scholarly journals Biofilm Targeting Strategy in the Eradication of Burkholderia Infections: A Mini-Review

2021 ◽  
Vol 15 (1) ◽  
pp. 51-57
Author(s):  
Wani D. Gunardi ◽  
Kris H. Timotius ◽  
Agustine Natasha ◽  
Paulina R. Evriarti
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
The Novel ◽  
Novel Therapy ◽  
Component Systems ◽  
Associated Proteins ◽  
Two Component Systems ◽  
Targeting Strategy ◽  
Immunological System

Burkholderia are intracellular pathogenic bacteria which can produce biofilm. This biofilm protects the intracellular pathogenic bacteria from antibiotic treatment and the immunological system of the host. Therefore, this review aims to describe the capacity of Burkholderia to form a biofilm, the regulation of its biofilm formation, the efficacy of antibiotics to eradicate biofilm, and the novel therapy which targets its biofilm. Burkholderia's biofilm is characterized by its lipopolysaccharides, exopolysaccharides (EPSs), biofilm-associated proteins, and eDNA. Its regulation is made by quorum sensing, c-di-AMP, sRNA, and two component systems. Many antibiotics have been used as sole or mixture agents; however, they are not always effective in eradicating the biofilm-forming Burkholderia. Inhibitors of quorum sensing and other non-conventional antibiotic approaches are promising to discover effective treatment of Burkholderia infections.

scholarly journals Pangenome Analytics Reveal Two-Component Systems as Conserved Targets in ESKAPEE Pathogens

mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Akanksha Rajput ◽  
Yara Seif ◽  
Kumari Sonal Choudhary ◽  
Christopher Dalldorf ◽  
Saugat Poudel ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Drug Targets ◽  
Pathogenic Bacteria ◽  
Content Type ◽  
Vital Functions ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

ABSTRACT The two-component system (TCS) helps bacteria sense and respond to environmental stimuli through histidine kinases and response regulators. TCSs are the largest family of multistep signal transduction processes, and they are involved in many important cellular processes such as antibiotic resistance, pathogenicity, quorum sensing, osmotic stress, and biofilms. Here, we perform the first comprehensive study to highlight the role of TCSs as potential drug targets against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli) pathogens through annotation, mapping, pangenomic status, gene orientation, and sequence variation analysis. The distribution of the TCSs is group specific with regard to Gram-positive and Gram-negative bacteria, except for KdpDE. The TCSs among ESKAPEE pathogens form closed pangenomes, except for Pseudomonas aeruginosa. Furthermore, their conserved nature due to closed pangenomes might make them good drug targets. Fitness score analysis suggests that any mutation in some TCSs such as BaeSR, ArcBA, EvgSA, and AtoSC, etc., might be lethal to the cell. Taken together, the results of this pangenomic assessment of TCSs reveal a range of strategies deployed by the ESKAPEE pathogens to manifest pathogenicity and antibiotic resistance. This study further suggests that the conserved features of TCSs might make them an attractive group of potential targets with which to address antibiotic resistance. IMPORTANCE The ESKAPEE pathogens are the leading cause of health care-associated infections worldwide. Two-component systems (TCSs) can be used as effective targets against pathogenic bacteria since they are ubiquitous and manage various vital functions such as antibiotic resistance, virulence, biofilms, quorum sensing, and pH balance, among others. This study provides a comprehensive overview of the pangenomic status of the TCSs among ESKAPEE pathogens. The annotation and pangenomic analysis of TCSs show that they are significantly distributed and conserved among the pathogens, as most of them form closed pangenomes. Furthermore, our analysis also reveals that the removal of the TCSs significantly affects the fitness of the cell. Hence, they may be used as promising drug targets against bacteria.

scholarly journals Multiple Mechanisms of Action for Inhibitors of Histidine Protein Kinases from Bacterial Two-Component Systems

1999 ◽  
Vol 43 (7) ◽  
pp. 1693-1699 ◽  
Author(s):  
Jamese J. Hilliard ◽  
Raul M. Goldschmidt ◽  
Lisa Licata ◽  
Ellen Z. Baum ◽  
Karen Bush
Keyword(s):  
Pathogenic Bacteria ◽  
Response Regulator ◽  
Membrane Integrity ◽  
Bacterial Killing ◽  
Gram Positive Bacteria ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems ◽  
Bacterial Cell Membrane ◽  
Cellular Incorporation

