# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8337 | 0 | 0.9960 | Dynamic Boolean modelling reveals the influence of energy supply on bacterial efflux pump expression. Antimicrobial resistance (AMR) is a global health issue. One key factor contributing to AMR is the ability of bacteria to export drugs through efflux pumps, which relies on the ATP-dependent expression and interaction of several controlling genes. Recent studies have shown that significant cell-to-cell ATP variability exists within clonal bacterial populations, but the contribution of intrinsic cell-to-cell ATP heterogeneity is generally overlooked in understanding efflux pumps. Here, we consider how ATP variability influences gene regulatory networks controlling expression of efflux pump genes in two bacterial species. We develop and apply a generalizable Boolean modelling framework, developed to incorporate the dependence of gene expression dynamics on available cellular energy supply. Theoretical results show that differences in energy availability can cause pronounced downstream heterogeneity in efflux gene expression. Cells with higher energy availability have a superior response to stressors. Furthermore, in the absence of stress, model bacteria develop heterogeneous pulses of efflux pump gene expression which contribute to a sustained sub-population of cells with increased efflux expression activity, potentially conferring a continuous pool of intrinsically resistant bacteria. This modelling approach thus reveals an important source of heterogeneity in cell responses to antimicrobials and sheds light on potentially targetable aspects of efflux pump-related antimicrobial resistance. | 2022 | 35078338 |
| 8283 | 1 | 0.9959 | Stress responses as determinants of antimicrobial resistance in Gram-negative bacteria. Bacteria encounter a myriad of potentially growth-compromising conditions in nature and in hosts of pathogenic bacteria. These 'stresses' typically elicit protective and/or adaptive responses that serve to enhance bacterial survivability. Because they impact upon many of the same cellular components and processes that are targeted by antimicrobials, adaptive stress responses can influence antimicrobial susceptibility. In targeting and interfering with key cellular processes, antimicrobials themselves are 'stressors' to which protective stress responses have also evolved. Cellular responses to nutrient limitation (nutrient stress), oxidative and nitrosative stress, cell envelope damage (envelope stress), antimicrobial exposure and other growth-compromising stresses, have all been linked to the development of antimicrobial resistance in Gram-negative bacteria - resulting from the stimulation of protective changes to cell physiology, activation of resistance mechanisms, promotion of resistant lifestyles (biofilms), and induction of resistance mutations. | 2012 | 22424589 |
| 9142 | 2 | 0.9958 | Mechanism of antibacterial phytoconstituents: an updated review. The increase of multiple drug resistance bacteria significantly diminishes the effectiveness of antibiotic armory and subsequently exaggerates the level of therapeutic failure. Phytoconstituents are exceptional substitutes for resistance-modifying vehicles. The plants appear to be a deep well for the discovery of novel antibacterial compounds. This is owing to the numerous enticing characteristics of plants, they are easily accessible and inexpensive, extracts or chemicals derived from plants typically have significant levels of action against infections, and they rarely cause serious adverse effects. The enormous selection of phytochemicals offers very distinct chemical structures that may provide both novel mechanisms of antimicrobial activity and deliver us with different targets in the interior of the bacterial cell. They can directly affect bacteria or act together with the crucial events of pathogenicity, in this manner decreasing the aptitude of bacteria to create resistance. Abundant phytoconstituents demonstrate various mechanisms of action toward multi drug resistance bacteria. Overall, this comprehensive review will provide insights into the potential of phytoconstituents as alternative treatments for bacterial infections, particularly those caused by multi drug resistance strains. By examining the current state of research in this area, the review will shed light on potential future directions for the development of new antimicrobial therapies. | 2024 | 38913205 |
