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917300.9551Bacterial defences: mechanisms, evolution and antimicrobial resistance. Throughout their evolutionary history, bacteria have faced diverse threats from other microorganisms, including competing bacteria, bacteriophages and predators. In response to these threats, they have evolved sophisticated defence mechanisms that today also protect bacteria against antibiotics and other therapies. In this Review, we explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. We also review the countermeasures that attackers have evolved to overcome bacterial defences. We argue that understanding how bacteria defend themselves in nature is important for the development of new therapies and for minimizing resistance evolution.202337095190
923910.9550Tragedy of the commons among antibiotic resistance plasmids. As social interactions are increasingly recognized as important determinants of microbial fitness, sociobiology is being enlisted to better understand the evolution of clinically relevant microbes and, potentially, to influence their evolution to aid human health. Of special interest are situations in which there exists a "tragedy of the commons," where natural selection leads to a net reduction in fitness for all members of a population. Here, I demonstrate the existence of a tragedy of the commons among antibiotic resistance plasmids of bacteria. In serial transfer culture, plasmids evolved a greater ability to superinfect already-infected bacteria, increasing plasmid fitness when evolved genotypes were rare. Evolved plasmids, however, fell victim to their own success, reducing the density of their bacterial hosts when they became common and suffering reduced fitness through vertical transmission. Social interactions can thus be an important determinant of evolution for the molecular endosymbionts of bacteria. These results also identify an avenue of evolution that reduces proliferation of both antibiotic resistance genes and their bacterial hosts.201222486703
964320.9543Introducing the sporobiota and sporobiome. Unrelated spore-forming bacteria share unique characteristics stemming from the presence of highly resistant endospores, leading to similar challenges in health and disease. These characteristics are related to the presence of these highly transmissible spores, which are commonly spread within the environment and are implicated in host-to-host transmission. In humans, spore-forming bacteria contribute to a variety of pathological processes that share similar characteristics, including persistence, chronicity, relapses and the maintenance of the resistome. We first outline the necessity of characterizing the totality of the spore-forming bacteria as the sporobiota based on their unique common characteristics. We further propose that the collection of all genes of spore-forming bacteria be known as the sporobiome. Such differentiation is critical for exploring the cross-talk between the sporobiota and other members of the gut microbiota, and will allow for a better understanding of the implications of the sporobiota and sporobiome in a variety of pathologies and the spread of antibiotic resistance.201728680484
10830.9543RtcB2-PrfH Operon Protects E. coli ATCC25922 Strain from Colicin E3 Toxin. In the bid to survive and thrive in an environmental setting, bacterial species constantly interact and compete for resources and space in the microbial ecosystem. Thus, they have adapted to use various antibiotics and toxins to fight their rivals. Simultaneously, they have evolved an ability to withstand weapons that are directed against them. Several bacteria harbor colicinogenic plasmids which encode toxins that impair the translational apparatus. One of them, colicin E3 ribotoxin, mediates cleavage of the 16S rRNA in the decoding center of the ribosome. In order to thrive upon deployment of such ribotoxins, competing bacteria may have evolved counter-conflict mechanisms to prevent their demise. A recent study demonstrated the role of PrfH and the RtcB2 module in rescuing a damaged ribosome and the subsequent re-ligation of the cleaved 16S rRNA by colicin E3 in vitro. The rtcB2-prfH genes coexist as gene neighbors in an operon that is sporadically spread among different bacteria. In the current study, we report that the RtcB2-PrfH module confers resistance to colicin E3 toxicity in E. coli ATCC25922 cells in vivo. We demonstrated that the viability of E. coli ATCC25922 strain that is devoid of rtcB2 and prfH genes is impaired upon action of colicin E3, in contrast to the parental strain which has intact rtcB2 and prfH genes. Complementation of the rtcB2 and prfH gene knockout with a high copy number-plasmid (encoding either rtcB2 alone or both rtcB2-prfH operon) restored resistance to colicin E3. These results highlight a counter-conflict system that may have evolved to thwart colicin E3 activity.202235742896
410440.9542Human intestinal bacteria as reservoirs for antibiotic resistance genes. Human intestinal bacteria have many roles in human health, most of which are beneficial or neutral for the host. In this review, we explore a more sinister side of intestinal bacteria; their role as traffickers in antibiotic resistance genes. Evidence is accumulating to support the hypothesis that intestinal bacteria not only exchange resistance genes among themselves but might also interact with bacteria that are passing through the colon, causing these bacteria to acquire and transmit antibiotic resistance genes.200415337162
