Bacterial Stress Responses as Potential Targets in Overcoming Antibiotic Resistance. - Related Documents




#
Rank
Similarity
Title + Abs.
Year
PMID
012345
834301.0000Bacterial Stress Responses as Potential Targets in Overcoming Antibiotic Resistance. Bacteria can be adapted to adverse and detrimental conditions that induce general and specific responses to DNA damage as well as acid, heat, cold, starvation, oxidative, envelope, and osmotic stresses. The stress-triggered regulatory systems are involved in bacterial survival processes, such as adaptation, physiological changes, virulence potential, and antibiotic resistance. Antibiotic susceptibility to several antibiotics is reduced due to the activation of stress responses in cellular physiology by the stimulation of resistance mechanisms, the promotion of a resistant lifestyle (biofilm or persistence), and/or the induction of resistance mutations. Hence, the activation of bacterial stress responses poses a serious threat to the efficacy and clinical success of antibiotic therapy. Bacterial stress responses can be potential targets for therapeutic alternatives to antibiotics. An understanding of the regulation of stress response in association with antibiotic resistance provides useful information for the discovery of novel antimicrobial adjuvants and the development of effective therapeutic strategies to control antibiotic resistance in bacteria. Therefore, this review discusses bacterial stress responses linked to antibiotic resistance in Gram-negative bacteria and also provides information on novel therapies targeting bacterial stress responses that have been identified as potential candidates for the effective control of Gram-negative antibiotic-resistant bacteria.202235889104
834210.9999Inflammatory immunity and bacteriological perspectives: A new direction for copper treatment of sepsis. Copper is an essential trace element for all aerobic organisms because of its unique biological functions. In recent years, researchers have discovered that copper can induce cell death through various regulatory mechanisms, thereby inducing inflammation. Efforts have also been made to alter the chemical structure of copper to achieve either anticancer or anti-inflammatory effects. The copper ion can exhibit bactericidal effects by interfering with the integrity of the cell membrane and promoting oxidative stress. Sepsis is a systemic inflammatory response caused by infection. Some studies have revealed that copper is involved in the pathophysiological process of sepsis and is closely related to its prognosis. During the infection of sepsis, the body may enhance the antimicrobial effect by increasing the release of copper. However, to avoid copper poisoning, all organisms have evolved copper resistance genes. Therefore, further analysis of the complex relationship between copper and bacteria may provide new ideas and research directions for the treatment of sepsis.202438692229
834120.9999Mutagenesis 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.202236094196
915230.9999Pseudomonas aeruginosa biofilm sensitivity to biocides: use of hydrogen peroxide as model antimicrobial agent for examining resistance mechanisms. The biofilm mode of bacterial growth may be the preferred form of existence in nature. Because of the global impact of problematic biofilms, study of the mechanisms affording resistance to various biocides is of dire importance. Furthermore, understanding the physiological differences between biofilm and planktonic organisms ranks particularly high on the list of important and necessary research. Such contributions will only serve to broaden our knowledge base, especially regarding the development of better antimicrobials while also fine-tuning the use of current highly effective antimicrobials. Using H2O2 as a model oxidizing biocide, we demonstrate the marked resistance of biofilm bacteria relative to planktonic cells. Because many biocides are good oxidizing agents (e.g., H2O2, HOCl), understanding the mechanisms by which genes involved in combating oxidative stress are activated is important in determining the overall efficacy of such biocides. Future studies will focus on determining mechanisms of oxidative stress gene regulation in bacterial biofilms.199910547822
828540.9999Bacterial 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.202132811215
828450.9999Redox signaling in human pathogens. In recent studies of human bacterial pathogens, oxidation sensing and regulation have been shown to impact very diverse pathways that extend beyond inducing antioxidant genes in the bacteria. In fact, some redox-sensitive regulatory proteins act as major regulators of bacteria's adaptability to oxidative stress, an ability that originates from immune host response as well as antibiotic stress. Such proteins play particularly important roles in pathogenic bacteria S. aureus, P. aeruginosa, and M. tuberculosis in part because reactive oxygen species and reactive nitrogen species present significant challenges for pathogens during infection. Herein, we review recent progress toward the identification and understanding of oxidation sensing and regulation in human pathogens. The newly identified redox switches in pathogens are a focus of this review. We will cover several reactive oxygen species-sensing global regulators in both gram-positive and gram-negative pathogenic bacteria in detail. The following discussion of the mechanisms that these proteins employ to sense redox signals through covalent modification of redox active amino acid residues or associated metalloprotein centers will provide further understanding of bacteria pathogenesis, antibiotic resistance, and host-pathogen interaction.201120578795