| 8297 | 3 | 0.9958 | Novel RpoS-Dependent Mechanisms Strengthen the Envelope Permeability Barrier during Stationary Phase. Gram-negative bacteria have effective methods of excluding toxic compounds, including a largely impermeable outer membrane (OM) and a range of efflux pumps. Furthermore, when cells become nutrient limited, RpoS enacts a global expression change providing cross-protection against many stresses. Here, we utilized sensitivity to an anionic detergent (sodium dodecyl sulfate [SDS]) to probe changes occurring to the cell's permeability barrier during nutrient limitation. Escherichia coli is resistant to SDS whether cells are actively growing, carbon limited, or nitrogen limited. In actively growing cells, this resistance depends on the AcrAB-TolC efflux pump; however, this pump is not necessary for protection under either carbon-limiting or nitrogen-limiting conditions, suggesting an alternative mechanism(s) of SDS resistance. In carbon-limited cells, RpoS-dependent pathways lessen the permeability of the OM, preventing the necessity for efflux. In nitrogen-limited but not carbon-limited cells, the loss of rpoS can be completely compensated for by the AcrAB-TolC efflux pump. We suggest that this difference simply reflects the fact that nitrogen-limited cells have access to a metabolizable energy (carbon) source that can efficiently power the efflux pump. Using a transposon mutant pool sequencing (Tn-Seq) approach, we identified three genes, sanA, dacA, and yhdP, that are necessary for RpoS-dependent SDS resistance in carbon-limited stationary phase. Using genetic analysis, we determined that these genes are involved in two different envelope-strengthening pathways. These genes have not previously been implicated in stationary-phase stress responses. A third novel RpoS-dependent pathway appears to strengthen the cell's permeability barrier in nitrogen-limited cells. Thus, though cells remain phenotypically SDS resistant, SDS resistance mechanisms differ significantly between growth states. IMPORTANCE: Gram-negative bacteria are intrinsically resistant to detergents and many antibiotics due to synergistic activities of a strong outer membrane (OM) permeability barrier and efflux pumps that capture and expel toxic molecules eluding the barrier. When the bacteria are depleted of an essential nutrient, a program of gene expression providing cross-protection against many stresses is induced. Whether this program alters the OM to further strengthen the barrier is unknown. Here, we identify novel pathways dependent on the master regulator of stationary phase that further strengthen the OM permeability barrier during nutrient limitation, circumventing the need for efflux pumps. Decreased permeability of nutrient-limited cells to toxic compounds has important implications for designing new antibiotics capable of targeting Gram-negative bacteria that may be in a growth-limited state. | 2017 | 27821607 |
| 9144 | 4 | 0.9958 | Metal nanoparticles: understanding the mechanisms behind antibacterial activity. As the field of nanomedicine emerges, there is a lag in research surrounding the topic of nanoparticle (NP) toxicity, particularly concerned with mechanisms of action. The continuous emergence of bacterial resistance has challenged the research community to develop novel antibiotic agents. Metal NPs are among the most promising of these because show strong antibacterial activity. This review summarizes and discusses proposed mechanisms of antibacterial action of different metal NPs. These mechanisms of bacterial killing include the production of reactive oxygen species, cation release, biomolecule damages, ATP depletion, and membrane interaction. Finally, a comprehensive analysis of the effects of NPs on the regulation of genes and proteins (transcriptomic and proteomic) profiles is discussed. | 2017 | 28974225 |
| 8331 | 5 | 0.9957 | An activator regulates the DNA damage response and anti-phage defense networks in Moraxellaceae. DNA-damage chemicals, including many antibiotics, often induce prophage induction and phage outbreaks within microbial communities, posing a significant threat to bacterial survival. Moraxellaceae strains are clinically relevant due to their remarkable resistance to antibiotics and radiation. However, the cellular-level regulation mechanisms that underlie their DNA damage response and anti-phage defense remain extensively unexplored. Here, we report a WYL family protein, DdaA, that has replaced the ubiquitous SOS system during the evolution of Moraxellaceae. DdaA functions as an activator and directly regulates the transcriptional networks of both DNA damage response and anti-phage defense genes under conditions of DNA damage stress. Our findings elucidate a pathway that shows how these bacteria enhance their immunity under DNA damage and shed light on controlling the resistance of Moraxellaceae strains in clinical practice. | 2025 | 40874593 |
| 8159 | 6 | 0.9957 | Quaternary Ammonium Salts: Insights into Synthesis and New Directions in Antibacterial Applications. The overuse of antibiotics has led to the emergence of a large number of antibiotic-resistant genes in bacteria, and increasing evidence indicates that a fungicide with an antibacterial mechanism different from that of antibiotics is needed. Quaternary ammonium salts (QASs) are a biparental substance with good antibacterial properties that kills bacteria through simple electrostatic adsorption and insertion into cell membranes/altering of cell membrane permeability. Therefore, the probability of bacteria developing drug resistance is greatly reduced. In this review, we focus on the synthesis and application of single-chain QASs, double-chain QASs, heterocyclic QASs, and gemini QASs (GQASs). Some possible structure-function relationships of QASs are also summarized. As such, we hope this review will provide insight for researchers to explore more applications of QASs in the field of antimicrobials with the aim of developing systems for clinical applications. | 2023 | 36748912 |
