# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9222 | 0 | 0.9948 | Bacterial proton motive force as an unprecedented target to control antimicrobial resistance. Novel antibacterial therapies are urgently required to tackle the increasing number of multidrug-resistant pathogens. Identification of new antimicrobial targets is critical to avoid possible cross-resistance issues. Bacterial proton motive force (PMF), an energetic pathway located on the bacterial membrane, crucially regulates various biological possesses such as adenosine triphosphate synthesis, active transport of molecules, and rotation of bacterial flagella. Nevertheless, the potential of bacterial PMF as an antibacterial target remains largely unexplored. The PMF generally comprises electric potential (ΔΨ) and transmembrane proton gradient (ΔpH). In this review, we present an overview of bacterial PMF, including its functions and characterizations, highlighting the representative antimicrobial agents that specifically target either ΔΨ or ΔpH. At the same time, we also discuss the adjuvant potential of bacterial PMF-targeting compounds. Lastly, we highlight the value of PMF disruptors in preventing the transmission of antibiotic resistance genes. These findings suggest that bacterial PMF represents an unprecedented target, providing a comprehensive approach to controlling antimicrobial resistance. | 2023 | 36896761 |
| 8283 | 1 | 0.9948 | 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 |
| 8329 | 2 | 0.9947 | Protozoan predation enhances stress resistance and antibiotic tolerance in Burkholderia cenocepacia by triggering the SOS response. Bacterivorous protists are thought to serve as training grounds for bacterial pathogens by subjecting them to the same hostile conditions that they will encounter in the human host. Bacteria that survive intracellular digestion exhibit enhanced virulence and stress resistance after successful passage through protozoa but the underlying mechanisms are unknown. Here we show that the opportunistic pathogen Burkholderia cenocepacia survives phagocytosis by ciliates found in domestic and hospital sink drains, and viable bacteria are expelled packaged in respirable membrane vesicles with enhanced resistance to oxidative stress, desiccation, and antibiotics, thereby contributing to pathogen dissemination in the environment. Reactive oxygen species generated within the protozoan phagosome promote the formation of persisters tolerant to ciprofloxacin by activating the bacterial SOS response. In addition, we show that genes encoding antioxidant enzymes are upregulated during passage through ciliates increasing bacterial resistance to oxidative radicals. We prove that suppression of the SOS response impairs bacterial intracellular survival and persister formation within protists. This study highlights the significance of protozoan food vacuoles as niches that foster bacterial adaptation in natural and built environments and suggests that persister switch within phagosomes may be a widespread phenomenon in bacteria surviving intracellular digestion. | 2024 | 38366016 |
| 8331 | 3 | 0.9947 | 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 |
| 583 | 4 | 0.9947 | MarR family proteins sense sulfane sulfur in bacteria. Members of the multiple antibiotic resistance regulator (MarR) protein family are ubiquitous in bacteria and play critical roles in regulating cellular metabolism and antibiotic resistance. MarR family proteins function as repressors, and their interactions with modulators induce the expression of controlled genes. The previously characterized modulators are insufficient to explain the activities of certain MarR family proteins. However, recently, several MarR family proteins have been reported to sense sulfane sulfur, including zero-valent sulfur, persulfide (R-SSH), and polysulfide (R-SnH, n ≥ 2). Sulfane sulfur is a common cellular component in bacteria whose levels vary during bacterial growth. The changing levels of sulfane sulfur affect the expression of many MarR-controlled genes. Sulfane sulfur reacts with the cysteine thiols of MarR family proteins, causing the formation of protein thiol persulfide, disulfide bonds, and other modifications. Several MarR family proteins that respond to reactive oxygen species (ROS) also sense sulfane sulfur, as both sulfane sulfur and ROS induce the formation of disulfide bonds. This review focused on MarR family proteins that sense sulfane sulfur. However, the sensing mechanisms reviewed here may also apply to other proteins that detect sulfane sulfur, which is emerging as a modulator of gene regulation. | 2024 | 38948149 |
| 8601 | 5 | 0.9947 | Herbicide promotes the conjugative transfer of multi-resistance genes by facilitating cellular contact and plasmid transfer. The global dissemination of antibiotic resistance genes (ARGs), especially via plasmid-mediated horizontal transfer, is becoming a pervasive health threat. While our previous study found that herbicides can accelerate the horizontal gene transfer (HGT) of ARGs in soil bacteria, the underlying mechanisms by which herbicides promote the HGT of ARGs across and within bacterial genera are still unclear. Here, the underlying mechanism associated with herbicide-promoted HGT was analyzed by detecting intracellular reactive oxygen species (ROS) production, extracellular polymeric substance composition, cell membrane integrity and proton motive force combined with genome-wide RNA sequencing. Exposure to herbicides induced a series of the above bacterial responses to promote HGT except for the ROS response, including compact cell-to-cell contact by enhancing pilus-encoded gene expression and decreasing cell surface charge, increasing cell membrane permeability, and enhancing the proton motive force, providing additional power for DNA uptake. This study provides a mechanistic understanding of the risk of bacterial resistance spread promoted by herbicides, which elucidates a new perspective on nonantibiotic agrochemical acceleration of the HGT of ARGs. | 2022 | 34969463 |
