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New Strategies to Discover Non-Ribosomal Peptides as a Source of Antibiotics Molecules
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Mario Alberto Martínez-Núñez, Zuemy Rodríguez-Escamilla, Víctor López y López
The antibiotic resistance has always been present in bacteria, even before the use of antibiotics as a medical molecule. Antibiotic resistance is common in contemporary and ancient environmental bacteria, and the genes associated to this phenotype are similar to those present in pathogens (Pawlowski et al., 2016). Antibiotic resistance is acquired either through mutations or by horizontal gene transfer of resistance related genes (Martinez and Baquero, 2000; Furusawa et al., 2018). However, since the 1940s, the use of antibiotics has been transformed as one of the main evolutionary forces driving antibiotic resistance through a selection of mobile elements that have incremented the resistance capacity of both pathogenic and non-pathogenic bacteria, acquiring a variety of elements that conferred redundant protection against individual antibiotics (Fisher et al., 2005; Pawlowski et al., 2016). The indiscriminate use of antibiotics to treat infections in human and animals, for growth promotion in animals, aquaculture or agricultural production, suggests that a substantial fraction of diverse antibiotics ends up in the environment such as wastewater, sludge, soil, river water and others; where bacteria are exposed for long periods of time to low concentrations of diverse antibiotics that are presents due of anthropogenic activities (Wistrand-Yuen et al., 2018). Additionally, clinical doses of diverse antibiotics offer selective benefits to naturally occurring resistant bacteria, resulting in evolutionary dynamics of antibiotic resistance (Furusawa et al., 2018).
Mobile DNA Sequences and Their Possible Role in Evolution
Published in S. K. Dutta, DNA Systematics, 2019
Georgii P. Georgiev, Yurii V. Ilyin, Alexei P. Ryskov, Tatiana I. Gerasimova
Amplification of mobile elements themselves increases the amount of genetic material in the genome. This extra material may be used for the formation of new genes in evolution. We have already mentioned that almost any part of the genome may act as a passive transposable element mobilized through reverse transcription of RNA-polymerase II or III transcripts. Such novel construction may appear in any region of the genome. In this way, the complete genes, their parts, larger sequences of DNA, or small signal sequences can be spread throughout the genome. As a result, new genes or some novel constructions consisting of parts of different genes or of their regulatory elements can appear.
Engineering Escherichia coli to Combat Cancer
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
Carlos Piñero-Lambea, David Ruano-Gallego, Gustavo Bodelón, Beatriz Álvarez, Luis Ángel Fernández
The projected synthetic injector E. coli (SIEC) strain would have integrated in the bacterial chromosome all genes required for the assembly of EPEC injectisomes under the control of an inducible promoter, such as the Ptac, which can be induced with isopropyl-β-d-1-thiogalactopyranoside (IPTG) [99] (Fig. 7.4A). In our approach, gene integration was conducted by a markerless strategy [62] used previously for integration of SAs and lux operon [38]. This strategy renders the resulting engineered bacteria free of antibiotic resistance genes and mobile elements (i.e., plasmids) and allows a stable, controlled expression of the injectisomes.
Bacterial death from treatment with fluoroquinolones and other lethal stressors
Published in Expert Review of Anti-infective Therapy, 2021
Antimicrobial agents have two general activities: they block pathogen growth and, in many cases, they also kill pathogens. For curing most common infections, bacteriostatic antimicrobials are considered as effective as lethal ones [1], largely because host defense systems clear pathogens when their growth is blocked. Lethal activity is often viewed as unnecessary for cure, except with immune-suppressed patients and with a few serious diseases involving immune-privileged sites. Indeed, inhibition of growth, not killing, is the accepted measure of antimicrobial activity [2]. However, simply curing most infections is inadequate from a public health perspective, because the approach has been accompanied by widespread antimicrobial resistance. Part of the reason is that antimicrobial concentrations sufficient to cure often enrich resistant mutant subpopulations [3,4]. Although mutant subpopulations may be small and infections are usually cleared, antimicrobial consumption is so large that expansion of resistant subpopulations is significant, especially after resistance genes enter mobile elements. Moreover, some antimicrobials, such as the quinolones, are themselves mutagenic [5,6], thereby creating resistant subpopulations. Managing antimicrobial use in the Era of Antibiotic Resistance requires rapid killing of pathogens to suppress the emergence of resistance and clear infections. Antimicrobial management can also involve limiting lethal action, particularly to preserve the gut microbiome during antimicrobial treatment. Thus, knowledge of the death process is central to manipulating bacterial populations.
Parabacteroides distasonis: intriguing aerotolerant gut anaerobe with emerging antimicrobial resistance and pathogenic and probiotic roles in human health
Published in Gut Microbes, 2021
Jessica C. Ezeji, Daven K. Sarikonda, Austin Hopperton, Hailey L. Erkkila, Daniel E. Cohen, Sandra P. Martinez, Fabio Cominelli, Tomomi Kuwahara, Armand E. K. Dichosa, Caryn E. Good, Michael R. Jacobs, Mikhail Khoretonenko, Alida Veloo, Alexander Rodriguez-Palacios
According to phylogenetic analyses, P. distasonis diverged from a common ancestor shared with Bacteroides species, as confirmed via nucleotide sequencing of the complete 16S rRNA gene from distinct bacterial species.37 A study by Xu et al.37 explored the driving forces behind the adaptation of Bacteroidetes in the distal gut environment and their importance to the evolution of human gut commensals. To examine how the intestinal environment affects microbial genome evolution, Xu et al.37 sequenced the genomes of two members of the distal human gut microbiota, B. vulgatus and P. distasonis. Through comparison with other sequenced gut and non-gut Bacteroidetes, and analyzing their niches and habitat adaptations, Xu et al. identified three general functions that could illustrate an evolutionary uniqueness for the Bacteroidetes phylum: polysaccharide metabolism, environmental sensing and gene regulation, and membrane transport. These processes are important in aiding with lateral gene transfer, mobile elements, and gene amplification, all of which affect the ability of gut-dwelling Bacteroidetes to vary their cell surface, sense their environment, and harvest nutrients present in the distal colon.37 More recently, genome-based analyses have examined the metabolic features that are typical for a wide array of Bacteroides, which complements the taxonomic classification of the phylumspecies within.38–40
Systematic review of human gut resistome studies revealed variable definitions and approaches
Published in Gut Microbes, 2020
Jeffery Ho, Yun Kit Yeoh, Nilakshi Barua, Zigui Chen, Grace Lui, Sunny H Wong, Xiao Yang, Martin CW Chan, Paul KS Chan, Peter M Hawkey, Margaret Ip
The use of metagenomic shotgun sequencing circumvents the problem of non-culturable gut commensals.52–54 The results are often limited by the bioinformatics pipelines and ARG database(s) selected for analyses. Recently, the National Center for Biotechnology Information (NCBI) produced a high-quality, curated, AMR gene reference database consisting of up-to-date protein and gene nomenclature. A comparison of the susceptibilities of three common Gram-negative foodborne pathogens against the database gave high consistent predictions of 98.4%. This database is designated as AMRFinder with more than 390,000 entries, which is one of the most comprehensive databases.50 However, the small size of the contigs which are assembled renders the characterization of the resistance-gene harboring transposons or other mobile elements difficult.21 This can be overcome by constructing and screening of fosmid libraries using longer DNA fragments isolated from pulsed-field gel electrophoresis assuming that the gene encodes the same phenotype in both the heterologous host and the native bacterium.8