834060.9999Iron-Induced Respiration Promotes Antibiotic Resistance in Actinomycete Bacteria. The bacterial response to antibiotics eliciting resistance is one of the key challenges in global health. Despite many attempts to understand intrinsic antibiotic resistance, many of the underlying mechanisms still remain elusive. In this study, we found that iron supplementation promoted antibiotic resistance in Streptomyces coelicolor. Iron-promoted resistance occurred specifically against bactericidal antibiotics, irrespective of the primary target of antibiotics. Transcriptome profiling revealed that some genes in the central metabolism and respiration were upregulated under iron-replete conditions. Iron supported the growth of S. coelicolor even under anaerobic conditions. In the presence of potassium cyanide, which reduces aerobic respiration of cells, iron still promoted respiration and antibiotic resistance. This suggests the involvement of a KCN-insensitive type of respiration in the iron effect. This phenomenon was also observed in another actinobacterium, Mycobacterium smegmatis. Taken together, these findings provide insight into a bacterial resistance strategy that mitigates the activity of bactericidal antibiotics whose efficacy accompanies oxidative damage by switching the respiration mode. IMPORTANCE A widely investigated mode of antibiotic resistance occurs via mutations and/or by horizontal acquisition of resistance genes. In addition to this acquired resistance, most bacteria exhibit intrinsic resistance as an inducible and adaptive response to different classes of antibiotics. Increasing attention has been paid recently to intrinsic resistance mechanisms because this may provide novel therapeutic targets that help rejuvenate the efficacy of the current antibiotic regimen. In this study, we demonstrate that iron promotes the intrinsic resistance of aerobic actinomycetes Streptomyces coelicolor and Mycobacterium smegmatis against bactericidal antibiotics. A surprising role of iron to increase respiration, especially in a mode of using less oxygen, appears a fitting strategy to cope with bactericidal antibiotics known to kill bacteria through oxidative damage. This provides new insights into developing antimicrobial treatments based on the availability of iron and oxygen.202235357210
828670.9999RNA Modifications in Pathogenic Bacteria: Impact on Host Adaptation and Virulence. RNA modifications are involved in numerous biological processes and are present in all RNA classes. These modifications can be constitutive or modulated in response to adaptive processes. RNA modifications play multiple functions since they can impact RNA base-pairings, recognition by proteins, decoding, as well as RNA structure and stability. However, their roles in stress, environmental adaptation and during infections caused by pathogenic bacteria have just started to be appreciated. With the development of modern technologies in mass spectrometry and deep sequencing, recent examples of modifications regulating host-pathogen interactions have been demonstrated. They show how RNA modifications can regulate immune responses, antibiotic resistance, expression of virulence genes, and bacterial persistence. Here, we illustrate some of these findings, and highlight the strategies used to characterize RNA modifications, and their potential for new therapeutic applications.202134440299
833880.9999SOS, the formidable strategy of bacteria against aggressions. The presence of an abnormal amount of single-stranded DNA in the bacterial cell constitutes a genotoxic alarm signal that induces the SOS response, a broad regulatory network found in most bacterial species to address DNA damage. The aim of this review was to point out that beyond being a repair process, SOS induction leads to a very strong but transient response to genotoxic stress, during which bacteria can rearrange and mutate their genome, induce several phenotypic changes through differential regulation of genes, and sometimes acquire characteristics that potentiate bacterial survival and adaptation to changing environments. We review here the causes and consequences of SOS induction, but also how this response can be modulated under various circumstances and how it is connected to the network of other important stress responses. In the first section, we review articles describing the induction of the SOS response at the molecular level. The second section discusses consequences of this induction in terms of DNA repair, changes in the genome and gene expression, and sharing of genomic information, with their effects on the bacteria's life and evolution. The third section is about the fine tuning of this response to fit with the bacteria's 'needs'. Finally, we discuss recent findings linking the SOS response to other stress responses. Under these perspectives, SOS can be perceived as a powerful bacterial strategy against aggressions.201424923554
