Quorum Sensing Inhibitors as Pathoblockers for Pseudomonas aeruginosa Infections: A New Concept in Anti-Infective Drug Discovery

Kamal, Ahmed A. M.; Maurer, Christine K.; Allegretta, Giuseppe; Haupenthal, Jörg; Empting, Martin; Hartmann, Rolf W.

doi:10.1007/7355_2017_17

Cited by 16 publications

(17 citation statements)

References 93 publications

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“…In contrast to the conventional microbicidal antibiotics, antivirulence agents curb the pathogenicity/virulence without necessarily displaying any notable growth-inhibitory effect. Such “pathoblockers” are likely to emerge as a new category of “tailored spectrum” superior therapeutics [39–41]. Based on this logic and early enthusiasm surrounding QS inhibitors, latter were viewed as “evolution-proof drugs” [42].…”

Section: Discussionmentioning

confidence: 99%

Antipathogenic Potential of a Polyherbal Wound-Care Formulation (Herboheal) against Certain Wound-Infective Gram-Negative Bacteria

Patel

Joshi

Kothari

2019

Advances in Pharmacological Sciences

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This study investigated antipathogenic efficacy of a polyherbal wound-healing formulation Herboheal against three multidrug-resistant strains of gram-negative bacterial pathogens associated with wound infections. Herboheal was evaluated for its quorum-modulatory potential against three different human-pathogenic bacteria, first in vitro through the broth dilution assay and then in vivo in the model host Caenorhabditis elegans. Herboheal at ≥0.1% v/v was able to inhibit (19–55%) in vitro production of quorum sensing-regulated pigments in all these bacteria and seemed to interfere with bacterial quorum sensing by acting as a signal-response inhibitor. This formulation could compromise haemolytic activity of all three bacteria by ∼18–69% and induced their catalase activity by ∼8–21%. Herboheal inhibited P. aeruginosa biofilm formation up to 40%, reduced surface hydrophobicity of P. aeruginosa cells by ∼9%, and also made them (25%) more susceptible to lysis by human serum. Antibiotic susceptibility of all three bacteria was modulated owing to pretreatment with Herboheal. Exposure of these test pathogens to Herboheal (≥0.025% v/v) effectively reduced their virulence towards the nematode Caenorhabditis elegans. Repeated subculturing of P. aeruginosa on the Herboheal-supplemented growth medium did not induce resistance to Herboheal in this mischievous pathogen, and this polyherbal extract was also found to exert a post-extract effect on P. aeruginosa, wherein virulence of the Herboheal-unexposed daughter cultures, of the Herboheal-exposed parent culture, was also found to be attenuated. Overall, this study indicates Herboheal formulation to be an effective antipathogenic preparation and validates its indicated traditional therapeutic use as a wound-care formulation.

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Section: Discussionmentioning

confidence: 99%

Antipathogenic Potential of a Polyherbal Wound-Care Formulation (Herboheal) against Certain Wound-Infective Gram-Negative Bacteria

Patel

Joshi

Kothari

2019

Advances in Pharmacological Sciences

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“…Carbapenem-resistant Pseudomonas aeruginosa is one of the most critical antibiotic-resistant bacteria as recently classified by the World Health Organization 1 , which is the reason why current anti-infective research is dedicated to the development of new treatment options against this pathogen 2 , 3 . Infections with P. aeruginosa lead to severe complications in chronic lung diseases like cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and non-CF bronchiectasis (NCFB), often leading to significantly increased morbidity and mortality 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

Micro-rheological properties of lung homogenates correlate with infection severity in a mouse model of Pseudomonas aeruginosa lung infection

Murgia

Kany

Herr

et al. 2020

Sci Rep

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Lung infections caused by Pseudomonas aeruginosa pose a serious threat to patients suffering from, among others, cystic fibrosis, chronic obstructive pulmonary disease, or bronchiectasis, often leading to life-threatening complications. The establishment of a chronic infection is substantially related to communication between bacteria via quorum-sensing networks. In this study, we aimed to assess the role of quorum-sensing signaling molecules of the Pseudomonas quinolone signal (PQS) and to investigate the viscoelastic properties of lung tissue homogenates of PA-infected mice in a prolonged acute murine infection model. Therefore, a murine infection model was successfully established via intra-tracheal infection with alginate-supplemented Pseudomonas aeruginosa NH57388A. Rheological properties of lung homogenates were analyzed with multiple particle tracking (MPT) and quorum-sensing molecules were quantified with LC–MS/MS. Statistical analysis of bacterial load and quorum-sensing molecules showed a strong correlation between these biomarkers in infected lungs. This was accompanied by noticeable changes in the consistency of lung homogenates with increasing infection severity. Furthermore, viscoelastic properties of the lung homogenates strongly correlated with bacterial load and quorum sensing molecules. Considering the strong correlation between the viscoelasticity of lung homogenates and the aforementioned biomarkers, the viscoelastic properties of infected lungs might serve as reliable new biomarker for the evaluation of the severity of P. aeruginosa infections in murine models.

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“…Ability of GLE to interfere with bacterial QS is an important observation, as QS in recent years has emerged as a potential target for novel anti-pathogenic agents ( Fong et al , 2018). These ‘pathoblockers’ may attenuate virulence of the target pathogens without necessarily killing them ( Kamal et al , 2017).…”

Section: Resultsmentioning

confidence: 99%

Anti-infective efficacy of Psidium guajava L. leaves against certain pathogenic bacteria

et al. 2019

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Water extracts of Psidium guajava leaves prepared by three different extraction methods were compared with respect to their anti-infective activity against Pseudomonas aeruginosa and Staphylococcus aureus in the nematode host Caenorhabditis elegans. The water extract prepared by Microwave Assisted Extraction method was found to have better anti-infective activity, and its activity was further compared with hydroalcoholic extract prepared using the same extraction method against five different pathogenic bacteria. Both these extracts could attenuate virulence of P. aeruginosa, S. aureus, Serratia marcescens, and Chromobacterium violaceum, towards C. elegans. Anti-infective efficacy of P. guajava leaf extract seems partly to stem from its quorum-modulatory property, as it could modulate production of quorum sensing-regulated pigments in all the susceptible bacteria.

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Quorum Sensing Inhibitors as Pathoblockers for Pseudomonas aeruginosa Infections: A New Concept in Anti-Infective Drug Discovery

Cited by 16 publications

References 93 publications

Antipathogenic Potential of a Polyherbal Wound-Care Formulation (Herboheal) against Certain Wound-Infective Gram-Negative Bacteria

Antipathogenic Potential of a Polyherbal Wound-Care Formulation (Herboheal) against Certain Wound-Infective Gram-Negative Bacteria

Micro-rheological properties of lung homogenates correlate with infection severity in a mouse model of Pseudomonas aeruginosa lung infection

Anti-infective efficacy of Psidium guajava L. leaves against certain pathogenic bacteria

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