SUMMARY Strains of bacteria resistant to antibiotics, particularly those that are multiresistant, are an increasing major health care problem around the world. It is now abundantly clear that both Gram-negative and Gram-positive bacteria are able to meet the evolutionary challenge of combating antimicrobial chemotherapy, often by acquiring preexisting resistance determinants from the bacterial gene pool. This is achieved through the concerted activities of mobile genetic elements able to move within or between DNA molecules, which include insertion sequences, transposons, and gene cassettes/integrons, and those that are able to transfer between bacterial cells, such as plasmids and integrative conjugative elements. Together these elements play a central role in facilitating horizontal genetic exchange and therefore promote the acquisition and spread of resistance genes. This review aims to outline the characteristics of the major types of mobile genetic elements involved in acquisition and spread of antibiotic resistance in both Gram-negative and Gram-positive bacteria, focusing on the so-called ESKAPEE group of organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli), which have become the most problematic hospital pathogens.

https://cmr.asm.org/content/cmr/31/4/e00088-17.full-text.pdf

Mobile Genetic Elements Associated with Antimicrobial Resistance

Insertion sequences (ISs), arguably the smallest and most numerous autonomous transposable elements (TEs), are important players in shaping their host genomes This review focuses on prokaryotic ISs We discuss IS distribution and impact on genome evolution We also examine their effects on gene expression, especially their role in activating neighbouring genes, a phenomenon of particular importance in the recent upsurge of bacterial antibiotic resistance We explain how ISs are identified and classified into families by a combination of characteristics including their transposases (Tpases), their overall genetic organisation and the accessory genes which some ISs carry We then describe the organisation of autonomous and nonautonomous IS-related elements This is used to illustrate the growing recognition that the boundaries between different types of mobile element are becoming increasingly difficult to define as more are being identified We review the known Tpase types, their different catalytic activities used in cleaving and rejoining DNA strands during transposition, their organisation into functional domains and the role of this in regulation Finally, we consider examples of prokaryotic IS domestication In a more speculative section, we discuss the necessity of constructing more quantitative dynamic models to fully appreciate the continuing impact of TEs on prokaryotic populations

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/1574-6976.12067

Bacterial insertion sequences: their genomic impact and diversity

Horizontal gene transfer plays a major role in microbial evolution, allowing microbes to acquire new genes and phenotypes. Integrative and conjugative elements (ICEs, a.k.a. conjugative transposons) are modular mobile genetic elements integrated into a host genome and are passively propagated during chromosomal replication and cell division. Induction of ICE gene expression leads to excision, production of the conserved conjugation machinery (a type IV secretion system), and the potential to transfer DNA to appropriate recipients. ICEs typically contain cargo genes that are not usually related to the ICE life cycle and that confer phenotypes to host cells. We summarize the life cycle and discovery of ICEs, some of the regulatory mechanisms, and how the types of cargo have influenced our view of ICEs. We discuss how ICEs can acquire new cargo genes and describe challenges to the field and various perspectives on ICE biology.

Integrative and Conjugative Elements (ICEs): What They Do and How They Work

Massive expansion of human gut bacteriophage diversity

ICEberg 2.0 (http://db-mml.sjtu.edu.cn/ICEberg/) is an updated database that provides comprehensive information about bacterial integrative and conjugative elements (ICEs). Compared with the previous version, three major improvements were made. First, with the aid of text mining and manual curation, it now recorded the details of 1032 ICEs, including 270 with experimental supports and 762 from bioinformatics prediction. Second, as increasing evidence has shown that ICEs frequently mobilize the so-called ‘hitchhikers’, such as integrative and mobilizable elements (IMEs) and cis-mobilizable elements (CIMEs), 83 known transfer interactions between 49 IMEs and 7 CIMEs with 19 ICEs taken from the literature were included and illustrated with visually intuitive directed graphs. An expanded collection of 260 chromosome-borne IMEs and 235 CIMEs was also added. At last, ICEberg 2.0 provides an online tool ICEfinder to predict ICEs or IMEs in bacterial genome sequences. It combines a similarity search for the integrase, relaxase and/or type IV secretion system and the co-localization of these corresponding homologous genes. With the recent updates, ICEberg 2.0 might provide better support for understanding the biological traits of ICEs, especially as their interaction with cognate mobilizable elements may further promote horizontal gene flow.

