • genomics
  • metagenomics

Published Papers (7 papers)

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Research

13 pages, 4337 KiB  
Article
High Carriage of Extended-Spectrum, Beta Lactamase-Producing, and Colistin-Resistant Enterobacteriaceae in Tibetan Outpatients with Diarrhea
by Zhe Li, Jiaqi Li, Jiaqi Liu, Yao Peng, Zhenpeng Li, Mengyu Wang, Ge Zhang, Geruo Qu, Jingyun Zhang, Xiuping Fu, Xia Chen, Ciren Dunzhu, Shan Lu, Xin Lu, Jialiang Xu and Biao Kan
Antibiotics 2022, 11(4), 508; https://doi.org/10.3390/antibiotics11040508 - 11 Apr 2022
Cited by 1 | Viewed by 1732
Abstract
Antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) have been detected in human-impacted habitats, especially in densely populated cities. The Qinghai–Tibet Plateau is located far from the heavily populated regions of China, and Tibetan residents have distinct dietary habits and gut microbes. Antibiotic-resistance monitoring [...] Read more.
Antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) have been detected in human-impacted habitats, especially in densely populated cities. The Qinghai–Tibet Plateau is located far from the heavily populated regions of China, and Tibetan residents have distinct dietary habits and gut microbes. Antibiotic-resistance monitoring in the Tibetan population is rare. Here, we collected stool samples from Tibetan outpatients with diarrhea. From 59 samples, 48 antibiotic-resistant Enterobacteriaceae isolates were obtained, including 19 extended-spectrum beta lactamase (ESBL)-producing isolates from 16 patients and 29 polymyxin-resistant isolates from 22 patients. Either ESBL or mcr genes were found in 17 Escherichia coli isolates, approximately 58.8% of which were multidrug-resistant, and ten incompatible plasmid types were found. The gene blaCTX-M was a common genotype in the ESBL-producing E. coli isolates. Four E. coli isolates contained mcr-1. The same mcr-1-carrying plasmid was found in distinct E. coli isolates obtained from the same sample, thus confirming horizontal transmission of mcr-1 between bacteria. Genomic clustering of E. coli isolates obtained from Lhasa, with strains from other regions providing evidence of clone spreading. Our results reveal a strong presence of ARB and ARGs in Tibetan outpatients with diarrhea, implying that ARB and ARGs should be monitored in the Tibetan population. Full article
(This article belongs to the Special Issue Bacterial Drug Resistance and Transmission Mechanism)
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13 pages, 1743 KiB  
Article
DNA Methyltransferase HsdM Induce Drug Resistance on Mycobacterium tuberculosis via Multiple Effects
by Hongqian Chu, Yongfei Hu, Bing Zhang, Zhaogang Sun and Baoli Zhu
Antibiotics 2021, 10(12), 1544; https://doi.org/10.3390/antibiotics10121544 - 16 Dec 2021
Cited by 6 | Viewed by 2364
Abstract
Besides the genomic variants, epigenetic mechanisms such as DNA methylation also have an effect on drug resistance. This study aimed to investigate the methylomes of totally/extensively drug-resistant M. tuberculosis clinical isolates using the PacBio single-molecule real-time technology. The results showed they were almost [...] Read more.
Besides the genomic variants, epigenetic mechanisms such as DNA methylation also have an effect on drug resistance. This study aimed to investigate the methylomes of totally/extensively drug-resistant M. tuberculosis clinical isolates using the PacBio single-molecule real-time technology. The results showed they were almost the same as the pan-susceptible ones. Genetics and bioinformatics analysis confirmed three DNA methyltransferases—MamA, MamB, and HsdM. Moreover, anti-tuberculosis drug treatment did not change the methylomes. In addition, the knockout of the DNA methyltransferase hsdM gene in the extensively drug-resistant clinical isolate 11826 revealed that the motifs of GTAYN4ATC modified by HsdM were completely demethylated. Furthermore, the results of the methylated DNA target analysis found that HsdM was mainly involved in redox-related pathways, especially the prodrug isoniazid active protein KatG. HsdM also targeted three drug-targeted genes, eis, embB, and gyrA, and three drug transporters (Rv0194, Rv1410, and Rv1877), which mildly affected the drug susceptibility. The overexpression of HsdM in M. smegmatis increased the basal mutation rate. Our results suggested that DNA methyltransferase HsdM affected the drug resistance of M. tuberculosis by modulating the gene expression of redox, drug targets and transporters, and gene mutation. Full article
(This article belongs to the Special Issue Bacterial Drug Resistance and Transmission Mechanism)
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11 pages, 1492 KiB  
Article
Streptococcus sputorum, a Novel Member of Streptococcus with Multidrug Resistance, Exhibits Cytotoxicity
by Chao Wang, Yuan Zeng, Mengyu Wei, Lanqing Cui, Yuqin Song, Gang Zhang, Yun Li and Jie Feng
Antibiotics 2021, 10(12), 1532; https://doi.org/10.3390/antibiotics10121532 - 14 Dec 2021
Viewed by 1964
Abstract
We describe the genomic and phenotypic characteristics of a novel member of Streptococcus with multidrug resistance (MDR) isolated from hospital samples. Strains SP218 and SP219 were identified as a novel Streptococcus, S. sputorum, using whole-genome sequencing and biochemical tests. Average [...] Read more.
