Azithromycin Inhibits Quorum Sensing in
            <i>Pseudomonas aeruginosa</i>

Tateda, Kazuhiro; Comte, Rachel; Péchère, Jean-Claude; Köhler, Thilo; Yamaguchi, Keizo; Delden, Christian van

doi:10.1128/aac.45.6.1930-1933.2001

Cited by 372 publications

(293 citation statements)

References 30 publications

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“…These reductions coincided with reduced Las-and Rhl-dependent gene transcription and have been corroborated by microarray and proteomic studies (319,320), which found, in addition to QS gene misregulation, a reduction in levels of oxidative stress and motility-related genes but an increase in type III secretion (TTS)-related genes. The diminished response to oxidative stress conditions may account for the reduced cell viability in late stationary phase that was reported to occur with increasing concentrations of macrolides (318,319). Likewise, the finding that TTS was induced with exposure to AZM may explain the paradoxical finding that pretreatment of bacterial cultures with macrolides prior to intranasal inoculation in mice led to an enhanced lethal effect (321).…”

Section: Antibiotics As Qs Inhibitorsmentioning

confidence: 49%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

676

556

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SUMMARY Cell-cell communication, or quorum sensing, is a widespread phenomenon in bacteria that is used to coordinate gene expression among local populations. Its use by bacterial pathogens to regulate genes that promote invasion, defense, and spread has been particularly well documented. With the ongoing emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies. An antivirulence approach by which quorum sensing is impeded has caught on as a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity. The identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are reviewed here. Overall, the evidence suggests that QSI therapy may be efficacious against some, but not necessarily all, bacterial pathogens, and several failures and ongoing concerns that may steer future studies in productive directions are discussed. Nevertheless, various QSI successes have rightfully perpetuated excitement surrounding new potential therapies, and this review highlights promising QSI leads in disrupting pathogenesis in both plants and animals.

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Section: Antibiotics As Qs Inhibitorsmentioning

confidence: 49%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

676

556

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“…Macrolide antibiotics have been shown to act as QS inhibitors at subinhibitory concentrations. For example, erythromycin has been reported to suppress production of P. aeruginosa hemagglutinins, protease, hemolysin and AHL signals [14], and studies have shown that azithromycin at sub-MIC concentrations affects QS-regulated virulence genes and biofilm formation in vitro [15][16][17] and in in vivo models of disease [18]. In the present study, we demonstrate that sub-inhibitory concentrations of azithromycin could dose-dependently reduce the haemolytic activity and biofilm formation in S. aureus.…”

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confidence: 55%

Azithromycin Reduces the Production of α-hemolysin and Biofilm Formation in Staphylococcus aureus

et al. 2013

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Staphylococcus aureus causes a broad range of life-threatening diseases in humans. This bacterium produces a large number of extracellular virulence factors that are closely associated with specific diseases which are controlled by quorum sensing. In this study, we show that azithromycin was active against methicillin-resistant Staphylococcus aureus (MRSA) strains with MICs ranged from 32 to 64 lg/mL. Azithromycin at subinhibitory concentration, markedly reduced the production of a-hemolysin at (1/16MIC, 1/8MIC) and biofilm formation at (1/16MIC, 1/8MIC), respectively. The results indicated that sub-inhibitory concentrations of azithromycin decreased the production of a-hemolysin and biofilm formation in MRSA in a dose-dependent manner. Therefore, azithromycin may be useful in the treatment of a-hemolysin producing and biofilm formation MRSA infections.Staphylococcus aureus is found among the normal human skin flora and it is an important pathogen of humans, causing diseases ranging from superficial skin and wound infections to severe illnesses such as septicaemia, endocarditis and toxic shock syndrome [1]. S. aureus is particularly a problem in hospitals because it spreads easily in these environments and causes potentially fatal infections in immunocompromised hospital patients. S. aureus cause disease through the production of virulence factors. These factors include adhesins, exotoxins, enterotoxins, hemolysins, and leukocidin, as well as proteases that enable the bacteria to spread within the host [2,3]. Quorum sensing (QS) regulates expression of genes encoding these virulence factors and biofilm formation. Strains defective in their ability to form a biofilm or produce toxins show diminished virulence [4], suggesting that a novel approach for therapy development would be to interfere with the production of virulence factors [5][6][7]. Azithromycin (AZM) is one of the macrolides antibiotics, and it is a broad-spectrum macrolide antibiotic effective against Gram-positive, Gram-negative, and atypical bacteria and has anti-inflammatory characteristics [8]. The purpose of this study is to assess the effect of azithromycin, used as a quorum-sensing inhibitor, for decrease the production of QS associated virulence factors and biofilm formation in Staphylococcus aureus.Two different clinical bacterial strains of methicillinresistant Staphylococcus aureus (MRSA) 10 and 21 were collected from different patients hospitalized at Lishui People's Hospital, Zhejiang province. S. aureus strains was identified biochemically from routinely obtained specimens by means of the Vitek ATB Expression System, version 2.7.8 (BioMe'rieux Deutschland GmbH, Nürtin-gen, Germany), which uses 32 biochemical reactions. Bacterial isolates were stored as suspensions in LB medium containing 12.5 % (vol/vol) glycerol at -70°C until tests were performed. S. aureus MRSA 10, 21 single colony was inoculated into LB media and cultured overnight at 37. Overnight culture was subcultured (1:100) into test tubes with fresh LB medium in tripl...

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“…In a recent study, a screening of quorum-sensing-inhibiting molecules derived from the plant species Combretum albiflorum revealed that catechin has a negative impact on the production of quorumsensing-dependent virulence factors (Vandeputte et al, 2010). Subinhibitory concentrations of macrolides have been shown to be effective in inhibiting quorum-sensingdependent virulence both in vivo and in vitro (Imamura et al, 2004;Molinari et al, 1993;Sofer et al, 1999;Tateda et al, 2001). Furthermore, CF patients showed significant improvement in pulmonary function with the use of macrolides without any effect on the total Pseudomonas population (Fujii et al, 1995;Saiman et al, 2003).…”

Section: C M Antunes and Othersmentioning

confidence: 99%

Quorum sensing in bacterial virulence

et al. 2010

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Bacteria communicate through the production of diffusible signal molecules termed autoinducers. The molecules are produced at basal levels and accumulate during growth. Once a critical concentration has been reached, autoinducers can activate or repress a number of target genes. Because the control of gene expression by autoinducers is cell-density-dependent, this phenomenon has been called quorum sensing. Quorum sensing controls virulence gene expression in numerous micro-organisms. In some cases, this phenomenon has proven relevant for bacterial virulence in vivo. In this article, we provide a few examples to illustrate how quorum sensing can act to control bacterial virulence in a multitude of ways. Several classes of autoinducers have been described to date and we present examples of how each of the major types of autoinducer can be involved in bacterial virulence. As quorum sensing controls virulence, it has been considered an attractive target for the development of new therapeutic strategies. We discuss some of the new strategies to combat bacterial virulence based on the inhibition of bacterial quorum sensing systems.

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Azithromycin Inhibits Quorum Sensing in Pseudomonas aeruginosa

Cited by 372 publications

References 30 publications

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Azithromycin Reduces the Production of α-hemolysin and Biofilm Formation in Staphylococcus aureus

Quorum sensing in bacterial virulence

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