915190.9998Bacterial exo-polysaccharides in biofilms: role in antimicrobial resistance and treatments. BACKGROUND: Bacterial biofilms are aggregation or collection of different bacterial cells which are covered by self-produced extracellular matrix and are attached to a substratum. Generally, under stress or in unfavorable conditions, free planktonic bacteria transform themselves into bacterial biofilms and become sessile. MAIN BODY: Various mechanisms involving interaction between antimicrobial and biofilm matrix components, reduced growth rates, and genes conferring antibiotic resistance have been described to contribute to enhanced resistance. Quorum sensing and multi-drug resistance efflux pumps are known to regulate the internal environment within the biofilm as well as biofilm formation; they also protect cells from antibiotic attack or immune attacks. This review summarizes data supporting the importance of exopolysaccharides during biofilm formation and its role in antibiotic resistance. CONCLUSIONS: Involvement of quorum sensing and efflux pumps in antibiotic resistance in association with exopolysaccharides. Also, strategies to overcome or attack biofilms are provided.202134557983
9146100.9998Emergence of microbial resistance against nanoparticles: Mechanisms and strategies. Antimicrobial nanoparticles have gained the status of a new generation of drugs that can kill bacterial pathogens by multiple means; however, nanoparticle resistance acquired by some bacterial pathogens has evoked a cause of concern. Several reports suggested that bacteria can develop nanoparticles, specifically metal nanoparticle resistance, by mechanisms: nanoparticle transformation-induced oxidative stress, membrane alterations, reversible adaptive resistance, irreversible modifications to cell division, and a change in bacterial motility and resistance. Surface properties, concentration and aggregation of nanoparticles, biofilm forming and metal exclusion capacity, and R plasmid and flagellin synthesis by bacteria are crucial factors in the development of nanoparticle resistance in bacteria. Studies reported the resistance reversal by modifying the surface corona of nanoparticles or inhibiting flagellin production by bacterial pathogens. Furthermore, strict regulation regarding the use and disposal of nano-waste across the globe, the firm knowledge of microbe-nanoparticle interaction, and the regulated disposal of nanoparticles in soil and water is required to prevent microbes from developing nanoparticle resistance.202336778867
9427110.9998Polysaccharides' Structures and Functions in Biofilm Architecture of Antimicrobial-Resistant (AMR) Pathogens. Bacteria and fungi have developed resistance to the existing therapies such as antibiotics and antifungal drugs, and multiple mechanisms are mediating this resistance. Among these, the formation of an extracellular matrix embedding different bacterial cells, called biofilm, is an effective strategy through which bacterial and fungal cells are establishing a relationship in a unique environment. The biofilm provides them the possibility to transfer genes conferring resistance, to prevent them from desiccation and to impede the penetration of antibiotics or antifungal drugs. Biofilms are formed of several constituents including extracellular DNA, proteins and polysaccharides. Depending on the bacteria, different polysaccharides form the biofilm matrix in different microorganisms, some of them involved in the first stage of cells' attachment to surfaces and to each other, and some responsible for giving the biofilm structure resistance and stability. In this review, we describe the structure and the role of different polysaccharides in bacterial and fungal biofilms, we revise the analytical methods to characterize them quantitatively and qualitatively and finally we provide an overview of potential new antimicrobial therapies able to inhibit biofilm formation by targeting exopolysaccharides.202336835442
8283120.9998Stress 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.201222424589
8242130.9998New antibacterial targets: Regulation of quorum sensing and secretory systems in zoonotic bacteria. Quorum sensing (QS) is a communication mechanism that controls bacterial communication and can influence the transcriptional expression of multiple genes through one or more signaling molecules, thereby coordinating the population response of multiple bacterial pathogens. Secretion systems (SS) play an equally important role in bacterial information exchange, relying on the secretory systems to secrete proteins that act as virulence factors to promote adhesion to host cells. Eight highly efficient SS have been described, all of which are involved in the secretion or transfer of virulence factors, and the effector proteins they secrete play a key role in the virulence and pathogenicity of bacteria. It has been shown that many bacterial SS are directly or indirectly regulated by QS and thus influence bacterial virulence and antibiotic resistance. This review describes the relationship between QS and SS of several common zoonotic pathogenic bacteria and outlines the molecular mechanisms of how QS systems regulate SS, to provide a theoretical basis for the study of bacterial pathogenicity and the development of novel antibacterial drugs.202337343493