| 9144 | 6 | 0.9946 | 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 |
| 8144 | 7 | 0.9946 | Fungal Priming: Prepare or Perish. Priming (also referred to as acclimation, acquired stress resistance, adaptive response, or cross-protection) is defined as an exposure of an organism to mild stress that leads to the development of a subsequent stronger and more protective response. This memory of a previously encountered stress likely provides a strong survival advantage in a rapidly shifting environment. Priming has been identified in animals, plants, fungi, and bacteria. Examples include innate immune priming and transgenerational epigenetic inheritance in animals and biotic and abiotic stress priming in plants, fungi, and bacteria. Priming mechanisms are diverse and include alterations in the levels of specific mRNAs, proteins, metabolites, and epigenetic changes such as DNA methylation and histone acetylation of target genes. | 2022 | 35628704 |
| 728 | 8 | 0.9945 | Surviving Reactive Chlorine Stress: Responses of Gram-Negative Bacteria to Hypochlorous Acid. Sodium hypochlorite (NaOCl) and its active ingredient, hypochlorous acid (HOCl), are the most commonly used chlorine-based disinfectants. HOCl is a fast-acting and potent antimicrobial agent that interacts with several biomolecules, such as sulfur-containing amino acids, lipids, nucleic acids, and membrane components, causing severe cellular damage. It is also produced by the immune system as a first-line of defense against invading pathogens. In this review, we summarize the adaptive responses of Gram-negative bacteria to HOCl-induced stress and highlight the role of chaperone holdases (Hsp33, RidA, Cnox, and polyP) as an immediate response to HOCl stress. We also describe the three identified transcriptional regulators (HypT, RclR, and NemR) that specifically respond to HOCl. Besides the activation of chaperones and transcriptional regulators, the formation of biofilms has been described as an important adaptive response to several stressors, including HOCl. Although the knowledge on the molecular mechanisms involved in HOCl biofilm stimulation is limited, studies have shown that HOCl induces the formation of biofilms by causing conformational changes in membrane properties, overproducing the extracellular polymeric substance (EPS) matrix, and increasing the intracellular concentration of cyclic-di-GMP. In addition, acquisition and expression of antibiotic resistance genes, secretion of virulence factors and induction of the viable but nonculturable (VBNC) state has also been described as an adaptive response to HOCl. In general, the knowledge of how bacteria respond to HOCl stress has increased over time; however, the molecular mechanisms involved in this stress response is still in its infancy. A better understanding of these mechanisms could help understand host-pathogen interactions and target specific genes and molecules to control bacterial spread and colonization. | 2020 | 32796669 |
| 726 | 9 | 0.9945 | Regulation of antimicrobial resistance by extracytoplasmic function (ECF) sigma factors. Extracytoplasmic function (ECF) sigma factors are a subfamily of σ(70) sigma factors that activate genes involved in stress-response functions. In many bacteria, ECF sigma factors regulate resistance to antimicrobial compounds. This review will summarize the ECF sigma factors that regulate antimicrobial resistance in model organisms and clinically relevant pathogens. | 2017 | 28153747 |
| 8282 | 10 | 0.9945 | 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 |
| 8599 | 11 | 0.9945 | Artificial sweeteners stimulate horizontal transfer of extracellular antibiotic resistance genes through natural transformation. Antimicrobial resistance has emerged as a global threat to human health. Natural transformation is an important pathway for horizontal gene transfer, which facilitates the dissemination of antibiotic resistance genes (ARGs) among bacteria. Although it is suspected that artificial sweeteners could exert antimicrobial effects, little is known whether artificial sweeteners would also affect horizontal transfer of ARGs via transformation. Here we demonstrate that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) promote transfer of ARGs via natural transformation in Acinetobacter baylyi ADP1, a model organism for studying competence and transformation. Such phenomenon was also found in a Gram-positive human pathogen Bacillus subtilis and mice faecal microbiome. We reveal that exposure to these sweeteners increases cell envelope permeability and results in an upregulation of genes encoding DNA uptake and translocation (Com) machinery. In addition, we find that artificial sweeteners induce an increase in plasmid persistence in transformants. We propose a mathematical model established to predict the long-term effects on transformation dynamics under exposure to these sweeteners. Collectively, our findings offer insights into natural transformation promoted by artificial sweeteners and highlight the need to evaluate these environmental contaminants for their antibiotic-like side effects. | 2022 | 34465899 |
| 9173 | 12 | 0.9945 | Bacterial 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. | 2023 | 37095190 |
| 8137 | 13 | 0.9944 | Modulation 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. | 2020 | 33747974 |
