Targeting virulence: A new paradigm for antifungals

Gauwerky, Katharina; Borelli, Claudia; Körting, Hans Christian

doi:10.1016/j.drudis.2008.11.013

Cited by 158 publications

(123 citation statements)

References 67 publications

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…Meanwhile, the availability of well-established pharmaceutics is greatly reduced due to the rapidly growing number of multidrugresistant strains. The current paradigm in the discovery of novel promising antimicrobial therapeutics postulates their targeting to microbial virulence factors/abilities rather than direct biocidal activity (Bink et al, 2011;Chevalier et al, 2012;Gauwerky et al, 2009;Naicker & Patel, 2013;Rajeshkumar & Sundararaman, 2012). The antifungal potential of tested SFs from plant extracts seems to fulfil these needs.…”

Section: Discussionmentioning

confidence: 99%

New pharmacological properties of Medicago sativa and Saponaria officinalis saponin-rich fractions addressed to Candida albicans

Sadowska

Budzyńska

Więckowska-Szakiel

et al. 2014

Journal of Medical Microbiology

View full text Add to dashboard Cite

The antifungal activity of the saponin-rich fractions (SFs) from Medicago sativa (aerial parts and roots) and Saponaria officinalis (used as a well-known source of plant saponins) against Candida albicans reference and clinical strains, their yeast-to-hyphal conversion, adhesion, and biofilm formation was investigated. Direct fungicidal/fungistatic properties of the tested phytochemicals used alone, as well as their synergy with azoles (probably resulting from yeast cell wall instability) were demonstrated. Here, to the best of our knowledge, we report for the first time the ability of saponin-rich extracts of M. sativa and S. officinalis to inhibit C. albicans germ tube formation, limit hyphal growth, reduce yeast adherence and biofilm formation, and eradicate mature (24 h) Candida biofilm. Moreover, M. sativa SFs (mainly obtained from aerial parts), in the range of concentrations which were active modulators of Candida virulence factors, exhibited low cytotoxicity against the mouse fibroblast line L929. These properties seem to be very promising in the context of using plant-derived SFs as potential novel antifungal therapeutics supporting classic drugs or as ingredients of disinfectants. INTRODUCTIONCandida albicans is probably the best known and at the same time the most effective opportunistic fungal pathogen of humans and animals. It constitutes a commensal microflora in the gastrointestinal and genitourinary tracts of .70 % of humans. However, in certain circumstances C. albicans could be pathogenic to critically ill, immunocompromised patients or even to healthy persons. It causes a diverse range of pathologies -from local cutaneous and mucosal infections (e.g. candidiasis of nail shafts and nails, oropharyngeal candidiasis, intestinal candidiasis) to lifethreatening systemic infections, such as candidaemia, fungal pneumonia, meningitidis or endocarditis (Cannon et al., 2009;Kabir et al., 2012;Kabir & Ahmad, 2013;Sardi et al., 2013; Tlamçani & Er-rami, 2013). Endogenous candidaemia and the carrier state are the main mechanisms of Candida spp. spread and transmission, although exogenous infections are also possible (Mathé & van Dijck, 2013;Sardi et al., 2013). The pathogenicity and high invasiveness of C. albicans arise from the broad range of its virulence factors. These include tissue-damaging hydrolytic enzymes: proteases (mainly secreted aspartic proteinases), phospholipases and haemolysins, but first of all the agents/abilities contributing to its strong adherence (e.g. two main C. albicans adhesions: agglutinin-like sequence and hyphal wall protein-1), biofilm formation and the transformation of morphological forms (yeast-to-hyphal). Also, the ability of C. albicans to survive in various anatomical body sites and to evade host defences seems to be essential (Chai et al., 2009;Chandra et al., 2001;Gropp et al., 2009;Sardi et al., 2013).Invasive candidiasis usually results from tissue colonization by yeast and formation of biofilm -the structured multicellular microbial communities embedded in a self-...

show abstract

Section: Discussionmentioning

confidence: 99%

New pharmacological properties of Medicago sativa and Saponaria officinalis saponin-rich fractions addressed to Candida albicans

