scholarly journals The History of Colistin Resistance Mechanisms in Bacteria: Progress and Challenges

2021 ◽  
Vol 9 (2) ◽  
pp. 442
Author(s):  
Mouna Hamel ◽  
Jean-Marc Rolain ◽  
Sophie Alexandra Baron

Since 2015, the discovery of colistin resistance genes has been limited to the characterization of new mobile colistin resistance (mcr) gene variants. However, given the complexity of the mechanisms involved, there are many colistin-resistant bacterial strains whose mechanism remains unknown and whose exploitation requires complementary technologies. In this review, through the history of colistin, we underline the methods used over the last decades, both old and recent, to facilitate the discovery of the main colistin resistance mechanisms and how new technological approaches may help to improve the rapid and efficient exploration of new target genes. To accomplish this, a systematic search was carried out via PubMed and Google Scholar on published data concerning polymyxin resistance from 1950 to 2020 using terms most related to colistin. This review first explores the history of the discovery of the mechanisms of action and resistance to colistin, based on the technologies deployed. Then we focus on the most advanced technologies used, such as MALDI-TOF-MS, high throughput sequencing or the genetic toolbox. Finally, we outline promising new approaches, such as omics tools and CRISPR-Cas9, as well as the challenges they face. Much has been achieved since the discovery of polymyxins, through several innovative technologies. Nevertheless, colistin resistance mechanisms remains very complex.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
Na Huang ◽  
...  

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.


mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Ibrahim Bitar ◽  
Costas C. Papagiannitsis ◽  
Lucie Kraftova ◽  
Katerina Chudejova ◽  
Vittoria Mattioni Marchetti ◽  
...  

ABSTRACT The aim of this study was to report the characterization of the first mcr-positive Enterobacterales isolated from Czech hospitals. In 2019, one Citrobacter freundii and four Enterobacter isolates were recovered from Czech hospitals. The production of carbapenemases was examined by a matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) imipenem hydrolysis assay. Additionally, bacteria were screened for the presence of carbapenemase-encoding genes and plasmid-mediated colistin resistance genes by PCR. To define the genetic units carrying mcr genes, the genomic DNAs of mcr-carrying clinical isolates were sequenced on the PacBio Sequel I platform. Results showed that all isolates carried blaVIM- and mcr-like genes. Analysis of whole-genome sequencing (WGS) data revealed that all isolates carried mcr-9-like alleles. Furthermore, the three sequence type 106 (ST106) Enterobacter hormaechei isolates harbored the blaVIM-1 gene, while the ST764 E. hormaechei and ST95 C. freundii included blaVIM-4. Analysis of plasmid sequences showed that, in all isolates, mcr-9 was carried on IncHI2 plasmids. Additionally, at least one multidrug resistance (MDR) region was identified in each mcr-9-carrying IncHI2 plasmid. The blaVIM-4 gene was found in the MDR regions of p48880_MCR_VIM and p51929_MCR_VIM. In the three remaining isolates, blaVIM-1 was localized on plasmids (∼55 kb) exhibiting repA-like sequences 99% identical to the respective gene of pKPC-CAV1193. In conclusion, to the best of our knowledge, these 5 isolates were the first mcr-9-positive bacteria of clinical origin identified in the Czech Republic. Additionally, the carriage of the blaVIM-1 on pKPC-CAV1193-like plasmids is described for the first time. Thus, our findings underline the ongoing evolution of mobile elements implicated in the dissemination of clinically important resistance determinants. IMPORTANCE Infections caused by carbapenemase-producing bacteria have led to the revival of polymyxins as the “last-resort” antibiotic. Since 2016, several reports describing the presence of plasmid-mediated colistin resistance genes, mcr, in different host species and geographic areas were published. Here, we report the first detection of Enterobacterales carrying mcr-9-like alleles isolated from Czech hospitals in 2019. Furthermore, the three ST106 Enterobacter hormaechei isolates harbored blaVIM-1, while the ST764 E. hormaechei and ST95 Citrobacter freundii isolates included blaVIM-4. Analysis of WGS data showed that, in all isolates, mcr-9 was carried on IncHI2 plasmids. blaVIM-4 was found in the MDR regions of IncHI2 plasmids, while blaVIM-1 was localized on pKPC-CAV1193-like plasmids, described here for the first time. These findings underline the ongoing evolution of mobile elements implicated in dissemination of clinically important resistance determinants. Thus, WGS characterization of MDR bacteria is crucial to unravel the mechanisms involved in dissemination of resistance mechanisms.


