Subinhibitory concentrations of nalidixic acid alter bacterial physiology and induce anthropogenic resistance in a commensal strain of
            <i>Escherichia coli in vitro</i>

Chadha, Jatin; Khullar, Lavanya

doi:10.1111/lam.13550

Cited by 18 publications

(9 citation statements)

References 46 publications

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“…Hence, a biofilm with sessile and adherent cells encapsulated in extracellular polymeric substances (EPS) comes to the rescue. Other factors like nutrient starvation, signalling by secondary messengers and sub-inhibitory concentration of antibiotics may also induce biofilm formation (Chadha, 2021;Chadha and Khullar, 2021). These microbial scaffolds have been shown to confer resistance against phagocytosis, oxidative stress, nutrient depletion, interspecies competition, antimicrobial drugs and antibiotics in P. aeruginosa (Olsen, 2015).…”

Section: Invasins: Knocking the Keep For A Cellular Conquestmentioning

confidence: 99%

Revisiting the virulence hallmarks of Pseudomonas aeruginosa: a chronicle through the perspective of quorum sensing

Chadha

Harjai

Chhibber

2021

Environmental Microbiology

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106

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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.

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Section: Invasins: Knocking the Keep For A Cellular Conquestmentioning

confidence: 99%

Revisiting the virulence hallmarks of Pseudomonas aeruginosa: a chronicle through the perspective of quorum sensing

Chadha

Harjai

Chhibber

2021

Environmental Microbiology

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105

106

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“…Indiscriminate use and unregulated consumption of antibiotics have paved the way for the emergence of multidrug-resistant (MDR) bacterial pathogens worldwide ( Chadha and Khullar, 2021 ). Among the challenging ESKAPE pathogens, Pseudomonas aeruginosa has emerged as an extraordinarily versatile and notorious pathogen associated with a wide range of nosocomial infections in immunocompromised patients with relatively high mortality rates ( Kang et al., 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection

Chadha

Ravi

Singh

et al. 2022

Front. Cell. Infect. Microbiol.

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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.

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“…At the dawn of this century, the excessive consumption and imprudent usage of antibiotics led to the emergence of multidrug resistance across human pathogens (Chadha, 2021; Chadha and Khullar, 2021). This has resulted in poor treatment outcomes and quality of patient life, thus raising huge concerns among clinicians and microbiologists.…”

Section: Introductionmentioning

confidence: 99%

Exploring the therapeutic potential of staphylococcal phage formulations: Current challenges and applications in phage therapy

Khullar

Harjai

Chhibber

2022

Journal of Applied Microbiology

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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.

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Subinhibitory concentrations of nalidixic acid alter bacterial physiology and induce anthropogenic resistance in a commensal strain of Escherichia coli in vitro

Cited by 18 publications

References 46 publications

Revisiting the virulence hallmarks of Pseudomonas aeruginosa: a chronicle through the perspective of quorum sensing

Revisiting the virulence hallmarks of Pseudomonas aeruginosa: a chronicle through the perspective of quorum sensing

Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection

Exploring the therapeutic potential of staphylococcal phage formulations: Current challenges and applications in phage therapy

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