9541140.9998The Role of the Hfq Protein in Bacterial Resistance to Antibiotics: A Narrative Review. The antibiotic resistance of pathogenic microorganisms is currently one of most major medical problems, causing a few million deaths every year worldwide due to untreatable bacterial infections. Unfortunately, the prognosis is even worse, as over 8 million deaths associated with antibiotic resistance are expected to occur in 2050 if no new effective antibacterial treatments are discovered. The Hfq protein has been discovered as a bacterial RNA chaperone. However, subsequent studies have indicated that this small protein (composed of 102 amino acid residues in Escherichia coli) has more activities, including binding to DNA and influencing its compaction, interaction with biological membranes, formation of amyloid-like structures, and others. Although Hfq is known to participate in many cellular processes, perhaps surprisingly, only reports from recent years have demonstrated its role in bacterial antibiotic resistance. The aim of this narrative review is to discuss how can Hfq affects antibiotic resistance in bacteria and propose how this knowledge may facilitate developing new therapeutic strategies against pathogenic bacteria. We indicate that the mechanisms by which the Hfq protein modulates the response of bacterial cells to antibiotics are quite different, from the regulation of the expression of genes coding for proteins directly involved in antibiotic transportation or action, through direct effects on membranes, to controlling the replication or transposition of mobile genetic elements bearing antibiotic resistance genes. Therefore, we suggest that Hfq could be considered a potential target for novel antimicrobial compounds. We also discuss difficulties in developing such drugs, but since Hfq appears to be a promising target for drugs that may enhance the efficacy of antibiotics, we propose that works on such potential therapeutics are encouraged.202540005731
8311150.9998Perturbation of Quorum Sensing after the Acquisition of Bacteriophage Resistance Could Contribute to Novel Traits in Vibrio alginolyticus. Bacteria employ a wide range of molecular mechanisms to confer resistance to bacteriophages, and these mechanisms are continuously being discovered and characterized. However, there are instances where certain bacterial species, despite lacking these known mechanisms, can still develop bacteriophage resistance through intricate metabolic adaptation strategies, potentially involving mutations in transcriptional regulators or phage receptors. Vibrio species have been particularly useful for studying the orchestrated metabolic responses of Gram-negative marine bacteria in various challenges. In a previous study, we demonstrated that Vibrio alginolyticus downregulates the expression of specific receptors and transporters in its membrane, which may enable the bacterium to evade infection by lytic bacteriophages. In our current study, our objective was to explore how the development of bacteriophage resistance in Vibrio species disrupts the quorum-sensing cascade, subsequently affecting bacterial physiology and metabolic capacity. Using a real-time quantitative PCR (rt-QPCR) platform, we examined the expression pattern of quorum-sensing genes, auto-inducer biosynthesis genes, and cell density regulatory proteins in phage-resistant strains. Our results revealed that bacteriophage-resistant bacteria downregulate the expression of quorum-sensing regulatory proteins, such as LuxM, LuxN, and LuxP. This downregulation attenuates the normal perception of quorum-sensing peptides and subsequently diminishes the expression of cell density regulatory proteins, including LuxU, aphA, and LuxR. These findings align with the diverse phenotypic traits observed in the phage-resistant strains, such as altered biofilm formation, reduced planktonic growth, and reduced virulence. Moreover, the transcriptional depletion of aphA, the master regulator associated with low cell density, was linked to the downregulation of genes related to virulence. This phenomenon appears to be phage-specific, suggesting a finely tuned metabolic adaptation driven by phage-host interaction. These findings contribute to our understanding of the role of Vibrio species in microbial marine ecology and highlight the complex interplay between phage resistance, quorum sensing, and bacterial physiology.202337764117
9170160.9998It is the time for quorum sensing inhibition as alternative strategy of antimicrobial therapy. Multiple drug resistance poses a significant threat to public health worldwide, with a substantial increase in morbidity and mortality rates. Consequently, searching for novel strategies to control microbial pathogenicity is necessary. With the aid of auto-inducers (AIs), quorum sensing (QS) regulates bacterial virulence factors through cell-to-cell signaling networks. AIs are small signaling molecules produced during the stationary phase. When bacterial cultures reach a certain level of growth, these molecules regulate the expression of the bound genes by acting as mirrors that reflect the inoculum density.Gram-positive bacteria use the peptide derivatives of these signaling molecules, whereas Gram-negative bacteria use the fatty acid derivatives, and the majority of bacteria can use both types to modulate the expression of the target gene. Numerous natural and synthetic QS inhibitors (QSIs) have been developed to reduce microbial pathogenesis. Applications of QSI are vital to human health, as well as fisheries and aquaculture, agriculture, and water treatment. Video Abstract.202337316831