917250.9541These Are the Genes You're Looking For: Finding Host Resistance Genes. Humanity's ongoing struggle with new, re-emerging and endemic infectious diseases serves as a frequent reminder of the need to understand host-pathogen interactions. Recent advances in genomics have dramatically advanced our understanding of how genetics contributes to host resistance or susceptibility to bacterial infection. Here we discuss current trends in defining host-bacterial interactions at the genome-wide level, including screens that harness CRISPR/Cas9 genome editing, natural genetic variation, proteomics, and transcriptomics. We report on the merits, limitations, and findings of these innovative screens and discuss their complementary nature. Finally, we speculate on future innovation as we continue to progress through the postgenomic era and towards deeper mechanistic insight and clinical applications.202133004258
818360.9541Modification of arthropod vector competence via symbiotic bacteria. Some of the world's most devastating diseases are transmitted by arthropod vectors. Attempts to control these arthropods are currently being challenged by the widespread appearance of insecticide resistance. It is therefore desirable to develop alternative strategies to complement existing methods of vector control. In this review, Charles Beard, Scott O'Neill, Robert Tesh, Frank Richards and Serap Aksoy present an approach for introducing foreign genes into insects in order to confer refractoriness to vector populations, ie. the inability to transmit disease-causing agents. This approach aims to express foreign anti-parasitic or anti-viral gene products in symbiotic bacteria harbored by insects. The potential use of naturally occurring symbiont-based mechanisms in the spread of such refractory phenotypes is also discussed.199315463748
835970.9541Comparative Genomic Analysis of Acanthamoeba Endosymbionts Highlights the Role of Amoebae as a "Melting Pot" Shaping the Rickettsiales Evolution. Amoebae have been considered as a genetic "melting pot" for its symbionts, facilitating genetic exchanges of the bacteria that co-inhabit the same host. To test the "melting pot" hypothesis, we analyzed six genomes of amoeba endosymbionts within Rickettsiales, four of which belong to Holosporaceae family and two to Candidatus Midichloriaceae. For the first time, we identified plasmids in obligate amoeba endosymbionts, which suggests conjugation as a potential mechanism for lateral gene transfers (LGTs) that underpin the "melting pot" hypothesis. We found strong evidence of recent LGTs between the Rickettsiales amoeba endosymbionts, suggesting that the LGTs are continuous and ongoing. In addition, comparative genomic and phylogenomic analyses revealed pervasive and recurrent LGTs between Rickettsiales and distantly related amoeba-associated bacteria throughout the Rickettsiales evolution. Many of these exchanged genes are important for amoeba-symbiont interactions, including genes in transport system, antibiotic resistance, stress response, and bacterial virulence, suggesting that LGTs have played important roles in the adaptation of endosymbionts to their intracellular habitats. Surprisingly, we found little evidence of LGTs between amoebae and their bacterial endosymbionts. Our study strongly supports the "melting pot" hypothesis and highlights the role of amoebae in shaping the Rickettsiales evolution.201729177480
958380.9541Bacteriophages presence in nature and their role in the natural selection of bacterial populations. Phages are the obligate parasite of bacteria and have complex interactions with their hosts. Phages can live in, modify, and shape bacterial communities by bringing about changes in their abundance, diversity, physiology, and virulence. In addition, phages mediate lateral gene transfer, modify host metabolism and reallocate bacterially-derived biochemical compounds through cell lysis, thus playing an important role in ecosystem. Phages coexist and coevolve with bacteria and have developed several antidefense mechanisms in response to bacterial defense strategies against them. Phages owe their existence to their bacterial hosts, therefore they bring about alterations in their host genomes by transferring resistance genes and genes encoding toxins in order to improve the fitness of the hosts. Application of phages in biotechnology, environment, agriculture and medicines demands a deep insight into the myriad of phage-bacteria interactions. However, to understand their complex interactions, we need to know how unique phages are to their bacterial hosts and how they exert a selective pressure on the microbial communities in nature. Consequently, the present review focuses on phage biology with respect to natural selection of bacterial populations.202033170167
971990.9539Dynamics of antibiotic resistance genes in plasmids and bacteriophages. This brief review explores the intricate interplay between bacteriophages and plasmids in the context of antibiotic resistance gene (ARG) dissemination. Originating from studies in the late 1950s, the review traces the evolution of knowledge regarding extrachromosomal factors facilitating horizontal gene transfer and adaptation in bacteria. Analyzing the gene repertoires of plasmids and bacteriophages, the study highlights their contributions to bacterial evolution and adaptation. While plasmids encode essential and accessory genes influencing host characteristics, bacteriophages carry auxiliary metabolic genes (AMGs) that augment host metabolism. The debate on phages carrying ARGs is explored through a critical evaluation of various studies, revealing contrasting findings from researchers. Additionally, the review addresses the interplay between prophages and plasmids, underlining their similarities and divergences. Based on the available literature evidence, we conclude that plasmids generally encode ARGs while bacteriophages typically do not contain ARGs. But extra-chromosomaly present prophages with plasmid characteristics can encode and disseminate ARGs.202538651513