Sadowska

Budzyńska

Więckowska-Szakiel

et al. 2014

Journal of Medical Microbiology

View full text Add to dashboard Cite

show abstract

“…More recently, specifically targeting virulence rather than essential fungal processes has been discussed as a 'new' paradigm for the development of antibacterial and antifungal agents [74,75]. The modulation of morphogenesis may provide a way to specifically target virulence of C. albicans [76].…”

Section: Is Inhibition Of the Yeast-to-hyphal Transition A Therapeutimentioning

confidence: 99%

Candida albicansdimorphism as a therapeutic target

Jacobsen

Wilson

Wachtler

et al. 2012

Expert Review of Anti-infective Therapy

314

247

View full text Add to dashboard Cite

“…The researchers thus face a major challenge to develop new, safe and more effective antifungals taking into account the increase in opportunistic infections in the immune compromised host. This can be overcome by the discovery of new drugs acting by novel mechanisms of action [16][17][18].…”

Section: Fungal Infection Prominent In Particular Diseasesmentioning

confidence: 99%

Antimicrobial Agents

Asif¹

2017

JAPLR

View full text Add to dashboard Cite

Submit Manuscript | http://medcraveonline.com IntroductionUse of substances with antimicrobial properties is known to have been common practice for at least 2000 years. Ancient Egyptians and ancient Greeks used specific molds and plant extracts to treat infection. More recently, microbiologists such as Louis Pasteur and Jules Francois Joubert observed antagonism for some bacteria and discussed the merits of controlling these interactions in medicine. In 1928, Alexander Fleming became the first to discover a natural powerful antimicrobial fungus known as Penicillium Rubens. The substance extracted from the fungus he named Penicillin and in 1942 it was successfully used to treat a Streptococcus infections [1,2]. But nowadays, all over the world treatment of using antimicrobial agents is currently facing its own limitation, due to the development of resistance by the microbes over the period of time. Bacteria are involved in many aspects of ecology and health. It seems likely that all species both benefit and suffer from interactions with bacteria. For example we use bacteria for making yoghurt, curd, cheese and other fermented foods and also large number of bacteria lives on the skin and in the digestive tract. The human gut contains more than 1000 bacterial species which are beneficial [3]. Gut bacteria synthesize vitamins such as Folic Acid, Vitamin K and biotin and they ferment the complex, indigestible carbohydrates. Other useful bacteria in the gut flora include Lactobacillus species, which convert milk sugar into Lactic Acid. Also bacteria play very important role in the medicine such as vaccine component and in the production of antibiotics, drugs, hormones, and antibodies. On the other hand a pathogenic bacterium causes an enormous level of spoilage, suffering and death through the infection. The bacterial cells differs dramatically in structure and function compared to mammalian cells. The bacterial cytoplasm is separated from the external environment by a cytoplasmic membrane, as shown in Figure 1. The bacterial cell wall is chemically distinct from mammalian cell [4] walls and so is constructed by enzymes that often have no direct counterpart in mammalian cell construction. The following are the functions of the various parts of the bacterial cell. Cell WallProtects the cell and maintains its shape, bacteria can be categorized according to their cell wall type: Some bacteria have a slimy layer of polysaccharides and polypeptides, allowing them to attach to objects and providing protection. 70s ribosomesThese are for performing protein synthesis. They are smaller than the 80s ribosomes in eukaryotic cells. Flagellum another optional feature is a projection that moves around to allow the cell to move. A cell may have multiple flagella arranged around it. AbstractThe word antimicrobial was derived from the Greek words anti (against), micro (little) and bios (life) and refers to all agents that act against microbial organisms. Antimicrobial agent is a general term that is mainly concerned with antibiotics...

show abstract

Targeting virulence: A new paradigm for antifungals

Cited by 158 publications

References 67 publications

New pharmacological properties of Medicago sativa and Saponaria officinalis saponin-rich fractions addressed to Candida albicans

New pharmacological properties of Medicago sativa and Saponaria officinalis saponin-rich fractions addressed to Candida albicans

Candida albicansdimorphism as a therapeutic target

Antimicrobial Agents

Contact Info

Product

Resources

About