We describe the genomic and phenotypic characteristics of a novel member of Streptococcus with multidrug resistance (MDR) isolated from hospital samples. Strains SP218 and SP219 were identified as a novel Streptococcus, S. sputorum, using whole-genome sequencing and biochemical tests. Average nucleotide identity values of strains SP218 and SP219 with S. pseudopneumoniae IS7493 and S. pneumoniae ST556 were 94.3% and 93.3%, respectively. Genome-to-genome distance values of strains SP218 and SP219 with S. pseudopneumoniae IS7493 and S. pneumoniae ST556 were 56.70% (54–59.5%) and 56.40% (52.8–59.9%), respectively. The biochemical test results distinguished these strains from S. pseudopneumoniae and S. pneumoniae, particularly hydrolysis of equine urate and utilization of ribose to produce acid. These isolates were resistant to six major classes of antibiotics, which correlated with horizontal gene transfer and mutation. Notably, strain SP219 exhibited cytotoxicity against human lung epithelial cell line A549. Our results indicate the pathogenic potential of S. sputorum, and provide valuable insights into mitis group of streptococci. Full article
(This article belongs to the Special Issue Bacterial Drug Resistance and Transmission Mechanism)
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15 pages, 3622 KiB  
Article
Genomic Characterization of a Proteus sp. Strain of Animal Origin Co-Carrying blaNDM-1 and lnu(G)
by Ying Li, Yichuan Qiu, Junping She, Xu Wang, Xiaoyi Dai and Luhua Zhang
Antibiotics 2021, 10(11), 1411; https://doi.org/10.3390/antibiotics10111411 - 18 Nov 2021
Cited by 5 | Viewed by 1864
Abstract
The emergence of carbapenem-resistant Proteus represents a serious threat to global public health due to limited antibiotic treatment options. Here, we characterize a Proteus isolate NMG38-2 of swine origin that exhibits extensive drug resistance, including carbapenems. Whole-genome sequencing based on Illumina and MinION [...] Read more.
The emergence of carbapenem-resistant Proteus represents a serious threat to global public health due to limited antibiotic treatment options. Here, we characterize a Proteus isolate NMG38-2 of swine origin that exhibits extensive drug resistance, including carbapenems. Whole-genome sequencing based on Illumina and MinION platforms showed that NMG38-2 contains 24 acquired antibiotic resistance genes and three plasmids, among which, pNDM_NMG38-2, a pPvSC3-like plasmid, is transferable and co-carries blaNDM-1 and lnu(G). Sequence analysis of pPvSC3-like plasmids showed that they share a conserved backbone but have a diverse accessory module with complex chimera structures bearing abundant resistance genes, which are facilitated by transposons and/or homologous recombination. The acquisition of blaNDM-1 in pNDM_NMG38-2 was due to the ISCR1-mediated integration event. Comprehensive analysis of the lnu(G)-bearing cassettes carried by bacterial plasmids or chromosomes revealed a diversification of its genetic contexts, with Tn6260 and ISPst2 elements being the leading contributors to the dissemination of lnu(G) in Enterococcus and Enterobacteriaceae, respectively. In conclusion, this study provides a better understanding of the genetic features of pPvSC3-like plasmids, which represent a novel plasmid group as a vehicle mediating the dissemination of blaNDM-1 among bacteria species. Moreover, our results highlight the central roles of Tn6260 and ISPst2 in the spread of lnu(G). Full article
(This article belongs to the Special Issue Bacterial Drug Resistance and Transmission Mechanism)
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11 pages, 1593 KiB  
Article
Analysis on Drug-Resistance-Associated Mutations among Multidrug-Resistant Mycobacterium tuberculosis Isolates in China
by Hongbing Jia, Yuhui Xu and Zhaogang Sun
Antibiotics 2021, 10(11), 1367; https://doi.org/10.3390/antibiotics10111367 - 08 Nov 2021
Cited by 3 | Viewed by 4615
Abstract
As the causative bacteria of tuberculosis, Mycobacteriumtuberculosis (M. tb) is aggravated by the emergence of its multidrug-resistant isolates in China. Mutations of six of the most frequently reported resistant genes (rpoB, katG, inhA, embB, gyrA, and rpsL) were detected [...] Read more.