8137100.9538Modulation of Bacterial Fitness and Virulence Through Antisense RNAs. Regulatory RNAs contribute to gene expression control in bacteria. Antisense RNAs (asRNA) are a class of regulatory RNAs that are transcribed from opposite strands of their target genes. Typically, these untranslated transcripts bind to cognate mRNAs and rapidly regulate gene expression at the post-transcriptional level. In this article, we review asRNAs that modulate bacterial fitness and increase virulence. We chose examples that underscore the variety observed in nature including, plasmid- and chromosome-encoded asRNAs, a riboswitch-regulated asRNA, and asRNAs that require other RNAs or RNA-binding proteins for stability and activity. We explore how asRNAs improve bacterial fitness and virulence by modulating plasmid acquisition and maintenance, regulating transposon mobility, increasing resistance against bacteriophages, controlling flagellar production, and regulating nutrient acquisition. We conclude with a brief discussion on how this knowledge is helping to inform current efforts to develop new therapeutics.202033747974
9581110.9538Lateral gene transfer, bacterial genome evolution, and the Anthropocene. Lateral gene transfer (LGT) has significantly influenced bacterial evolution since the origins of life. It helped bacteria generate flexible, mosaic genomes and enables individual cells to rapidly acquire adaptive phenotypes. In turn, this allowed bacteria to mount strong defenses against human attempts to control their growth. The widespread dissemination of genes conferring resistance to antimicrobial agents has precipitated a crisis for modern medicine. Our actions can promote increased rates of LGT and also provide selective forces to fix such events in bacterial populations. For instance, the use of selective agents induces the bacterial SOS response, which stimulates LGT. We create hotspots for lateral transfer, such as wastewater systems, hospitals, and animal production facilities. Conduits of gene transfer between humans and animals ensure rapid dissemination of recent transfer events, as does modern transport and globalization. As resistance to antibacterial compounds becomes universal, there is likely to be increasing selection pressure for phenotypes with adverse consequences for human welfare, such as enhanced virulence, pathogenicity, and transmission. Improved understanding of the ecology of LGT could help us devise strategies to control this fundamental evolutionary process.201727706829
9478120.9537General principles of antibiotic resistance in bacteria. Given the impact of antibiotic resistance on human health, its study is of great interest from a clinical view- point. In addition, antibiotic resistance is one of the few examples of evolution that can be studied in real time. Knowing the general principles involved in the acquisition of antibiotic resistance is therefore of interest to clinicians, evolutionary biologists and ecologists. The origin of antibiotic resistance genes now possessed by human pathogens can be traced back to environmental microorganisms. Consequently, a full understanding of the evolution of antibiotic resistance requires the study of natural environments as well as clinical ecosystems. Updated information on the evolutionary mechanisms behind resistance, indicates that ecological connectivity, founder effect and fitness costs are important bottle- necks that modulate the transfer of resistance from environmental microorganisms to pathogens.201424847651
8327130.9537'Big things in small packages: the genetics of filamentous phage and effects on fitness of their host'. This review synthesizes recent and past observations on filamentous phages and describes how these phages contribute to host phentoypes. For example, the CTXφ phage of Vibrio cholerae encodes the cholera toxin genes, responsible for causing the epidemic disease, cholera. The CTXφ phage can transduce non-toxigenic strains, converting them into toxigenic strains, contributing to the emergence of new pathogenic strains. Other effects of filamentous phage include horizontal gene transfer, biofilm development, motility, metal resistance and the formation of host morphotypic variants, important for the biofilm stress resistance. These phages infect a wide range of Gram-negative bacteria, including deep-sea, pressure-adapted bacteria. Many filamentous phages integrate into the host genome as prophage. In some cases, filamentous phages encode their own integrase genes to facilitate this process, while others rely on host-encoded genes. These differences are mediated by different sets of 'core' and 'accessory' genes, with the latter group accounting for some of the mechanisms that alter the host behaviours in unique ways. It is increasingly clear that despite their relatively small genomes, these phages exert signficant influence on their hosts and ultimately alter the fitness and other behaviours of their hosts.201525670735