| 8616 | 14 | 0.9944 | Mechanisms of inhibition and recovery under multi-antibiotic stress in anammox: A critical review. With the escalating global concern for emerging pollutants, particularly antibiotics, microplastics, and nanomaterials, the potential disruption they pose to critical environmental processes like anaerobic ammonia oxidation (anammox) has become a pressing issue. The anammox process, which plays a crucial role in nitrogen removal from wastewater, is particularly sensitive to external pollutants. This paper endeavors to address this knowledge gap by providing a comprehensive overview of the inhibition mechanisms of multi-antibiotic on anaerobic ammonia-oxidizing bacteria, along with insights into their recovery processes. The paper dives deeply into the various ways antibiotics interact with anammox bacteria, focusing specifically on their interference with the bacteria's extracellular polymers (EPS) - crucial components that maintain the structural integrity and functionality of the cells. Additionally, it explores how anammox bacteria utilize quorum sensing (QS) mechanisms to regulate their community structure and respond to antibiotic stress. Moreover, the paper summarizes effective removal methods for these antibiotics from wastewater systems, which is crucial for mitigating their inhibitory effects on anammox bacteria. Finally, the paper offers valuable insights into how anammox communities can recuperate from multi-antibiotic stress. This includes strategies for reintroducing healthy bacteria, optimizing operational conditions, and using bioaugmentation techniques to enhance the resilience of anammox communities. In summary, this paper not only enriches our understanding of the complex interactions between antibiotics and anammox bacteria but also provides theoretical and practical guidance for the treatment of antibiotic pollution in sewage, ensuring the sustainability and effectiveness of wastewater treatment processes. | 2024 | 39366232 |
| 9371 | 15 | 0.9944 | Coevolutionary history of predation constrains the evolvability of antibiotic resistance in prey bacteria. Understanding how the historical contingency of biotic interactions shapes the evolvability of bacterial populations is imperative for the predictability of the eco-evolutionary dynamics of microbial communities. While microbial predators like Myxococcus xanthus influence the frequency of antibiotic-resistant bacteria in nature, the effect of adaptation to the presence of predators on the evolvability of prey bacteria to future stressors is unclear. Hence, to understand the influence of the coevolutionary history of predation on the evolvability of antibiotic resistance, we propagated variants of E. coli, pre-adapted to distinct biotic and abiotic conditions, in gradually increasing concentrations of antibiotics. We show that pre-adaptation to predators limits the evolution of a high degree of antibiotic resistance. Moreover, lower degree of resistance in the evolved strains also incurs reduced fitness costs while preserving their ancestral ability to resist predation. Together, we demonstrate that the history of biotic interactions can strongly influence the evolvability of bacteria. | 2025 | 40461734 |
| 757 | 16 | 0.9944 | 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 |
| 8635 | 17 | 0.9944 | Techniques for enhancing the tolerance of industrial microbes to abiotic stresses: A review. The diversity of stress responses and survival strategies evolved by microorganism enables them to survive and reproduce in a multitude of harsh environments, whereas the discovery of the underlying resistance genes or mechanisms laid the foundation for the directional enhancement of microbial tolerance to abiotic stresses encountered in industrial applications. Many biological techniques have been developed for improving the stress resistance of industrial microorganisms, which greatly benefited the bacteria on which industrial production is based. This review introduces the main techniques for enhancing the resistance of microorganisms to abiotic stresses, including evolutionary engineering, metabolic engineering, and process engineering, developed in recent years. In addition, we also discuss problems that are still present in this area and offer directions for future research. | 2020 | 31206805 |
| 727 | 18 | 0.9944 | Bacillus subtilis extracytoplasmic function (ECF) sigma factors and defense of the cell envelope. Bacillus subtilis provides a model for investigation of the bacterial cell envelope, the first line of defense against environmental threats. Extracytoplasmic function (ECF) sigma factors activate genes that confer resistance to agents that threaten the integrity of the envelope. Although their individual regulons overlap, σ(W) is most closely associated with membrane-active agents, σ(X) with cationic antimicrobial peptide resistance, and σ(V) with resistance to lysozyme. Here, I highlight the role of the σ(M) regulon, which is strongly induced by conditions that impair peptidoglycan synthesis and includes the core pathways of envelope synthesis and cell division, as well as stress-inducible alternative enzymes. Studies of these cell envelope stress responses provide insights into how bacteria acclimate to the presence of antibiotics. | 2016 | 26901131 |
| 8330 | 19 | 0.9944 | Increased iron utilization and oxidative stress tolerance in a Vibrio cholerae flrA mutant confers resistance to amoeba predation. Persistence of V. cholerae in the aquatic environment contributes to the fatal diarrheal disease cholera, which remains a global health burden. In the environment, bacteria face predation pressure by heterotrophic protists such as the free-living amoeba A. castellanii. This study explores how a mutant of V. cholerae adapts to acquire essential nutrients and survive predation. Here, we observed that up-regulation of iron acquisition genes and genes regulating resistance to oxidative stress enhances pathogen fitness. Our data show that V. cholerae can defend predation to overcome nutrient limitation and oxidative stress, resulting in an enhanced survival inside the protozoan hosts. | 2023 | 37882527 |