2020 ◽  
Author(s):  
Yang Zhao ◽  
Qiye Wei ◽  
Tianci Chen ◽  
Lijuan Xu ◽  
Jing Liu ◽  
...  

Abstract Background: MicroRNAs (miRNAs) are a class of small non-coding RNAs, which have been demonstrated to play essential roles in plant growth and development, and in responses to abiotic stress. Heat stress is one of the most serious stresses that affecting crop yield and quality, however, the related regulatory mechanisms of miRNAs remains poorly understanding in maize. Results: In this study, a total of 340 miRNAs, including 215 known and 125 novel members, were identified from maize seedlings under heat stress (MH) and control conditions (MC) using high-throughput sequencing approach. The 215 known miRNAs can be further divided into 40 different families, and 21-nt miRNAs were found to be most abundant among the known miRNAs. Thirty-five miRNAs, including 26 known and 9 novel members, were significantly different expressed between MC and MH libraries. Furthermore, 174 target genes were predicted to be cleaved by 115 miRNAs using degradome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for these targets to explore the biological function and pathways involved. Based on the relationships of miRNAs, target genes and the enriched results, a regulatory network was constructed for the miRNAs and their respective target genes, and 16 significantly differently expressed miRNAs (DEMs) were involved in the network. Conclusions: The results revealed novel insights into the roles of miRNAs in heat stress response and provided a useful foundation for understanding the regulatory mechanisms of heat-responsive miRNAs in maize.


2018 ◽  
Vol 108 (2) ◽  
pp. 264-274 ◽  
Author(s):  
Jiang-Kuan Cui ◽  
Huan Peng ◽  
Fen Qiao ◽  
Gao-Feng Wang ◽  
Wen-Kun Huang ◽  
...  

Few molecular details of effectors of Heterodera avenae parasitism are known. We performed a high-throughput sequencing analysis of the H. avenae transcriptome at five developmental stages. A total of 82,549 unigenes were ultimately obtained, and 747 transcripts showed best hits to genes putatively encoding carbohydrate-active enzymes in plant-parasitic nematodes that play an important role in the invasion process. A total of 1,480 unigenes were homologous to known phytonematode effectors, and 63 putative novel effectors were identified in the H. avenae transcriptomes. Twenty-three unigenes were analyzed by qRT-PCR and confirmed to be highly expressed during at least one developmental stage. For in situ hybridization, 17 of the 22 tested putative effectors were specifically expressed and located in the subventral gland cells, and five putative novel effectors were specifically expressed in the dorsal gland. Furthermore, 115 transcripts were found to have putative lethal RNA interference (RNAi) phenotypes. Three target genes with lethal RNAi phenotypes and two of the four tested putative effectors were associated with a decrease in the number of cysts through in vitro RNAi technology. These transcriptomic data lay a foundation for further studies of interactions of H. avenae with cereal and H. avenae parasitic control.


2019 ◽  
Vol 20 (14) ◽  
pp. 3448
Author(s):  
Runqing Yang ◽  
Gu Chen ◽  
Huifeng Peng ◽  
Dong Wei