ABSTRACT Many pathogenic bacteria utilize two-component systems consisting of a histidine protein kinase (HPK) and a response regulator (RR) for signal transduction. During the search for novel inhibitors, several chemical series, including benzoxazines, benzimidazoles, bis-phenols, cyclohexenes, trityls, and salicylanilides, were identified that inhibited the purified HPK-RR pairs KinA-Spo0F and NRII-NRI, with 50% inhibitory concentrations (IC50s) ranging from 1.9 to >500 μM and MICs ranging from 0.5 to >16 μg/ml for gram-positive bacteria. However, additional observations suggested that mechanisms other than HPK inhibition might contribute to antibacterial activity. In the present work, representative compounds from the six different series of inhibitors were analyzed for their effects on membrane integrity and macromolecular synthesis. At 4× MIC, 17 of 24 compounds compromised the integrity of the bacterial cell membrane within 10 min, as measured by uptake of propidium iodide. In this set, compounds with lower IC50s tended to cause greater membrane disruption. Eleven of 12 compounds inhibited cellular incorporation of radiolabeled thymidine and uridine >97% in 5 min and amino acids >80% in 15 min. The HPK inhibitor that allowed >25% precursor incorporation had no measurable MIC (>16 μg/ml). Fifteen of 24 compounds also caused hemolysis of equine erythrocytes. Thus, the antibacterial HPK inhibitors caused a rapid decrease in cellular incorporation of RNA, DNA, and protein precursors, possibly as a result of the concomitant disruption of the cytoplasmic membrane. Bacterial killing by these HPK inhibitors may therefore be due to multiple mechanisms, independent of HPK inhibition.

scholarly journals Anti-quorum Sensing Potential of Ageratum Conyzoides L. (Asteraceae) Extracts

2021 ◽  
Author(s):  
Eli COMPAORE ◽  
Moussa COMPAORE ◽  
Vincent OUEDRAOGO ◽  
Ablassé ROUAMBA ◽  
Martin KIENDREBEOGO
Keyword(s):  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Methanolic Extract ◽  
Negative Impact ◽  
Significant Inhibition ◽  
High Morbidity ◽  
Ageratum Conyzoides ◽  
Phytochemical Content

Abstract Background: Pseudomonas aeruginosa causes infections in human particularly immunocompromised patients with cystic fibrosis, severe burns and HIV, resulting in high morbidity and mortality. The pathogenic bacteria P aeruginosa produces virulence factors regulated by the mechanism called quorum sensing system. Objective: The aim of this study was to assess the anti-quorum sensing activity of Ageratum conyzoides extracts Method: Chromobacterium violaceum reporter strain CV026 was used to highlight any interference with bacterium QS and strains derived from P. aeruginosa PAO1 were used to reveal any interference with the expression of quorum sensing genes, and to assess any impact of extract on the kinetics of the production of pyocyanin, elastases and biofilm formation. Results: Hydro-methanolic extract at the sub-inhibitory concentration of 100 μg/mL reduced quorum sensing virulence factors production such as, pyocyanin, elastases, rhamnolipids and biofilm formation in P. aeruginosa PAO1 after 18 hours monitoring. Extract showed significant inhibition in HSL-mediated violacein production on C. violaceum CV026 after 48 hours monitoring. Biofilm formation was inhibited up to 32%. It affected QS gene expression in PAO1. The regulatory genes lasR / rhlR and the lasI synthases were most affected. At 8hours, hydro-methanolic extract reduced both QS gene to more than 30% (lasI/lasR and rhlI/R respectively 33.8% /30.2% and 36% /33.2%). RhlA and lasB genes have been relatively affected (13.4% and 28.9%). After 18 h, this extract reduced significantly the expression of regulatory 30 genes lasR (31%) and rhlR (39.6%) although synthases genes seemed to be less affected (lasI/21.2% and rhlI/11.6%). A limited impact was observed on the downstream genes (lasB /20.0% and rhlA /15.3%). No negative impact was observed on CV026 and PAO1 growth and cell viability. Our study also showed that A. conyzoides having ample amount of phenolics, flavonoids and triterpenoids. This phytochemical content could be one of the factors for showing anti quorum potential. Conclusion: Results indicate that hydro methanol 80 % extract from A. conyzoides could be a source of potential QS inhibition compounds.

scholarly journals Two Component Regulatory Systems and Antibiotic Resistance in Gram-Negative Pathogens

2019 ◽  
Vol 20 (7) ◽  
pp. 1781 ◽  
Author(s):  
Anjali Y. Bhagirath ◽  
Yanqi Li ◽  
Rakesh Patidar ◽  
Katherine Yerex ◽  
Xiaoxue Ma ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Pathogenic Bacteria ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Gram Negative ◽  
Environmental Signals ◽  
Component Systems ◽  
Two Component ◽  
Two Component Systems