8625140.9537Marine viruses: truth or dare. Over the past two decades, marine virology has progressed from a curiosity to an intensely studied topic of critical importance to oceanography. At concentrations of approximately 10 million viruses per milliliter of surface seawater, viruses are the most abundant biological entities in the oceans. The majority of these viruses are phages (viruses that infect bacteria). Through lysing their bacterial hosts, marine phages control bacterial abundance, affect community composition, and impact global biogeochemical cycles. In addition, phages influence their hosts through selection for resistance, horizontal gene transfer, and manipulation of bacterial metabolism. Recent work has also demonstrated that marine phages are extremely diverse and can carry a variety of auxiliary metabolic genes encoding critical ecological functions. This review is structured as a scientific "truth or dare," revealing several well-established "truths" about marine viruses and presenting a few "dares" for the research community to undertake in future studies.201222457982
9580150.9536Antibiotic resistance in bacterial communities. Bacteria are single-celled organisms, but the survival of microbial communities relies on complex dynamics at the molecular, cellular, and ecosystem scales. Antibiotic resistance, in particular, is not just a property of individual bacteria or even single-strain populations, but depends heavily on the community context. Collective community dynamics can lead to counterintuitive eco-evolutionary effects like survival of less resistant bacterial populations, slowing of resistance evolution, or population collapse, yet these surprising behaviors are often captured by simple mathematical models. In this review, we highlight recent progress - in many cases, advances driven by elegant combinations of quantitative experiments and theoretical models - in understanding how interactions between bacteria and with the environment affect antibiotic resistance, from single-species populations to multispecies communities embedded in an ecosystem.202337054512
9712160.9536Diverse events have transferred genes for edible seaweed digestion from marine to human gut bacteria. Humans harbor numerous species of colonic bacteria that digest fiber polysaccharides in commonly consumed terrestrial plants. More recently in history, regional populations have consumed edible macroalgae seaweeds containing unique polysaccharides. It remains unclear how extensively gut bacteria have adapted to digest these nutrients. Here, we show that the ability of gut bacteria to digest seaweed polysaccharides is more pervasive than previously appreciated. Enrichment-cultured Bacteroides harbor previously discovered genes for seaweed degradation, which have mobilized into several members of this genus. Additionally, other examples of marine bacteria-derived genes, and their mobile DNA elements, are involved in gut microbial degradation of seaweed polysaccharides, including genes in gut-resident Firmicutes. Collectively, these results uncover multiple separate events that have mobilized the genes encoding seaweed-degrading-enzymes into gut bacteria. This work further underscores the metabolic plasticity of the human gut microbiome and global exchange of genes in the context of dietary selective pressures.202235240043
9589170.9536Phage Therapy: Going Temperate? Strictly lytic phages have been consensually preferred for phage therapy purposes. In contrast, temperate phages have been avoided due to an inherent capacity to mediate transfer of genes between bacteria by specialized transduction - an event that may increase bacterial virulence, for example, by promoting antibiotic resistance. Now, advances in sequencing technologies and synthetic biology are providing new opportunities to explore the use of temperate phages for therapy against bacterial infections. By doing so we can considerably expand our armamentarium against the escalating threat of antibiotic-resistant bacteria.201930466900
6654180.9536Natural recreational waters and the risk that exposure to antibiotic resistant bacteria poses to human health. Antimicrobial resistance (AMR) is widely recognised as a considerable threat to human health, wellbeing and prosperity. Many clinically important antibiotic resistance genes are understood to have originated in the natural environment. However, the complex interactions between humans, animals and the environment makes the health implications of environmental AMR difficult to quantify. This narrative review focuses on the current state of knowledge regarding antibiotic resistant bacteria (ARB) in natural bathing waters and implications for human health. It considers the latest research focusing on the transmission of ARB from bathing waters to humans. The limitations of existing evidence are discussed, as well as research priorities. The authors are of the opinion that future studies should include faecally contaminated bathing waters and people exposed to these environments to accurately parameterise environment-to-human transmission.202234739925
6791190.9535Microplastics in marine pollution: Oceanic hitchhikers for the global dissemination of antimicrobial-resistant bacteria. Microplastics (MPs) are globally anthropogenic contaminants of marine environments. Bacteria can colonize MPs forming biofilms that constitute the plastisphere. Carbapenem-resistant bacteria in plastisphere could be a hidden threat for marine life. The role of MPs in the spread of AMR bacteria/genes deserves global investigation.202540469541