Suppression of virulence factors of <i>Pseudomonas aeruginosa</i> by erythromycin

Kita, Eisuke; Sawaki, Masayoshi; Oku, Daisuke; Hamuro, Akiko; Mikasa, Keiichi; Konishi, Mitsuru; Emoto, Masashi; Takeuchi, Shoji; Narita, Nobuhiro; Kashiba, Shuzo

doi:10.1093/jac/27.3.273

Cited by 76 publications

(47 citation statements)

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“…This was an unexpected finding, considering the high levels of resistance that P. aeruginosa shows toward these drugs, and general anti-inflammatory effects associated with macrolides were suggested to account for the positive results (312). However, in vitro testing with subinhibitory concentrations of macrolides indicated an additional effect of their application on reduction of P. aeruginosa virulence factor expression, including decreased production of exotoxin A, proteases, elastase, DNase, leukocidin, and phospholipase C (313)(314)(315). Positive outcomes from sub-MIC AZM treatments against P. aeruginosa in a murine pneumonia model provided further laboratory evidence that macrolides could affect the physiology of the bacteria without inhibiting their growth in vivo (316).…”

Section: Antibiotics As Qs Inhibitorsmentioning

confidence: 98%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

689

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: 98%

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

LaSarre

Federle

2013

Microbiol Mol Biol Rev

689

556

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“…However, preincubation of neutrophils alone with erythromycin was without effect, suggesting that erythromycin might reduce P. aeruginosa's production of factors that damage epithelia or stimulate neutrophilmediated cytotoxicity. At sub-MIC levels, macrolides inhibit the synthesis of exotoxin A, elastase, phospholipase C, DNase, lecithinase, gelatinase, lipase, and pyocyanin, all of which are virulence factors associated with P. aeruginosa infection (89,143,193,195,266). Tateda and coworkers (297) showed that a 48-hour exposure to macrolides at sub-MIC levels decreased the viability of both mucoid and nonmucoid P. aeruginosa strains.…”

Section: Inhibition Of Virulence Factorsmentioning

confidence: 99%

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010

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SUMMARY Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-κB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.

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“…It has recently been reported that treatment with erythromycin (EM) improves the clinical symptoms and prognosis of patients with chronic pulmonary infections (18). Kita et al (18) have shown that erythromycin stearate (EMS) suppresses the production of protease and leukocidin by P. aeruginosa without affecting cell growth and speculated that EMS may affect the virulence factors of this organism (18) and host defense mechanisms (7,9,17).…”

mentioning

confidence: 99%

Comparative in vitro exoenzyme-suppressing activities of azithromycin and other macrolide antibiotics against Pseudomonas aeruginosa

Mizukane

Hirakata

Kaku

et al. 1994

Antimicrob Agents Chemother

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The inhibitory effects of azithromycin (AZM), a new 15-membered macrolide antibiotic, on the production of exotoxin A, total protease, elastase, and phospholipase C by Pseudomonas aeruginosa were determined, and the virulence-suppressing effects of AZM were compared with those of erythromycin (EM), roxithromycin (RXM), and rokitamycin (RKM). The elfect of exposure ofP. aeruginosa PA103 or B16 in cultures to sub-MICs of these macrolide antibiotics on the production of exoenzymes was determined. AZM suppressed the in vitro production of extracellular and intracellular exotoxin A by P. aeruginosa PA103 more than did EM, even at a concentration of only 2 ,ug/ml. At concentrations of between 4 and 32 ,ug/ml, AZM also inhibited total protease, elastase, and phospholipase C production by P. aeruginosa B16 more than did EM, RXM, and RKM. AZM was effective in suppressing exotoxin A and total protease production through 24 h of incubation in the presence of drug at sub-MICs, but it had no significant effect on either the growth of P. aeruginosa or its total protein production. Moreover, at a concentration of 4 ,ug/ml, AZM suppressed exoenzyme production by other strains of P. aeruginosa more than did EM. These findings indicate that AZM, EM, RXM, and RKM each has an inhibitory effect on exoenzyme production separate from the antimicrobial effect and that, of these macrolides, AZM has the strongest virulence-suppressing effect.Pseudomonas aeruginosa is an opportunistic pathogen which frequently causes severe septicemia in immunocompromised hosts (4, 5). It is also the principal pulmonary pathogen in patients with cystic fibrosis (24, 33) and diffuse panbronchiolitis (16). P. aeruginosa exoenzymes, including exotoxin A, alkaline protease, elastase, and phospholipase C, are known to be virulence factors of importance in the various types of P. aeruginosa infections (26). The findings of our previous studies have suggested that P. aeruginosa isolates from blood cultures produce large quantities of exotoxin A and total protease (10) and that the production of exotoxin A plays an important role in the pathogenesis of endogenous P. aeruginosa septicemia in mice (13).It has recently been reported that treatment with erythromycin (EM) improves the clinical symptoms and prognosis of patients with chronic pulmonary infections (18). Kita et al. (18) have shown that erythromycin stearate (EMS) suppresses the production of protease and leukocidin by P. aeruginosa without affecting cell growth and speculated that EMS may affect the virulence factors of this organism (18) and host defense mechanisms (7, 9, 17). More recently, we have shown that erythromycin lactobionate (EML) suppresses the in vitro pro-

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Suppression of virulence factors of Pseudomonas aeruginosa by erythromycin

Cited by 76 publications

References 0 publications

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Comparative in vitro exoenzyme-suppressing activities of azithromycin and other macrolide antibiotics against Pseudomonas aeruginosa

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