/pdf/iceberg-2-0-an-updated-database-of-bacterial-integrative-and-1wmqy431rw.pdf

ICEberg 2.0: an updated database of bacterial integrative and conjugative elements.

TADB2.0 (http://bioinfo-mml.sjtu.edu.cn/TADB2/) is an updated database that provides comprehensive information about bacterial type II toxin-antitoxin (TA) loci. Compared with the previous version, the database refined and the new data schema is employed. With the aid of text mining and manual curation, it recorded 6193 type II TA loci in 870 replicons of bacteria and archaea, including 105 experimentally validated TA loci. In addition, the newly developed tool TAfinder combines the homolog searches and the operon structure detection, allowing the prediction for type II TA pairs in bacterial genome sequences. It also helps to investigate the genomic context of predicted TA loci for putative virulence factors, antimicrobial resistance determinants and mobile genetic elements via alignments to the specific public databases. Additionally, the module TAfinder-Compare allows comparing the presence of the given TA loci across the close relative genomes. With the recent updates, TADB2.0 might provide better support for understanding the important roles of type II TA systems in the prokaryotic life activities.

TADB 2.0: an updated database of bacterial type II toxin–antitoxin loci

ICEberg (http://db-mml.sjtu.edu.cn/ICEberg/) is an integrated database that provides comprehensive information about integrative and conjugative elements (ICEs) found in bacteria. ICEs are conjugative self-transmissible elements that can integrate into and excise from a host chromosome. An ICE contains three typical modules, integration and excision, conjugation, and regulation modules, that collectively promote vertical inheritance and periodic lateral gene flow. Many ICEs carry likely virulence determinants, antibiotic-resistant factors and/or genes coding for other beneficial traits. ICEberg offers a unique, highly organized, readily explorable archive of both predicted and experimentally supported ICE-relevant data. It currently contains details of 428 ICEs found in representatives of 124 bacterial species, and a collection of >400 directly related references. A broad range of similarity search, sequence alignment, genome context browser, phylogenetic and other functional analysis tools are readily accessible via ICEberg. We propose that ICEberg will facilitate efficient, multi-disciplinary and innovative exploration of bacterial ICEs and be of particular interest to researchers in the broad fields of prokaryotic evolution, pathogenesis, biotechnology and metabolism. The ICEberg database will be maintained, updated and improved regularly to ensure its ongoing maximum utility to the research community.

/pdf/iceberg-a-web-based-resource-for-integrative-and-conjugative-ieppk2h4ih.pdf

ICEberg: a web-based resource for integrative and conjugative elements found in Bacteria

Klebsiella pneumoniae is an increasingly important bacterial pathogen to human. This Gram-negative bacterium species has become a serious concern due to its dramatic increase in the levels of multiple antibiotic resistances, particularly to carbapenems. The toxin-antitoxin (TA) system has recently been reported to be involved in the formation of drug-tolerant persister cells. The type II TA system is composed of a stable toxin protein and a relatively unstable antitoxin protein that is able to inhibit the toxin. Here, we examine the type II TA locus distribution and compare the TA diversity throughout ten completely sequenced K. pneumoniae genomes by using bioinformatics approaches. Two hundred and twelve putative type II TA loci were identified in 30 replicons of these K. pneumoniae strains. The amino acid sequence similarity-based grouping shows that these loci distribute differently not only among different K. pneumoniae strains isolated from diverse sources, but also between their chromosomes and plasmids.

Prediction of Type II Toxin-Antitoxin Loci in Klebsiella pneumoniae Genome Sequences

The web-based database TADB offers a comprehensive compilation of both predicted and experimentally supported type II toxin-antitoxin (TA) locus data and genetic features. Here, we examine the distribution and diversity of TADB-recorded TA loci throughout bacterial and archaeal genomes; in particular, those carried by the chromosomal mobile elements, such as prophages and integrative and conjugative elements (ICEs). Then the discussion covers the toxin protein-based TA family classification and the conserved domain pairs found in TA proteins.

Type II Toxin-Antitoxin Loci: Phylogeny

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Papers

TADB 2.0: an updated database of bacterial type II toxin–antitoxin loci

ICEberg: a web-based resource for integrative and conjugative elements found in Bacteria

Prediction of Type II Toxin-Antitoxin Loci in Klebsiella pneumoniae Genome Sequences

Type II Toxin-Antitoxin Loci: Phylogeny