As the causative bacteria of tuberculosis, Mycobacteriumtuberculosis (M. tb) is aggravated by the emergence of its multidrug-resistant isolates in China. Mutations of six of the most frequently reported resistant genes (rpoB, katG, inhA, embB, gyrA, and rpsL) were detected for rifampicin (RIF), isoniazid (INH), ethambutol (EMB), ofloxacin (OFX), and streptomycin (STR) in this study. The amino acid missense mutations (MMs) and their corresponding single nucleotide polymorphism mutations for all drug-resistant (DR) isolates are described in detail. All isolates were divided into non-extensively drug-resistant (Non-XDR) and preXDR/XDR groups. No statistical differences were detected among MMs and linked MMs (LMs) between the two groups, except for rpsL 88 (p = 0.037). In the preXDR/XDR group, the occurrence of MMs in rpoB, katG, and inhA developed phenotypic resistance and MMs of rpoB 531, katG 315, rpsL 43, and rpsL 88 could develop high levels of DR. It is necessary to carry out epidemiological investigations of DR gene mutations in the local region, and thus provide necessary data to support the design of new technologies for rapid detection of resistant M. tb and the optimization of detection targets. Full article
(This article belongs to the Special Issue Bacterial Drug Resistance and Transmission Mechanism)
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12 pages, 1429 KiB  
Article
The Mycobacterial DNA Methyltransferase HsdM Decreases Intrinsic Isoniazid Susceptibility
by Xinling Hu, Xintong Zhou, Tong Yin, Keyu Chen, Yongfei Hu, Baoli Zhu and Kaixia Mi
Antibiotics 2021, 10(11), 1323; https://doi.org/10.3390/antibiotics10111323 - 29 Oct 2021
Cited by 5 | Viewed by 3138
Abstract
Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is a serious infectious disease worldwide. Multidrug-resistant TB (MDR-TB) remains a global problem, and the understanding of this resistance is incomplete. Studies suggested that DNA methylation promotes bacterial adaptability to antibiotic treatment, but the role [...] Read more.
Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is a serious infectious disease worldwide. Multidrug-resistant TB (MDR-TB) remains a global problem, and the understanding of this resistance is incomplete. Studies suggested that DNA methylation promotes bacterial adaptability to antibiotic treatment, but the role of mycobacterial HsdM in drug susceptibility has not been explored. Here, we constructed an inactivated Mycobacterium bovis (BCG) strain, ΔhsdM. ΔhsdM shows growth advantages over wild-type BCG under isoniazid treatment and hypoxia-induced stress. Using high-precision PacBio single-molecule real-time sequencing to compare the ΔhsdM and BCG methylomes, we identified 219 methylated HsdM substrates. Bioinformatics analysis showed that most HsdM-modified genes were enriched in respiration- and energy-related pathways. qPCR showed that HsdM-modified genes directly affected their own transcription, indicating an altered redox regulation. The use of the latent Wayne model revealed that ΔhsdM had growth advantages over wild-type BCG and that HsdM regulated trcR mRNA levels, which may be crucial in regulating transition from latency to reactivation. We found that HsdM regulated corresponding transcription levels via gene methylation; thus, altering the mycobacterial redox status and decreasing the bacterial susceptibility to isoniazid, which is closely correlated with the redox status. Our results provide valuable insight into DNA methylation on drug susceptibility. Full article
(This article belongs to the Special Issue Bacterial Drug Resistance and Transmission Mechanism)
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18 pages, 2072 KiB  
Article
Co-Occurrence of blaOXA-23 in the Chromosome and Plasmid: Increased Fitness in Carbapenem-Resistant Acinetobacter baumannii
by Zhiren Wang, Henan Li, Jiangang Zhang and Hui Wang
Antibiotics 2021, 10(10), 1196; https://doi.org/10.3390/antibiotics10101196 - 01 Oct 2021
Cited by 10 | Viewed by 1941
Abstract
This study aims to explore the co-occurrence of chromosomal and plasmid blaOXA-23 in carbapenem-resistant A. baumannii (CRAB) and its influence on phenotypes. A total of 11 CRAB isolates containing copies of blaOXA-23 on the chromosome and plasmid (CO), as well as [...] Read more.
This study aims to explore the co-occurrence of chromosomal and plasmid blaOXA-23 in carbapenem-resistant A. baumannii (CRAB) and its influence on phenotypes. A total of 11 CRAB isolates containing copies of blaOXA-23 on the chromosome and plasmid (CO), as well as 18 closely related isolates with blaOXA-23, located on either the chromosome or plasmid (SI), were selected for the determination of antibiotic susceptibility, virulence phenotype, and characteristic genomic differences. The co-occurrence of blaOXA-23 on the CRAB chromosome and plasmids did not enhance carbapenem resistance, but trimethoprim/sulfamethoxazole exhibited significantly reduced minimum inhibitory concentrations in CO. CO demonstrated a higher degree of fitness compared to SI. An increased biofilm formation ability and serum tolerance were also identified in CO, which may be associated with virulence genes, which include csuD, entE, pgaA, and plc. blaOXA-23-carrying transposons were found at different insertion sites on the chromosome. The most common site was AbaR-type genomic islands (50%). Two types of plasmids were found in CO. The co-occurrence of blaOXA-23 on the chromosome and a plasmid in CRAB had little effect on carbapenem susceptibility but was accompanied by increased fitness and virulence. Different origins and independent insertions of blaOXA-23-carrying transposons were identified in both the chromosomal and plasmid sequences. Full article
(This article belongs to the Special Issue Bacterial Drug Resistance and Transmission Mechanism)
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