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1.
Crit Rev Microbiol ; 50(2): 168-195, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36651058

RESUMO

Present-day healthcare employs several types of invasive devices, including urinary catheters, to improve medical wellness, the clinical outcome of disease, and the quality of patient life. Among urinary catheters, the Foley catheter is most commonly used in patients for bladder drainage and collection of urine. Although such devices are very useful for patients who cannot empty their bladder for various reasons, they also expose patients to catheter-associated urinary tract infections (CAUTIs). Catheter provides an ideal surface for bacterial colonization and biofilm formation, resulting in persistent bacterial infection and severe complications. Hence, rigorous efforts have been made to develop catheters that harbour antimicrobial and anti-fouling properties to resist colonization by bacterial pathogens. In this regard, catheter modification by surface functionalization, impregnation, blending, or coating with antibiotics, bioactive compounds, and nanoformulations have proved to be effective in controlling biofilm formation. This review attempts to illustrate the complications associated with indwelling Foley catheters, primarily focussing on challenges in fighting CAUTI, catheter colonization, and biofilm formation. In this review, we also collate scientific literature on catheter modification using antibiotics, plant bioactive components, bacteriophages, nanoparticles, and studies demonstrating their efficacy through in vitro and in vivo testing.


Assuntos
Infecções Relacionadas a Cateter , Infecções Urinárias , Humanos , Infecções Relacionadas a Cateter/etiologia , Infecções Relacionadas a Cateter/microbiologia , Infecções Urinárias/prevenção & controle , Cateteres Urinários/efeitos adversos , Cateteres Urinários/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Bactérias
2.
Microb Pathog ; 186: 106485, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38052279

RESUMO

Lumpy skin disease (LSD) is an emerging transboundary viral disease of livestock animals which was first reported in 1929 in Zambia. Although LSD is a neglected disease of economic importance, it extends a direct impact on the international trade and economy in livestock-dependent countries. Lumpy skin disease virus (LSDV) has been endemic in African countries, where several outbreaks have been reported previously. However, the virus has spread rapidly across the Middle East in the past two decades, reaching Russia and, recently, the Asian subcontinent. With unprecedented cluster outbreaks being reported across Asian countries like India, China, Nepal, Bangladesh, and Pakistan, LSDV is certainly undergoing an epidemiological shift and expanding its geographical footprint worldwide. Due to high mortality among livestock animals, the recent LSD outbreaks have gained attention from global regulatory authorities and raised serious concerns among epidemiologists and veterinary researchers. Despite networked global surveillance of the disease, recurrent LSD cases pose a threat to the livestock industry. Hence, this review provides recent insights into the LSDV biology by augmenting the latest literature associated with its pathogenesis, transmission, current intervention strategies, and economic implications. The review critically examines the changing epidemiological footprint of LSDV globally, especially in relation to developing countries of the Asian subcontinent. We also speculate the possible reasons contributing to the ongoing LSD outbreaks, including illegal animal trade, climate change, genetic recombination events between wild-type and vaccine strains, reversion of vaccine strains to virulent phenotype, and deficiencies in active monitoring during the COVID-19 pandemic.


Assuntos
Doença Nodular Cutânea , Vírus da Doença Nodular Cutânea , Animais , Bovinos , Humanos , Doença Nodular Cutânea/epidemiologia , Doença Nodular Cutânea/prevenção & controle , Comércio , Pandemias , Internacionalidade , Vírus da Doença Nodular Cutânea/genética , Surtos de Doenças/veterinária , Vacinas Atenuadas , Paquistão , Filogenia
3.
Microb Pathog ; 186: 106468, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38036112