Gram-negative pathogens such as Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are the leading cause of nosocomial infections throughout the world. One commonality shared among these pathogens is their ubiquitous presence, robust host-colonization and most importantly, resistance to antibiotics. A significant number of two-component systems (TCSs) exist in these pathogens, which are involved in regulation of gene expression in response to environmental signals such as antibiotic exposure. While the development of antimicrobial resistance is a complex phenomenon, it has been shown that TCSs are involved in sensing antibiotics and regulating genes associated with antibiotic resistance. In this review, we aim to interpret current knowledge about the signaling mechanisms of TCSs in these three pathogenic bacteria. We further attempt to answer questions about the role of TCSs in antimicrobial resistance. We will also briefly discuss how specific two-component systems present in K. pneumoniae, A. baumannii, and P. aeruginosa may serve as potential therapeutic targets.

scholarly journals The Formation of Biofilms byPseudomonas aeruginosa: A Review of the Natural and Synthetic Compounds Interfering with Control Mechanisms

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Tsiry Rasamiravaka ◽  
Quentin Labtani ◽  
Pierre Duez ◽  
Mondher El Jaziri
Keyword(s):  
Biofilm Formation ◽  
Immune Defense ◽  
Natural Resistance ◽  
Control Mechanisms ◽  
Chronic Infections ◽  
Complex Biological System ◽  
Component Systems ◽  
Two Component Systems ◽  
Opportunistic Pathogenic ◽  
Natural And Synthetic

P. aeruginosais an opportunistic pathogenic bacterium responsible for both acute and chronic infections. Beyond its natural resistance to many drugs, its ability to form biofilm, a complex biological system, renders ineffective the clearance by immune defense systems and antibiotherapy. The objective of this report is to provide an overview (i) onP. aeruginosabiofilm lifestyle cycle, (ii) on the main key actors relevant in the regulation of biofilm formation byP. aeruginosaincluding QS systems,GacS/GacAandRetS/LadStwo-component systems and C-di-GMP-dependent polysaccharides biosynthesis, and (iii) finally on reported natural and synthetic products that interfere with control mechanisms of biofilm formation byP. aeruginosawithout affecting directly bacterial viability. Concluding remarks focus on perspectives to consider biofilm lifestyle as a target for eradication of resistant infections caused byP. aeruginosa.

scholarly journals Mitigation of acyl-homoserine lactone (AHL) based bacterial quorum sensing, virulence functions, and biofilm formation by yttrium oxide core/shell nanospheres: Novel approach to combat drug resistance

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fohad Mabood Husain ◽  
Anees A. Ansari ◽  
Aslam Khan ◽  
Naushad Ahmad ◽  
Abdulrahman Albadri ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Photoelectron Spectroscopy ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Core Shell ◽  
Sem Images ◽  
Biofilm Inhibition ◽  
X Ray ◽  
Average Grain Size ◽  
The Impact

AbstractThe present study evaluated the efficacy of Y2O3:Tb (core) and Y2O3:Tb@SiO2 nanospheres (core/shell NSs) against virulence functions regulated by quorum sensing (QS) and biofilm formation in pathogenic bacteria. Scanning electron microscope (SEM) images were used to study the size, shape, and morphology. The images clearly displayed spherical shaped, mono-dispersed particles with narrow size distribution and an average grain size of 110–130 nm. The chemical composition of the samples was determined by using energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS). We determined the impact of core and core/shell NSs on QS using sensor strains of Chromobacterium violaceum CVO26 and Pseudomonas aeruginosa PAO1 in a comparative study. Sub-MICs of core and core/shell NSs substantially suppressed QS-controlled violacein production in C. violaceum. Similar concentration-dependent effect of sub-MICs of synthesized core and core/shell NSs was observed in the QS-regulated virulence functions (elastase, total protease, pyocyanin production, swarming motility, and exopolysaccharide production) in PAO1. A concentration-dependent decrease (14–60%) was recorded in the biofilm forming capability of PAO1, upon treatment with core and core/shell NSs. Moreover, core/shell NSs were more effective in inhibiting biofilm at higher tested concentrations as compared to core-NSs. The synthesized NSs demonstrated significantly impaired attachment of cells to the microtiter plate indicating that NSs target biofilm inhibition at the attachment stage. Based on these results, we predict that core and core/shell NSs may be an alternative to combat the threat of drug-resistant pathogenic bacteria.