| 8622 | 7 | 0.9957 | Antipsychotic quetiapine alters the mouse fecal resistome by impacting antibiotic efflux, cell membrane, and cell wall synthesis genes. This study significantly contributes to our understanding of how certain medications can unintentionally contribute to a major global health issue, i.e., antibiotic resistance. Quetiapine, a widely used antipsychotic medication, was found to increase key resistance mechanisms of gut bacteria to antibiotics in mice. Specifically, these data suggest that quetiapine may target elements of the bacterial cell membrane. If similar effects are found in humans, this medicine could unexpectedly make it harder to treat certain infections. This research emphasizes the importance of being mindful about not just antibiotics themselves, but also about other medications that could inadvertently contribute to this problem. Ultimately, these findings underline the necessity for more in-depth research on the broader impact of pharmaceuticals. | 2024 | 38099619 |
| 8282 | 8 | 0.9957 | Gut microbiota: a new player in regulating immune- and chemo-therapy efficacy. Development of drug resistance represents the major cause of cancer therapy failure, determines disease progression and results in poor prognosis for cancer patients. Different mechanisms are responsible for drug resistance. Intrinsic genetic modifications of cancer cells induce the alteration of expression of gene controlling specific pathways that regulate drug resistance: drug transport and metabolism; alteration of drug targets; DNA damage repair; and deregulation of apoptosis, autophagy, and pro-survival signaling. On the other hand, a complex signaling network among the entire cell component characterizes tumor microenvironment and regulates the pathways involved in the development of drug resistance. Gut microbiota represents a new player in the regulation of a patient's response to cancer therapies, including chemotherapy and immunotherapy. In particular, commensal bacteria can regulate the efficacy of immune checkpoint inhibitor therapy by modulating the activation of immune responses to cancer. Commensal bacteria can also regulate the efficacy of chemotherapeutic drugs, such as oxaliplatin, gemcitabine, and cyclophosphamide. Recently, it has been shown that such bacteria can produce extracellular vesicles (EVs) that can mediate intercellular communication with human host cells. Indeed, bacterial EVs carry RNA molecules with gene expression regulatory ability that can be delivered to recipient cells of the host and potentially regulate the expression of genes involved in controlling the resistance to cancer therapy. On the other hand, host cells can also deliver human EVs to commensal bacteria and similarly, regulate gene expression. EV-mediated intercellular communication between commensal bacteria and host cells may thus represent a novel research area into potential mechanisms regulating the efficacy of cancer therapy. | 2020 | 33062956 |
| 757 | 9 | 0.9956 | Regulation of antibiotic-resistance by non-coding RNAs in bacteria. Antibiotic resistance genes are commonly regulated by sophisticated mechanisms that activate gene expression in response to antibiotic exposure. Growing evidence suggest that cis-acting non-coding RNAs play a major role in regulating the expression of many resistance genes, specifically those which counteract the effects of translation-inhibiting antibiotics. These ncRNAs reside in the 5'UTR of the regulated gene, and sense the presence of the antibiotics by recruiting translating ribosomes onto short upstream open reading frames (uORFs) embedded in the ncRNA. In the presence of translation-inhibiting antibiotics ribosomes arrest over the uORF, altering the RNA structure of the regulator and switching the expression of the resistance gene to 'ON'. The specificity of these riboregulators is tuned to sense-specific classes of antibiotics based on the length and composition of the respective uORF. Here we review recent work describing new types of antibiotic-sensing RNA-based regulators and elucidating the molecular mechanisms by which they function to control antibiotic resistance in bacteria. | 2017 | 28414973 |