RESUMO

Pseudomonas aeruginosa has emerged as a critical superbug that poses a serious threat to public health. Owing to its virulence and multidrug resistance profiles, the pathogen demands immediate attention for devising alternate intervention strategies. In an attempt to repurpose drugs against P. aeruginosa, this preclinical study was aimed at investigating the antivirulence prospects of albendazole (AbZ), an FDA-approved anti-helminthic drug, recently predicted to disrupt quorum sensing (QS) in Chromobacterium violaceum. AbZ was scrutinized for its quorum quenching (QQ) prospects, effect on bacterial virulence, different motility phenotypes, and biofilm formation in vitro. Additionally, in silico analysis was employed to predict the molecular interactions between AbZ and QS receptors. At sub-inhibitory levels, AbZ demonstrated anti-QS activity and significantly abrogated AHL biosynthesis in P. aeruginosa. Moreover, AbZ significantly downregulated the transcript levels of QS- (lasI/lasR, rhlI/rhlR, and pqsA/pqsR) and QS-dependent virulence (aprA, lasA, lasB, plcH, and toxA) genes in P. aeruginosa. This coincided with reduced hemolysin, alginate, pyocyanin, rhamnolipids, total protease, and elastase production, thereby lowering phenotypic virulence. Molecular docking with AbZ further revealed strong associations and high binding energies with LasR (-8.8 kcal/mol), RhlR (-6.5 kcal/mol), and PqsR (-6.3 kcal/mol) receptors. AbZ also impeded bacterial motility and abolished EPS production, severely compromising pseudomonal biofilm formation. For the first time, AbZ was shown to interfere with QS circuitry and consequently disarming pseudomonal virulence. Hence, AbZ can be exploited for its antivirulence properties against P. aeruginosa.


Assuntos
Infecções por Pseudomonas , Percepção de Quorum , Humanos , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Pseudomonas aeruginosa , Biofilmes , Albendazol/farmacologia , Reposicionamento de Medicamentos , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Antibacterianos/química , Infecções por Pseudomonas/microbiologia , Proteínas de Bactérias/metabolismo
4.
Future Microbiol ; 18: 1339-1351, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37962488

RESUMO

Aim: The efficacy of a pyochelin-zingerone conjugate (PZC) against Pseudomonas aeruginosa in vivo in a mouse model of peritonitis, as well as mode of action in vitro, were investigated. Methods & results: Intraperitoneal administration of PZC (220 mg kg-1 b.wt.) resulted in a significant reduction in bacterial count in liver tissue by 2 log10 on the 4th day post infection. This was supported by reduced levels of inflammatory markers, liver function, inflammatory cytokines and improved histopathology. PZC showed its ability to disrupt the cellular membrane, increase permeability of the membrane and leakage of intracellular contents of P. aeruginosa, resulting in its death. Conclusion: The present study reports the hepatoprotective potential of PZC in an experimental model of P. aeruginosa-induced peritonitis.


Assuntos
Peritonite , Infecções por Pseudomonas , Animais , Camundongos , Pseudomonas aeruginosa , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Peritonite/patologia , Fenóis/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia
5.
Microb Pathog ; 183: 106281, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37541553

RESUMO

Metformin (MeT) is an FDA-approved drug with a myriad of health benefits. Besides being used as an anti-diabetic drug, MeT is also effective against various cancers, liver-, cardiovascular-, and renal diseases. This study was undertaken to examine its unique potential as an anti-virulence drug against an opportunistic bacterial pathogen, Pseudomonas aeruginosa. Due to the menace of multidrug resistance in pathogenic microorganisms, many novel or repurposed drugs with anti-virulence prospects are emerging as next-generation therapies with the aim to overshadow the application of existing antimicrobial regimens. The quorum sensing (QS) mechanisms of P. aeruginosa are an attractive drug target for attenuating bacterial virulence. In this context, the anti-QS potential of MeT was scrutinized using biosensor assays. MeT was comprehensively evaluated for its effects on different motility phenotypes, virulence factor production (phenotypic and genotypic expression) along with biofilm development in P. aeruginosa in vitro. At sub-lethal concentrations, MeT displayed prolific quorum quenching (QQ) ability and remarkably inhibited AHL biosynthesis in P. aeruginosa. Moreover, MeT (1/8 MIC) effectively downregulated the expression levels of various QS- and virulence genes in P. aeruginosa, which coincided with a notable reduction in the levels of alginate, hemolysin, pyocyanin, pyochelin, elastase, and protease production. In silico analysis through molecular docking also predicted strong associations between MeT and QS receptors of P. aeruginosa. MeT also compromised the motility phenotypes and successfully abrogated biofilm formation by inhibiting EPS production in P. aeruginosa. Hence, MeT may be repurposed as an anti-virulence drug against P. aeruginosa in clinical settings.