Coccomyxa subellipsoidea C-169 (C-169) is an oleaginous microalga which is promising for renewable biofuel production. MicroRNAs (miRNAs), as the pivotal modulators of gene expression at post-transcriptional level, are prospective candidates for bioengineering practice. However, so far, no miRNA in C-169 has been reported and its potential impact upon CO2 supplementation remains unclear. High-throughput sequencing of small RNAs from C-169 cultured in air or 2% CO2 revealed 124 miRNAs in total, including 118 conserved miRNAs and six novel ones. In total, 384 genes were predicted as their potential target genes, 320 for conserved miRNAs and 64 for novel miRNAs. The annotated target genes were significantly enriched in six KEGG pathways, including pantothenate and CoA biosynthesis, C5-branched dibasic acid metabolism, 2-oxocarboxylic acid metabolism, butanoate metabolism, valine, leucine and isoleucine biosynthesis and alpha-linolenic acid metabolism. The miRNAs’ target genes were enriched in lipid metabolism as well as RNA-interacting proteins involved in translation, transcription and rRNA processing. The pioneering identification of C-169 miRNAs and analysis of their putative target genes lay the foundation for further miRNA research in eukaryotic algae and will contribute to the development of C-169 as an oleaginous microalga through bioengineering in the future.


Diversity ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 175 ◽  
Author(s):  
Carolina Chiellini ◽  
Sofia Chioccioli ◽  
Alberto Vassallo ◽  
Stefano Mocali ◽  
Elisangela Miceli ◽  
...  

Acquarossa river (Viterbo, Italy) was the site of a prospering Etruscan civilization thanks to metallurgical activity around 625–550 B.C. This caused the spread of heavy metals throughout the area. Rocks along the river probably act as a filter for these elements and they are covered by two different biofilms (epilithons). They differ for both color and bacterial composition. One is red and is enriched with Pseudomonas strains, while the other one is black and Acinetobacter is the most represented genus. Along the river lay the Infernaccio waterfalls, whose surrounding rocks are covered only by the red epilithon. The bacterial composition of this biofilm was analyzed through high throughput sequencing and compared to those ones of red and black epilithons of Acquarossa river. Moreover, cultivable bacteria were isolated and their phenotype (i.e., resistance against antibiotics and heavy metals) was studied. As previously observed in the case of Acquarossa river, characterization of bacterial composition of the Infernaccio red epilithon revealed that the two most represented genera were Acinetobacter and Pseudomonas. Nonetheless, these strains differed from those isolated from Acquarossa, as revealed by RAPD analysis. This work, besides increasing knowledge about the ecological properties of this site, allowed to isolate new bacterial strains, which could potentially be exploited for biotechnological applications, because of their resistance against environmental pollutants.


BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Zilong Zhao ◽  
Dan Liu ◽  
Yanjiao Cui ◽  
Suying Li ◽  
Dan Liang ◽  
...  

Abstract Background Long noncoding RNAs (lncRNAs) have been reported to play critical roles in diverse growth and development processes in plants. However, the systematic identification and characterization of lncRNAs in foxtail millet is nearly blank. Results In this study, we performed high-throughput sequencing of young spikelets from four foxtail millet varieties in different yield levels at booting stage. As a result, a total of 12,378 novel lncRNAs were identified, and 70 were commonly significantly differentially expressed in comparisons between high-yield varieties and conventional varieties, suggesting that they involved in yield formation and regulation in foxtail millet. Functional analysis revealed that among the 70 significantly differentially expressed lncRNAs, 67 could transcriptionally modulate target genes in cis and in trans. Moreover, 18 lncRNAs related to grain yield in foxtail millet were predicted to function as miRNA target mimics and regulate gene expression by competing for the interaction between miRNAs and their target mRNAs. Conclusion Our results will provide materials for elucidation of the molecular mechanisms of lncRNAs participate in yield regulation, and will contribute to high yield foxtail millet breeding.


2021 ◽  
Author(s):  
Bohan Ma ◽  
Yue Li ◽  
Mohamed Khalifa ◽  
Meng Teng ◽  
Aijing Zhang ◽  
...  