| 9141 | 10 | 0.9956 | Metallic Nanoparticles-Friends or Foes in the Battle against Antibiotic-Resistant Bacteria? The rapid spread of antibiotic resistances among bacteria demands novel strategies for infection control, and metallic nanoparticles appear as promising tools because of their unique size and tunable properties that allow their antibacterial effects to be maximized. Furthermore, their diverse mechanisms of action towards multiple cell components have suggested that bacteria could not easily develop resistance against nanoparticles. However, research published over the last decade has proven that bacteria can indeed evolve stable resistance mechanisms upon continuous exposure to metallic nanoparticles. In this review, we summarize the currently known individual and collective strategies employed by bacteria to cope with metallic nanoparticles. Importantly, we also discuss the adverse side effects that bacterial exposure to nanoparticles may have on antibiotic resistance dissemination and that might constitute a challenge for the implementation of nanoparticles as antibacterial agents. Overall, studies discussed in this review point out that careful management of these very promising antimicrobials is necessary to preserve their efficacy for infection control. | 2021 | 33673231 |
| 8290 | 11 | 0.9956 | Antimicrobial Peptides: Features, Action, and Their Resistance Mechanisms in Bacteria. In recent years, because of increased resistance to conventional antimicrobials, many researchers have started to study the synthesis of new antibiotics to control the disease-causing effects of infectious pathogens. Antimicrobial peptides (AMPs) are among the newest antibiotics; these peptides are integral compounds in all kinds of organisms and play a significant role in microbial ecology, and critically contribute to the innate immunity of organisms by destroying invading microorganisms. Moreover, AMPs may encourage cells to produce chemokines, stimulate angiogenesis, accelerate wound healing, and influence programmed cell death in multicellular organisms. Bacteria differ in their inherent susceptibility and resistance mechanisms to these peptides when responding to the antimicrobial effects of AMPs. Generally, the development of AMP resistance mechanisms is driven by direct competition between bacterial species, and host and pathogen interactions. Several studies have shown diverse mechanisms of bacterial resistance to AMPs, for example, some bacteria produce proteases and trapping proteins; some modify cell surface charge, change membrane fluidity, and activate efflux pumps; and some species make use of biofilms and exopolymers, and develop sensing systems by selective gene expression. A closer understanding of bacterial resistance mechanisms may help in developing novel therapeutic approaches for the treatment of infections caused by pathogenic organisms that are successful in developing extensive resistance to AMPs. Based on these observations, this review discusses the properties of AMPs, their targeting mechanisms, and bacterial resistance mechanisms against AMPs. | 2018 | 29957118 |
| 8339 | 12 | 0.9956 | Dynamical model of antibiotic responses linking expression of resistance genes to metabolism explains emergence of heterogeneity during drug exposures. Antibiotic responses in bacteria are highly dynamic and heterogeneous, with sudden exposure of bacterial colonies to high drug doses resulting in the coexistence of recovered and arrested cells. The dynamics of the response is determined by regulatory circuits controlling the expression of resistance genes, which are in turn modulated by the drug's action on cell growth and metabolism. Despite advances in understanding gene regulation at the molecular level, we still lack a framework to describe how feedback mechanisms resulting from the interdependence between expression of resistance and cell metabolism can amplify naturally occurring noise and create heterogeneity at the population level. To understand how this interplay affects cell survival upon exposure, we constructed a mathematical model of the dynamics of antibiotic responses that links metabolism and regulation of gene expression, based on the tetracycline resistancetetoperon inE. coli. We use this model to interpret measurements of growth and expression of resistance in microfluidic experiments, both in single cells and in biofilms. We also implemented a stochastic model of the drug response, to show that exposure to high drug levels results in large variations of recovery times and heterogeneity at the population level. We show that stochasticity is important to determine how nutrient quality affects cell survival during exposure to high drug concentrations. A quantitative description of how microbes respond to antibiotics in dynamical environments is crucial to understand population-level behaviors such as biofilms and pathogenesis. | 2024 | 38412523 |
| 9169 | 13 | 0.9955 | Interference of bacterial cell-to-cell communication: a new concept of antimicrobial chemotherapy breaks antibiotic resistance. Bacteria use a cell-to-cell communication activity termed "quorum sensing" to coordinate group behaviors in a cell density dependent manner. Quorum sensing influences the expression profile of diverse genes, including antibiotic tolerance and virulence determinants, via specific chemical compounds called "autoinducers". During quorum sensing, Gram-negative bacteria typically use an acylated homoserine lactone (AHL) called autoinducer 1. Since the first discovery of quorum sensing in a marine bacterium, it has been recognized that more than 100 species possess this mechanism of cell-to-cell communication. In addition to being of interest from a biological standpoint, quorum sensing