Assuntos
Metformina , Pseudomonas aeruginosa , Simulação de Acoplamento Molecular , Metformina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Virulência/genética , Biofilmes , Percepção de Quorum , Fatores de Virulência/metabolismo
6.
Future Microbiol ; 18: 443-459, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37317864

RESUMO

Despite achieving unparalleled progress in the field of science and technology, the global health community is still threatened by the looming pressure of infectious diseases. One of the greatest challenges is the rise in infections by antibiotic-resistant microorganisms. The misuse of antibiotics has led to the present circumstances, and there is seemingly no solution. There is imminent pressure to develop new antibacterial therapies to curb the rise and spread of multidrug resistance. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, having immense potential as a gene-editing tool, has gained considerable attention as an alternative antibacterial therapy. Strategies, aiming to either eliminate pathogenic strains or to restore sensitivity to antibiotics, are the main focus of research. This review deals with the development of CRISPR-Cas antimicrobials and their delivery challenges.


Bacteria resistant to drugs have become a major global health problem. Infections caused by resistant bacteria have many social and economic consequences, particularly in low- and middle-income countries. The WHO has estimated that 10 million people will die every year due to drug resistance by 2050. Due to the lengthy amount of time and high costs of developing new drugs, we must explore alternatives. One such alternative includes clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, a tool with the ability to edit the genetic material of bacteria. CRISPR-Cas can restore sensitivity to drugs as well as kill bacteria.


Assuntos
Antibacterianos , Sistemas CRISPR-Cas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Edição de Genes , Sistema Imunitário
7.
ACS Omega ; 8(24): 21391-21409, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37360468

RESUMO

Biofilm-associated infections have emerged as a significant public health challenge due to their persistent nature and increased resistance to conventional treatment methods. The indiscriminate usage of antibiotics has made us susceptible to a range of multidrug-resistant pathogens. These pathogens show reduced susceptibility to antibiotics and increased intracellular survival. However, current methods for treating biofilms, such as smart materials and targeted drug delivery systems, have not been found effective in preventing biofilm formation. To address this challenge, nanotechnology has provided innovative solutions for preventing and treating biofilm formation by clinically relevant pathogens. Recent advances in nanotechnological strategies, including metallic nanoparticles, functionalized metallic nanoparticles, dendrimers, polymeric nanoparticles, cyclodextrin-based delivery, solid lipid nanoparticles, polymer drug conjugates, and liposomes, may provide valuable technological solutions against infectious diseases. Therefore, it is imperative to conduct a comprehensive review to summarize the recent advancements and limitations of advanced nanotechnologies. The present Review encompasses a summary of infectious agents, the mechanisms that lead to biofilm formation, and the impact of pathogens on human health. In a nutshell, this Review offers a comprehensive survey of the advanced nanotechnological solutions for managing infections. A detailed presentation has been made as to how these strategies may improve biofilm control and prevent infections. The key objective of this Review is to summarize the mechanisms, applications, and prospects of advanced nanotechnologies to provide a better understanding of their impact on biofilm formation by clinically relevant pathogens.

8.
Future Microbiol ; 18: 43-63, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36537228

RESUMO

Chronic skin wound infections are inextricably linked with high mortality rates. With the rise in the aging population and the threat of diabetes, obesity and lifestyle-based diseases, the risk incurred from invasive wound pathogens has been ever escalating. Thus, more efficacious wound care management is necessary to cope with such morbid illnesses. A plethora of bioactive agents, such as antibiotics, phytochemicals, essential oils, phages among others, has been exploited to develop wound dressings, raising tremendous interest in their prospective use as wound care products. The present review critically focuses on the therapeutic implications of advanced wound dressings that have assisted in the expansion of regenerative medicine and also discusses the practical concerns that have limited their bench-to-market entry.