Abstract Background: Long non-coding RNAs (lncRNAs) are non-coding RNAs of more than 200 nucleotides. To date, the roles of lncRNAs in soybean fatty acid synthesis have not been fully studied. Here, the low-linolenic acid ‘mutant 72’ (MT72) and the wild-type control ‘JiNong 18’(JN18) were used. Based on the previously published data on lncRNAs related RNA-seq in young pods of soybean 30 d to 40 d after flowering, lncRNAs and mRNAs from soybean pods 50 d after flowering were identified using high-throughput sequencing. The possible target genes of lncRNAs were predicted, and the functions related to fatty acid synthesis were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Results: A total of 10,500 lncRNAs and 54,370 mRNAs were identified, and 115 possible target genes of 1,805 differentially expressed lncRNAs were found to be involved in fatty acid synthesis. A network of lncRNAs and mRNAs was constructed, and a total of 604 lncRNAs and 1,484 mRNAs had regulatory relationships. Among them, 115 target genes of 77 lncRNAs were directly or indirectly involved in fatty acid biosynthesis.Conclusions: The function related to fatty acid synthesis was predicted by differential expression of the target gene mRNAs interacting with lncRNAs. In conclusion, our results provide a theoretical basis for studies on fatty acid synthesis of lncRNAs in soybean.


2013 ◽  
Vol 22 (3-4) ◽  
pp. 255-277 ◽  
Author(s):  
Vladimír Bačík ◽  
Michal Klobučník

Abstract The Tour de France, a three week bicycle race has a unique place in the world of sports. The 100th edition of the event took place in 2013. In the past of 110 years of its history, people noticed unique stories and duels in particular periods, celebrities that became legends that the world of sports will never forget. Also many places where the races unfolded made history in the Tour de France. In this article we tried to point out the spatial context of this event using advanced technologies for distribution of historical facts over the Internet. The Introduction briefly displays the attendance of a particular stage based on a regional point of view. The main topic deals with selected historical aspects of difficult ascents which every year decide the winner of Tour de France, and also attract fans from all over the world. In the final stage of the research, the distribution of results on the website available to a wide circle of fans of this sports event played a very significant part (www.tdfrance.eu). Using advanced methods and procedures we have tried to capture the historical and spatial dimensions of Tour de France in its general form and thus offering a new view of this unique sports event not only to the expert community, but for the general public as well.


2020 ◽  
Vol 10 (4) ◽  
pp. 93-97
Author(s):  
Anil Kumar A ◽  
Raja Sheker K ◽  
Naveen B ◽  
Abhilash G ◽  
Akila CR

Seas assets that give us a variety of characteristic items to control bacterial, contagious and viral ailment and mostly utilized for malignancy chemotherapy practically from spineless creatures, for example, bryozoans, wipes, delicate corals, coelenterates, ocean fans, ocean bunnies, molluscs and echinoderms. In the previous 30 - 40 years, marine plants and creatures have been the focal point of overall endeavours to characterize the regular results of the marine condition. Numerous marine characteristic items have been effectively exceptional to the last phases of clinical preliminaries, including dolastatin-10, a group of peptides disengaged from Indian ocean rabbit, Dollabella auricularia. Ecteinascidin-743 from mangrove tunicate Ecteinascidia turbinata, Didemnins was isolated from Caribbean tunicate Trididemnum solidum and Conopeptides from cone snails (Conus sp.), and a developing number of up-and-comers have been chosen as promising leads for expanded pre-clinical appraisals. Sea anemones possess numerous tentacles containing stinging cells or cnidocytes. The stinging cells are equipped with small organelles known as nematocysts. The two species of sea anemones namely, Heteractis magnificaandStichodactyla haddoni, were collected from Mandapam coastal waters of Ramanathapuram district, Tamilnadu, India. The Nematocyst was collected and centrifuged, and the supernatant was lyophilized and stored for further analysis. The amount of protein from Heteractis Magnifica and Stichodactyla haddoni was estimated. The crude extract has shown haemolytic activity on chicken blood and goat blood. In the antibacterial activity of the sea anemone against six bacterial strains Staphylococcus aureus, Salmonella typhii, Salmonella paratyphii, Klebsiella pneumonia, Vibrio cholerae, Pseudomonas aeruginosa. Antibacterial activity of H. Magnifica and S.haddoni was measured as the radius of the zone of inhibition.


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