is a potential target for antimicrobial chemotherapy. This unique concept of antimicrobial control relies on reducing the burden of virulence rather than killing the bacteria. It is believed that this approach will not only suppress the development of antibiotic resistance, but will also improve the treatment of refractory infections triggered by multi-drug resistant pathogens. In this paper, we review and track recent progress in studies on AHL inhibitors/modulators from a biological standpoint. It has been discovered that both natural and synthetic compounds can disrupt quorum sensing by a variety of means, such as jamming signal transduction, inhibition of signal production and break-down and trapping of signal compounds. We also focus on the regulatory elements that attenuate quorum sensing activities and discuss their unique properties. Understanding the biological roles of regulatory elements might be useful in developing inhibitor applications and understanding how quorum sensing is controlled. | 2013 | 23720655 |
| 8348 | 14 | 0.9955 | Role of RelA-synthesized (p)ppGpp and ROS-induced mutagenesis in de novo acquisition of antibiotic resistance in E. coli. The stringent response of bacteria to starvation and stress also fulfills a role in addressing the threat of antibiotics. Within this stringent response, (p)ppGpp, synthesized by RelA or SpoT, functions as a global alarmone. However, the effect of this (p)ppGpp on resistance development is poorly understood. Here, we show that knockout of relA or rpoS curtails resistance development against bactericidal antibiotics. The emergence of mutated genes associated with starvation and (p)ppGpp, among others, indicates the activation of stringent responses. The growth rate is decreased in ΔrelA-resistant strains due to the reduced ability to synthesize (p)ppGpp and the persistence of deacylated tRNA impeding protein synthesis. Sluggish cellular activity causes decreased production of reactive oxygen species (ROS), thereby reducing oxidative damage, leading to weakened DNA mismatch repair, potentially reducing the generation of mutations. These findings offer new targets for mitigating antibiotic resistance development, potentially achieved through inhibiting (p)ppGpp or ROS synthesis. | 2024 | 38617560 |
| 8341 | 15 | 0.9955 | Mutagenesis and Resistance Development of Bacteria Challenged by Silver Nanoparticles. Because of their extremely broad spectrum and strong biocidal power, nanoparticles of metals, especially silver (AgNPs), have been widely applied as effective antimicrobial agents against bacteria, fungi, and so on. However, the mutagenic effects of AgNPs and resistance mechanisms of target cells remain controversial. In this study, we discover that AgNPs do not speed up resistance mutation generation by accelerating genome-wide mutation rate of the target bacterium Escherichia coli. AgNPs-treated bacteria also show decreased expression in quorum sensing (QS), one of the major mechanisms leading to population-level drug resistance in microbes. Nonetheless, these nanomaterials are not immune to resistance development by bacteria. Gene expression analysis, experimental evolution in response to sublethal or bactericidal AgNPs treatments, and gene editing reveal that bacteria acquire resistance mainly through two-component regulatory systems, especially those involved in metal detoxification, osmoregulation, and energy metabolism. Although these findings imply low mutagenic risks of nanomaterial-based antimicrobial agents, they also highlight the capacity for bacteria to evolve resistance. | 2022 | 36094196 |
| 779 | 16 | 0.9955 | The menaquinone pathway is important for susceptibility of Staphylococcus aureus to the antibiotic adjuvant, cannabidiol. Emergence of antibiotic resistant bacteria is evolving at an alarming pace; therefore, we must start turning to alternative approaches. One of these, could be the use of antibiotic adjuvants that enhances the effect of antibiotics towards resistant bacteria. A novel antibiotic adjuvant is cannabidiol (CBD), which we have previously shown can enhance the effect of bacitracin (BAC). BAC targets cell wall synthesis by inhibiting dephosphorylation of the lipid carrier undecaprenyl pyrophosphate prior to recycling across the membrane. However, the mechanism underlying this CBD mediated potentiation of BAC has remained unknown. To explore this, we examined resistance to CBD in Staphylococcus aureus through daily exposures to CBD. By subsequent whole genome sequencing, we observed multiple genes to be mutated, including the farE/farR system encoding a fatty acid efflux pump (FarE) and its regulator (FarR). Importantly, recreation of mutations in these genes showed decreased susceptibility towards the combination of CBD and BAC. Furthermore, we searched the Nebraska Transposon Mutant Library for CBD susceptible strains and identified menH encoding a protein participating in menaquinone biosynthesis. Strains containing deletions in this and other menaquinone related genes showed increased susceptibility towards CBD, while addition of exogenous menaquinone reversed the effect and reduced susceptible towards CBD. These results suggest that CBD potentiates BAC by redirecting the isoprenoid precursor isopentenyl pyrophosphate towards production of menaquinone rather than the lipid carrier undecaprenyl pyrophosphate, which dephosphorylation is inhibited by BAC. This in turn might decrease the level of undecaprenyl pyrophosphate thus enhancing the effect of BAC. Our study illustrates how antibiotic adjuvants may apply to enhance efficacy of antimicrobial compounds. | 2022 | 35091344 |
