Use of locally delivered dequalinium chloride in the treatment of vaginal infections: a review

Mendling, Werner; Weissenbacher, E. R.; Gerber, Stefan; Prasauskas, Valdas; Grob, P.

doi:10.1007/s00404-015-3914-8

Cited by 71 publications

(79 citation statements)

References 78 publications

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“…Such result is also clinically relevant since these drugs could have a harmful effect in certain patients. We further validate such negative effect for Dequalinium (DQ), a cytotoxic drug used as antiseptic and disinfectant (43). DQ and its derivates has been studied for the treatment of distinct cancer types (44,45), the use of nanosomes to induce apoptosis by production of ROS (46), and the mitochondrial targeting in nanomedicine (47).…”

Section: Discussionmentioning

confidence: 71%

Splicing-related Retinitis Pigmentosa mutations mimicked in C. elegans allow the identification of disease modifiers and drug screens

Kukhtar

Rubio-Peña

Serrat

et al. 2019

Preprint

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CRISPR and the high conservation of the spliceosome components facilitate the mimicking of human pathological mutations in splicing factors of model organisms. The degenerative retinal disease Retinitis Pigmentosa (RP) is caused by mutations in distinct types of genes, including missense mutations in splicing factors that provoke RP in an autosomal dominant form (s-adRP). Using CRISPR in C. elegans, we generated mutant strains to mimic RP mutations reported in PRPF8 and SNRNP200. Whereas these inherited mutations are present in heterozygosis in patients, C. elegans allows the maintenance of these mutations in homozygosis, which is advantageous for genetic and drug screens. We found that snrp-200(cer23[V676L]) and prp-8(cer14 [H2302del]) display pleiotropic phenotypes, including a reduced fertility.However, snrp-200(cer24[S1080L]) and prp-8(cer22[R2303G]) are weak alleles suitable for RNAi screens to identify genetic interactions, which would uncover potential disease modifiers. We screened a collection of RNAi clones for splicing-related genes and identified three splicing factors, isy-1/ISY1, cyn-15/PPWD1 and mog-2/SNRPA1 whose partial inactivation may modify the course of the disease. Interestingly, these three genes were acting as modifiers of prp-8(cer22) but no snrp-200(cer24).Finally, the strong allele prp-8(cer14) was used in a screen with FDA-approved drugs to find molecules capable of alleviating the phenotype. Instead, we detected drugs, as Dequalinium Chloride, which exacerbated the phenotype and therefore are potentially harmful for s-adRP patients since they may accelerate the progression of the disease.

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Section: Discussionmentioning

confidence: 71%

Splicing-related Retinitis Pigmentosa mutations mimicked in C. elegans allow the identification of disease modifiers and drug screens

Kukhtar

Rubio-Peña

Serrat

et al. 2019

Preprint

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“…This finding supports the potential relationship between antibiotics and disinfectants resistance, as well as the possible induction of AR by disinfectants of common use. In particular, the induction of mexCD-oprJ by dequalinium chloride could have clinical relevance, as this compound forms part of several antiseptic and disinfection procedures (50) and its use has been considered for the treatment for promyelocytic leukemia (51–54).…”

Section: Resultsmentioning

confidence: 99%

Novel inducers of the expression of multidrug efflux pumps that triggerPseudomonas aeruginosatransient antibiotic resistance

Laborda

Alcalde-Rico

Blanco

et al. 2019

Preprint

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The study of the acquisition of antibiotic resistance (AR) has mainly focused in inherited processes, namely mutations and acquisition of AR genes. However, inducible, non-inheritable AR has received less attention and most information in this field derives from the study of antibiotics as inducers of their associated resistance mechanisms. Less is known about non-antibiotic compounds or situations that can induce AR during infection. Multidrug resistance efflux pumps are a category of AR determinants characterized by the tightly regulation of their expression. Their contribution to acquired AR relies in their overexpression. Herein we analyzed potential inducers of the expression of the chromosomally-encoded Pseudomonas aeruginosa clinically-relevant efflux pumps, MexCD-OprJ and MexAB-OprM. For this purpose, we developed a set of luxCDABE-based P. aeruginosa biosensor strains, which allows the high-throughput analysis of compounds able of modifying the expression of these efflux pumps. Using these strains, we analyzed a set of 240 compounds present in Biolog Phenotype Microarrays. Several inducers of the expression of the genes that encode these efflux pumps were found. The study focused in dequalinium chloride, procaine and atropine, compounds that can be found in clinical settings. Using real-time PCR, we confirmed that these compounds indeed induce the expression of mexCD-oprJ. In addition, P. aeruginosa presents lower susceptibility to ciprofloxacin (a MexCD-OprJ substrate) when dequalinium chloride, procaine or atropine are present. This work emphasizes the need of studying compounds that can trigger transient AR during antibiotic treatment, a phenotype difficult to discover using classical susceptibility tests.

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“…DNA as a Component of G. vaginalis Biofilms BV can be treated with antibiotics (most often metronidazole and clindamycin) and antiseptics (e.g., dequalinium chloride) (Mendling et al, 2016). However, though initially effective in ∼80% of cases, the rates of recurrence following antibiotic treatment are extremely high; >50% of women will have recurrent episode(s) within 6-12 months (Bradshaw and Brotman, 2015).…”

Section: Experimental Studies In Vivo Using Gardnerella Alone Vaginalmentioning

confidence: 99%

Gardnerella vaginalis as a Cause of Bacterial Vaginosis: Appraisal of the Evidence From in vivo Models

Morrill

Gilbert

Lewis

2020

Front. Cell. Infect. Microbiol.

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Koch's postulates dictate the use of experimental models to illustrate features of human disease and provide evidence for a singular organism as the cause. The underlying cause(s) of bacterial vaginosis (BV) has been debated in the literature for over half a century. In 1955, it was first reported that a bacterium now known as Gardnerella vaginalis may be the cause of a condition (BV) resulting in higher vaginal pH, thin discharge, a fishy odor, and the presence of epithelial cells covered in bacteria. Here we review contemporary and historical studies on BV with a focus on reports of experimental infections in human or animal models using Gardnerella vaginalis. We evaluate experimental evidence for the hypothesis that G. vaginalis is sufficient to trigger clinical features of BV or relevant health complications associated with the condition. Additionally, we evaluate in vivo models of co-infection employing G. vaginalis together with other bacterial species to investigate evidence for the hypothesis that G. vaginalis may encourage colonization or virulence of other potential pathogens. Together, these studies paint a complex picture in which G. vaginalis has both direct and indirect roles in the features, health complications, and co-infections associated with BV. We briefly review the current taxonomic landscape and genetic diversity pertinent to Gardnerella and note the limitations of sequence-based studies using different marker genes and priming sites. Although much more study is needed to refine our understanding of how BV develops and persists within the human host, applications of the experimental aspects of Koch's postulates have provided an important glimpse into some of the causal relationships that may govern this condition in vivo.

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Use of locally delivered dequalinium chloride in the treatment of vaginal infections: a review

Cited by 71 publications

References 78 publications

Splicing-related Retinitis Pigmentosa mutations mimicked in C. elegans allow the identification of disease modifiers and drug screens

Splicing-related Retinitis Pigmentosa mutations mimicked in C. elegans allow the identification of disease modifiers and drug screens

Novel inducers of the expression of multidrug efflux pumps that triggerPseudomonas aeruginosatransient antibiotic resistance

Gardnerella vaginalis as a Cause of Bacterial Vaginosis: Appraisal of the Evidence From in vivo Models

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