Assuntos
Bandagens , Cicatrização , Antibacterianos
9.
Molecules ; 27(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36364411

RESUMO

Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum sensing (QS) to regulate cellular interactions via small chemical signaling molecules which also help with adaptation under undesirable survival conditions. Proteobacteria use acyl-homoserine lactone (AHL) molecules as autoinducers to sense population density and modulate gene expression. The LuxI-type enzymes synthesize AHL molecules, while the LuxR-type proteins (AHL transcriptional regulators) bind to AHLs to regulate QS-dependent gene expression. Diverse AHLs have been identified, and the diversity extends to AHL synthases and AHL receptors. This review comprehensively explains the molecular diversity of AHL signaling components of Pseudomonas aeruginosa, Chromobacterium violaceum, Agrobacterium tumefaciens, and Escherichia coli. The regulatory mechanism of AHL signaling is also highlighted in this review, which adds to the current understanding of AHL signaling in Gram-negative bacteria. We summarize molecular diversity among well-studied QS systems and recent advances in the role of QS proteins in bacterial cellular signaling pathways. This review describes AHL-dependent QS details in bacteria that can be employed to understand their features, improve environmental adaptation, and develop broad biomolecule-based biotechnological applications.


Assuntos
Acil-Butirolactonas , Percepção de Quorum , Humanos , Pseudomonas aeruginosa/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Bactérias Gram-Negativas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
10.
Environ Microbiol ; 24(10): 4547-4560, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35974453

RESUMO

Just when the world started to adapt to the 'new normal' amid the coronavirus disease 19 (COVID-19) pandemic, the world is witnessing the wrath of another viral disease, the monkeypox virus (MPXV). The virus is endemic to African countries, where several outbreaks have been reported in the past. However, the present cases have been reported in non-endemic countries worldwide. Although MPX is considered to be a self-limiting disease, recent reports on its incidence have proved otherwise. The 2022 multi-country MPX outbreak has drawn the attention of global surveillance organizations and epidemiologists to trace its origin; however, there are existing gaps regarding the animal reservoirs, biological implications, and management of MPX. In view of the recent events, the World Health Organization (WHO) has also declared the ongoing MPX outbreak a global health emergency. Hence, the geographically expanding MPXV poses a significant threat to human health and public safety. In this review, the latest insights into the biology of MPXV have been provided by discussing its biological implications on human health, changing epidemiological footprint, and presently available intervention strategies. This review also sheds light on the existing lacunas and possible reasons that may have been responsible for the ongoing MPX outbreak.


Assuntos
COVID-19 , Mpox , Animais , COVID-19/epidemiologia , Surtos de Doenças , Humanos , Mpox/epidemiologia , Monkeypox virus/genética , Pandemias
11.
J Appl Microbiol ; 133(4): 2235-2254, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35984044

RESUMO

AIM: The present study aims to investigate the antimicrobial as well as antivirulence potential and the principle mechanism of action of guaiacol against Pseudomonas aeruginosa. METHODS AND RESULTS: Quorum sensing inhibition and membrane disruption studies were performed to check the effect of guaiacol on the virulence of P. aeruginosa. Production of various virulence factors and biofilm formation was studied at a sub-MIC concentration of guaiacol alone (1/8 MIC) and in combination with ciprofloxacin (1/2 FIC). Guaiacol exhibited synergistic interactions with ciprofloxacin and further reduced the production of all virulence factors and biofilm formation. Using crystal violet (CV) assay and quantification of exopolysaccharide, we observed weak biofilm formation, together with reduced motilities at sub-MIC, which was further visualized by confocal laser microscopy and Field Emission Scanning Electron Microscopy. The antibacterial activity of guaiacol against P. aeruginosa upon 2 × MIC exposure coincided with enhanced membrane permeability leading to disruption and release of cellular material as quantified by CV uptake assay and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The results demonstrated that sub-MICs of guaiacol in combination with ciprofloxacin can act as a potent alternate compound for attenuation of quorum sensing in P. aeruginosa. CONCLUSION: The study reports that guaiacol in combination with ciprofloxacin at 1/2 FIC significantly compromised the bacterial growth and motilities alongside inducing quorum quenching potential. This was accompanied by inhibition of biofilm which subsequently decreased EPS production at sub-MIC concentration. Furthermore, guaiacol in combination displayed a severe detrimental effect on bacterial membrane disruption, thereby enhancing cellular material release. NOVELTY IMPACT STATEMENT: For the first time, the potential of guaiacol in combination with ciprofloxacin in attenuation of virulence factors, and biofilm formation in Pseudomonas aeruginosa was described. Results corroborate how plant bioactive in synergism with antibiotics can act as an alternate treatment regime to tackle the menace of drug resistance.


Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Antibacterianos/farmacologia , Biofilmes , Ciprofloxacina/farmacologia , Violeta Genciana/farmacologia , Guaiacol/farmacologia , Dodecilsulfato de Sódio/farmacologia , Fatores de Virulência
12.
Front Cell Infect Microbiol ; 12: 899566, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35782125

RESUMO

The quorum sensing (QS) circuitry of Pseudomonas aeruginosa represents an attractive target to attenuate bacterial virulence and antibiotic resistance. In this context, phytochemicals harboring anti-virulent properties have emerged as an alternative medicine to combat pseudomonal infections. Hence, this study was undertaken to investigate the synergistic effects and quorum quenching (QQ) potential of cinnamaldehyde (CiNN) in combination with gentamicin (GeN) against P. aeruginosa. The QQ activity of this novel combination was evaluated using a QS reporter strain and synergism was studied using chequerboard assays. Further, the genotypic and phenotypic expression of pseudomonal virulence factors was examined alongside biofilm formation. The combination of CiNN and GeN exhibited synergy and promising anti-QS activity. This drug combination was shown to suppress AHL production and downregulate the expression of critical QS genes in P. aeruginosa PAO1. Molecular docking revealed strong interactions between the QS receptors and CiNN, asserting its QQ potential. Bacterial motility was compromised along with a significant reduction in pyocyanin (72.3%), alginate (58.7%), rhamnolipid (33.6%), hemolysin (82.6%), protease (70.9%), and elastase (63.9%) production. The drug combination successfully eradicated preformed biofilms and inhibited biofilm formation by abrogating EPS production. Our findings suggest that although GeN alone could not attenuate QS, but was able to augment the anti-QS potential of CiNN. To validate our results using an infection model, we quantified the survival rates of Caenorhabditis elegans following PAO1 challenge. The combination significantly rescued C. elegans from PAO1 infection and improved its survival rate by 54% at 96 h. In summary, this study is the first to elucidate the mechanism behind the QQ prospects of CiNN (augmented in presence of GeN) by abrogating AHL production and increasing the survival rate of C. elegans, thereby highlighting its anti-virulent properties.


Assuntos
Infecções por Pseudomonas , Acroleína/análogos & derivados , Animais , Caenorhabditis elegans , Gentamicinas , Simulação de Acoplamento Molecular , Pseudomonas aeruginosa , Percepção de Quorum
13.
Front Chem ; 10: 902719, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783213

RESUMO

To address the issue of multidrug resistance in Pseudomonas aeruginosa, a novel catechol-zingerone conjugate (1) linked via a non-hydrolyzable 1,2,3-triazole linker was synthesized and subjected to biological evaluation based on the Trojan horse strategy. To enhance the efficacy, catechol, a xenosiderophore, utilized by P. aeruginosa for iron assimilation, and the dietary phytochemical zingerone, known for its anti-virulent activity against Pseudomonas aeruginosa, were exploited in the present study. Theoretical validation of conjugate (1) was conducted by in silico molecular docking analysis to determine the interaction with outer membrane transport receptor PirA and quorum sensing signal receptors. In addition, nine-fold binding affinity of Conjugate (1) toward PirA (5FP2) in comparison to its natural ligand catechol with D-score -1.13 Å authenticated the designed Trojan horse drug. Conjugate (1) showed stronger anti-virulent activity than zingerone; hence, it exhibited a promising anti-biofilm efficacy as assessed by crystal violet assay and visualized by FESEM toward P. aeruginosa. Encouraging results against P. aeruginosa in terms of quorum sensing regulated virulence factors, motility phenotypes, and biofilm formation with no cell cytotoxicity and could help open hitherto unexplored possibilities of establishing Trojan horse drugs as a successful approach against multidrug resistance in P. aeruginosa.