scholarly journals Genome-Wide Mapping Reveals Complex Regulatory Activities of BfmR in Pseudomonas aeruginosa

2021 ◽  
Vol 9 (3) ◽  
pp. 485
Author(s):  
Ke Fan ◽  
Qiao Cao ◽  
Lefu Lan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Chromatin Immunoprecipitation ◽  
Biofilm Formation ◽  
High Throughput Sequencing ◽  
Response Regulator ◽  
Cellular Functions ◽  
Genome Wide ◽  
Component Systems ◽  
Genes Encoding ◽  
Two Component Systems

BfmR is a response regulator that modulates diverse pathogenic phenotypes and induces an acute-to-chronic virulence switch in Pseudomonas aeruginosa, an important human pathogen causing serious nosocomial infections. However, the mechanisms of action of BfmR remain largely unknown. Here, using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), we showed that 174 chromosomal regions of P. aeruginosa MPAO1 genome were highly enriched by coimmunoprecipitation with a C-terminal Flag-tagged BfmR. Integration of these data with global transcriptome analyses revealed that 172 genes in 106 predicted transcription units are potential targets for BfmR. We determined that BfmR binds to and modulates the promoter activity of genes encoding transcriptional regulators CzcR, ExsA, and PhoB. Intriguingly, BfmR bound to the promoters of a number of genes belong to either CzcR or PhoB regulon, or both, indicating that CzcRS and PhoBR two-component systems (TCSs) deeply feed into the BfmR-mediated regulatory network. In addition, we demonstrated that phoB is required for BfmR to promote the biofilm formation by P. aeruginosa. These results delineate the direct BfmR regulon and exemplify the complexity of BfmR-mediated regulation of cellular functions in P. aeruginosa.

scholarly journals Quorum Sensing Inhibition or Quenching in Acinetobacter baumannii: The Novel Therapeutic Strategies for New Drug Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Shan Zhong ◽  
Songzhe He
Keyword(s):  
Quorum Sensing ◽  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Quorum Quenching ◽  
The Novel ◽  
Antimicrobial Drugs ◽  
Quorum Sensing Inhibitors ◽  
Bacterial Drug Resistance ◽  
A Cell ◽  
Novel Therapeutic Strategies

Acinetobacter baumannii is a Gram-negative opportunistic nosocomial pathogen, which can cause ventilator-related and blood infection in critically ill patients. The resistance of A. baumannii clinical isolates to common antimicrobials and their tolerance to desiccation have emerged as a serious problem to public health. In the process of pathogenesis, bacteria release signals, which regulate virulence and pathogenicity-related genes. Such bacteria coordinate their virulent behavior in a cell density-dependent phenomenon called quorum sensing (QS). In contrast, the two main approaches of QS interference, quorum sensing inhibitors (QSIs) and quorum quenching (QQ) enzymes, have been developed to reduce the virulence of bacteria, thus reducing the pressure to produce bacterial drug resistance. Therefore, QSIs or QQ enzymes, which interfere with these processes, might potentially inhibit bacterial QS and ultimately biofilm formation. In this review, we aim to describe the state-of-art in the QS process in A. baumannii and elaborate on the use of QSIs or QQ enzymes as antimicrobial drugs in various potential sites of the QS pathway.

scholarly journals Quorum Sensing Inhibition by Marine Bacteria

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 427 ◽  
Author(s):  
Anabela Borges ◽  
Manuel Simões
Keyword(s):  
Quorum Sensing ◽  
Marine Bacteria ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogenesis ◽  
First Century ◽  
Bioactive Components ◽  
Quorum Sensing Inhibition ◽  
Bacterial Communication ◽  
Alternative Approaches

Antibiotic resistance has been increasingly reported for a wide variety of bacteria of clinical significance. This widespread problem constitutes one of the greatest challenges of the twenty-first century. Faced with this issue, clinicians and researchers have been persuaded to design novel strategies in order to try to control pathogenic bacteria. Therefore, the discovery and elucidation of the mechanisms underlying bacterial pathogenesis and intercellular communication have opened new perspectives for the development of alternative approaches. Antipathogenic and/or antivirulence therapies based on the interruption of quorum sensing pathways are one of several such promising strategies aimed at disarming rather than at eradicating bacterial pathogens during the course of colonization and infection. This review describes mechanisms of bacterial communication involved in biofilm formation. An overview of the potential of marine bacteria and their bioactive components as QS inhibitors is further provided.

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