| 8347 | 17 | 0.9955 | Molecular mechanisms underlying glyphosate resistance in bacteria. Glyphosate is a nonselective herbicide that kills weeds and other plants competing with crops. Glyphosate specifically inhibits the 5-enolpyruvyl-shikimate-3-phosphate (EPSP) synthase, thereby depleting the cell of EPSP serving as a precursor for biosynthesis of aromatic amino acids. Glyphosate is considered to be toxicologically safe for animals and humans. Therefore, it became the most-important herbicide in agriculture. However, its intensive application in agriculture is a serious environmental issue because it may negatively affect the biodiversity. A few years after the discovery of the mode of action of glyphosate, it has been observed that bacteria evolve glyphosate resistance by acquiring mutations in the EPSP synthase gene, rendering the encoded enzyme less sensitive to the herbicide. The identification of glyphosate-resistant EPSP synthase variants paved the way for engineering crops tolerating increased amounts of the herbicide. This review intends to summarize the molecular mechanisms underlying glyphosate resistance in bacteria. Bacteria can evolve glyphosate resistance by (i) reducing glyphosate sensitivity or elevating production of the EPSP synthase, by (ii) degrading or (iii) detoxifying glyphosate and by (iv) decreasing the uptake or increasing the export of the herbicide. The variety of glyphosate resistance mechanisms illustrates the adaptability of bacteria to anthropogenic substances due to genomic alterations. | 2021 | 33876549 |
| 8285 | 18 | 0.9954 | Bacterial stress response: understanding the molecular mechanics to identify possible therapeutic targets. INTRODUCTION: Bacteria are ubiquitous and many of them are pathogenic in nature. Entry of bacteria in host and its recognition by host defense system induce stress in host cells. With time, bacteria have also developed strategies including drug resistance to escape from antibacterial therapy as well as host defense mechanism. AREAS COVERED: Bacterial stress initiates and promotes adaptive immune response through several integrated mechanisms. The mechanisms of bacteria to up and down regulate different pathways involved in these responses have been discussed. The genetic expression of these pathways can be manipulated by the pharmacological interventions. Present review discusses in these contexts and explores the possibilities to overcome stress induced by bacterial pathogens and to suggest new possible therapeutic targets. EXPERT OPINION: In our opinion, there are two important fronts to regulate the bacterial stress. One is to target caspase involved in the process of transformation and translation at gene level and protein expression. Second is the identification of bacterial genes that lead to synthesis of abnormal end products supporting bacterial survival in host environment and also to surpass the host defense mechanism. Identification of such genes and their expression products could be an effective option to encounter bacterial resistance. | 2021 | 32811215 |
| 9175 | 19 | 0.9954 | Fitness Trade-Offs Resulting from Bacteriophage Resistance Potentiate Synergistic Antibacterial Strategies. Bacteria that cause life-threatening infections in humans are becoming increasingly difficult to treat. In some instances, this is due to intrinsic and acquired antibiotic resistance, indicating that new therapeutic approaches are needed to combat bacterial pathogens. There is renewed interest in utilizing viruses of bacteria known as bacteriophages (phages) as potential antibacterial therapeutics. However, critics suggest that similar to antibiotics, the development of phage-resistant bacteria will halt clinical phage therapy. Although the emergence of phage-resistant bacteria is likely inevitable, there is a growing body of literature showing that phage selective pressure promotes mutations in bacteria that allow them to subvert phage infection, but with a cost to their fitness. Such fitness trade-offs include reduced virulence, resensitization to antibiotics, and colonization defects. Resistance to phage nucleic acid entry, primarily via cell surface modifications, compromises bacterial fitness during antibiotic and host immune system pressure. In this minireview, we explore the mechanisms behind phage resistance in bacterial pathogens and the physiological consequences of acquiring phage resistance phenotypes. With this knowledge, it may be possible to use phages to alter bacterial populations, making them more tractable to current therapeutic strategies. | 2020 | 32094257 |