8241170.9998Molecular mechanisms of N-acyl homoserine lactone signals perception by plants. N-acyl homoserine lactones (AHLs) belong to the class of bacterial quorum sensing signal molecules involved in distance signal transduction between Gram-negative bacteria colonizers of the rhizosphere, as well as bacteria and plants. AHLs synchronize the activity of genes from individual cells, allowing the bacterial population to act as a multicellular organism, and establish a symbiotic or antagonistic relationship with the host plant. Although the effect of AHLs on plants has been studied for more than ten years, the mechanisms of plant perception of AHL signals are not fully understood. The specificity of the reactions caused by AHL indicates the existence of appropriate mechanisms for their perception by plants. In the current review, we summarize available data on the molecular mechanisms of AHL-signal perception in plants, its effect on plant growth, development, and stress resistance. We describe the latest research demonstrating direct (on plants) and indirect (on rhizosphere microflora) effects of AHLs, as well as the prospects of using these compounds in biotechnology to increase plant resistance to biotic and abiotic stresses.202234937124
8344180.9998Role of environmental stresses in elevating resistance mutations in bacteria: Phenomena and mechanisms. Mutations are an important origin of antibiotic resistance in bacteria. While there is increasing evidence showing promoted resistance mutations by environmental stresses, no retrospective research has yet been conducted on this phenomenon and its mechanisms. Herein, we summarized the phenomena of stress-elevated resistance mutations in bacteria, generalized the regulatory mechanisms and discussed the environmental and human health implications. It is shown that both chemical pollutants, such as antibiotics and other pharmaceuticals, biocides, metals, nanoparticles and disinfection byproducts, and non-chemical stressors, such as ultraviolet radiation, electrical stimulation and starvation, are capable of elevating resistance mutations in bacteria. Notably, resistance mutations are more likely to occur under sublethal or subinhibitory levels of these stresses, suggesting a considerable environmental concern. Further, mechanisms for stress-induced mutations are summarized in several points, namely oxidative stress, SOS response, DNA replication and repair systems, RpoS regulon and biofilm formation, all of which are readily provoked by common environmental stresses. Given bacteria in the environment are confronted with a variety of unfavorable conditions, we propose that the stress-elevated resistance mutations are a universal phenomenon in the environment and represent a nonnegligible risk factor for ecosystems and human health. The present review identifies a need for taking into account the pollutants' ability to elevate resistance mutations when assessing their environmental and human health risks and highlights the necessity of including resistance mutations as a target to prevent antibiotic resistance evolution.202235691443
9622190.9998Stable Neutralization of a Virulence Factor in Bacteria Using Temperate Phage in the Mammalian Gut. Elimination or alteration of select members of the gut microbiota is key to therapeutic efficacy. However, the complexity of these microbial inhabitants makes it challenging to precisely target bacteria. Here, we deliver exogenous genes to specific bacteria by genomic integration of temperate phage for long-lasting modification. As a real-world therapeutic test, we engineered λ phage to transcriptionally repress Shiga toxin by using genetic hybrids between λ and other lambdoid phages to overcome resistance encoded by the virulence-expressing prophage. We show that a single dose of engineered phage propagates throughout the bacterial community and reduces Shiga toxin production in an enteric mouse model of infection without markedly affecting bacterial concentrations. Our work reveals a new framework for transferring functions to bacteria within their native environment.IMPORTANCE With the increasing frequency of antibiotic resistance, it is critical to explore new therapeutic strategies for treating bacterial infections. Here, we use a temperate phage, i.e., one that integrates itself into the bacterial genome, to neutralize the expression of a virulence factor by modifying bacterial function at the genetic level. We show that Shiga toxin production can be significantly reduced in vitro and in the mammalian gut. Alternative to traditional applications of phage therapy that rely on killing bacteria, our genetics-based antivirulence approach introduces a new framework for treating bacterial infections.202031992629