14.
Folia Microbiol (Praha) ; 67(6): 837-850, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35854181

RESUMO

Clustered regularly interspaced short palindromic repeats and associated Cas proteins (CRISPR-Cas) are the only known adaptive immune system in prokaryotes. CRISPR-Cas system provides sequence-specific immunity against invasion by foreign genetic elements. It carries out its functions by incorporating a small part of the invading DNA sequence, termed as spacer into the CRISPR array. Although the CRISPR-Cas systems are mainly responsible for adaptive immune functions, their alternative role in the gene regulation, bacterial pathophysiology, virulence, and evolution has started to unravel. In several species, these systems are revealed to regulate the processes beyond adaptive immunity by employing various components of CRISPR-Cas machinery, independently or in combination. The molecular mechanisms entailing the regulatory processes are not clear in most of the instances. In this review, we have discussed some well-known and some recently established noncanonical functions of CRISPR-Cas system and its fast-extending applications in other biological processes.


Assuntos
Fenômenos Biológicos , Sistemas CRISPR-Cas , Archaea , Bactérias/genética , Virulência
16.
3 Biotech ; 12(6): 133, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35615747

RESUMO

Disruption of quorum sensing (QS) system, which is a central regulator for pathogenesis of Pseudomonas aeruginosa, is referring to as quorum quenching (QQ). This study was undertaken to evaluate and enhance the anti-quorum sensing (AQS) potential of probiotic strain Lactobacillus rhamnosus GG. The cell-free supernatant (CFS) of this probiotic strain showed anti-quorum sensing activity against Pseudomonas aeruginosa, which was determined using well-diffusion agar-plate assay. Anti-quorum sensing potential of L. rhamnosus GG was enhanced by optimization of various cultural conditions using classical and statistical optimization approaches. Six variables were optimized using one-variable-at-a-time (OVAT) method. Four significant variables, viz., temperature, pH, incubation time, metal ion, and its concentration, were chosen for further optimization by response surface methodology (RSM) using central composite design (CCD). Analysis of variance (ANOVA) demonstrated that the regression model is highly significant, as indicated by F test with a low probability value (p  < 0.0002) and high value of coefficient of determination (0.8738) and also had significant influence on the generation of anti-quorum sensing effector molecules. Maximum production of anti-quorum sensing activity, in terms of zones of inhibition, was achieved under the following optimized conditions such as 37 °C temperature, pH 6.5, incubation time 24 h, and 2.5 mM concentration of zinc sulfate (ZnSO4). The quadratic model predicted 1.3-fold increase anti-quorum sensing activity production over un-optimized cultural conditions. The present research is the first report representing the enhancement of anti-quorum sensing potential of L. rhamnosus GG. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03187-2.

17.
Future Microbiol ; 17: 773-787, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35450448

RESUMO

Aim: To study the influence of plant volatiles, bioactives and synthetic antibiotics on the attenuation of the quorum sensing (QS)-regulated virulence factors of Pseudomonas aeruginosa. Materials & methods: QS inhibition; the QS-regulated virulence factors pyocyanin, hemolysin, elastase, protease, alginate and pyochelin; and motility phenotypes were performed at sub-MIC to check the attenuation effect of 24 agents on the virulence of P. aeruginosa. Results: Eighteen out of 24 assayed compounds exhibited anti-QS activity and reduced the production of all virulence factors. Cinnamaldehyde, zingerone and lavender oil exhibited a significant reduction in motility phenotypes. Conclusion: Natural phytomolecules as a whole or their bioactives could be used to develop antivirulence drugs after in vivo evaluation.


Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Antibacterianos/farmacologia , Biofilmes , Fatores de Virulência/genética
18.
J Appl Microbiol ; 132(5): 3515-3532, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35064991

RESUMO

Unconstrained consumption of antibiotics throughout the expanse of the 21st century has resulted in increased antimicrobial resistance (AMR) among bacterial pathogens, a transpiring predicament affecting the public healthcare sector. The upsurge of multidrug-resistant pathogens, including Staphylococcus aureus, synchronously with the breakdown of the conventional antibiotic pipeline has led to the exploration of alternate strategies. Phage therapy applications have thus gained immense prominence among the scientific community to conquer this notorious pathogen associated with wide-ranging clinical manifestations, especially in immunosuppressed individuals. In this direction, a plethora of phage formulations like topical solutions, medicated dressings impregnated with phages, liposomal entrapments, etc., have been considered as an effective and upcoming strategy. Owing to the synergistic effect of phages with other antibacterial agents, they can be easily exploited for biomedical application. This review primarily focuses on the therapeutic implications of S. aureus phages in the biotechnological and medical arena. Through this review article, we have also discussed the current status and the incurring challenges in phage therapy.


Assuntos
Terapia por Fagos , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Infecções Estafilocócicas/microbiologia , Fagos de Staphylococcus/genética , Staphylococcus aureus
19.
Environ Microbiol ; 24(6): 2630-2656, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34559444

RESUMO

Pseudomonas aeruginosa is an opportunistic pathogen and the leading cause of mortality among immunocompromised patients in clinical setups. The hallmarks of virulence in P. aeruginosa encompass six biologically competent attributes that cumulatively drive disease progression in a multistep manner. These multifaceted hallmarks lay the principal foundation for rationalizing the complexities of pseudomonal infections. They include factors for host colonization and bacterial motility, biofilm formation, production of destructive enzymes, toxic secondary metabolites, iron-chelating siderophores and toxins. This arsenal of virulence hallmarks is fostered and stringently regulated by the bacterial signalling system called quorum sensing (QS). The central regulatory functions of QS in controlling the timely expression of these virulence hallmarks for adaptation and survival drive the disease outcome. This review describes the intricate mechanisms of QS in P. aeruginosa and its role in shaping bacterial responses, boosting bacterial fitness. We summarize the virulence hallmarks of P. aeruginosa, relating them with the QS circuitry in clinical infections. We also examine the role of QS in the development of drug resistance and propose a novel antivirulence therapy to combat P. aeruginosa infections. This can prove to be a next-generation therapy that may eventually become refractory to the use of conventional antimicrobial treatments.


Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes , Humanos , Pseudomonas aeruginosa/metabolismo , Virulência , Fatores de Virulência/metabolismo
20.
Microb Biotechnol ; 15(6): 1695-1718, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34843159

RESUMO

Unregulated consumption and overexploitation of antibiotics have paved the way for emergence of antibiotic-resistant strains and 'superbugs'. Pseudomonas aeruginosa is among the opportunistic nosocomial pathogens causing devastating infections in clinical set-ups globally. Its artillery equipped with diversified virulence elements, extensive antibiotic resistance and biofilms has made it a 'hard-to-treat' pathogen. The pathogenicity of P. aeruginosa is modulated by an intricate cell density-dependent mechanism called quorum sensing (QS). The virulence artillery of P. aeruginosa is firmly controlled by QS genes, and their expression drives the aggressiveness of the infection. Attempts to identify and develop novel antimicrobials have seen a sharp rise in the past decade. Among different proposed mechanisms, a novel anti-virulence approach to target pseudomonal infections by virtue of anti-QS and anti-biofilm drugs appears to occupy the centre stage. In this respect, bioactive phytochemicals have gained prominence among the scientific community owing to their significant quorum quenching (QQ) properties. Recent studies have shed light on the QQ activities of various phytochemicals and other drugs in perturbing the QS-dependent virulence in P. aeruginosa. This review highlights the recent evidences that reinforce the application of plant bioactives for combating pseudomonal infections, their advantages and shortcomings in anti-virulence therapy.


Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Antibacterianos/farmacologia , Biofilmes , Reposicionamento de Medicamentos , Compostos Fitoquímicos/farmacologia , Pseudomonas aeruginosa/metabolismo , Fatores de Virulência/genética
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