Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

Abstract

The airways of patients with bronchiectasis and cystic fibrosis are often chronically colonised by Pseudomonas aeruginosa (PA), which is virtually impossible to eradicate. Low-dose erythromycin (EM), for unknown mechanisms, is efficacious in bronchiectasis and diffuse panbronchiolitis.In this study, an in vitro model to investigate PA adherence to human type IV basement collagen was developed by using scanning electron microscopy (SEM). There were significantly less PA bacilli per 20 random SEM fields (4,0006) when PA was cultured in 0.05, 0.5 and 5 mg?mL -1 of EM compared with control (absence of EM). Adherence density (20 SEM fields?log -1 inocular size) for PA obtained from no EM (56.8¡43.16) was significantly higher than that obtained from 0.05, 0.5, and 5 mg?mL -1 EM (21.5¡17.56, 23.3¡16.65, and 21.4¡12.65 respectively). By using SEM it was found that PA, when incubated in EM (0.05, 0.5, 5 mg?mL -1 ) had a significant reduction in its diagonal length, radius, height, volume and surface area.It is possible, therefore, that these misshaped Pseudomonas aeruginosa bacilli are more susceptible to host defence mechanisms, while at the same time less adherent to the basement membrane of the airway in vivo. Therefore, this could help explain the clinical efficacy of low-dose erythromycin therapy on patients with Pseudomonas aeruginosa infection. Eur Respir J 2003; 21: 401-406.

Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action

“…Decreases in cell size (both rod diameter and length) have been detected in Legionella pneumophila treated with the peptidoglycan synthesis inhibitor ampicillin [141], and P. aeruginosa treated with the protein synthesis inhibitor erythromycin [167]. The cause(s) of these decreases in size was not established [141,167]. Lastly, a combination of both increased and decreased cell size has been observed in Staphylococcus aureus populations treated with novobiocin [168].…”

“…If, however, the enlarged bacteria are examined in cross-section, the increase in size can usually be attributed to inhibition of cell separation ('pseudomulticellular bacteria') [127,158], or osmotic swelling ('spheroplasts' or 'protoplasts') [84]. Decreases in cell size (both rod diameter and length) have been detected in Legionella pneumophila treated with the peptidoglycan synthesis inhibitor ampicillin [141], and P. aeruginosa treated with the protein synthesis inhibitor erythromycin [167]. The cause(s) of these decreases in size was not established [141,167].…”

Pseudomonas aeruginosaadherence to human basement membrane collagenin vitro

“…Adherence to basement membrane is, therefore, an important issue that has not been studied previously. Therefore, the authors have recently established a model to study bacterial adherence to basement membrane collagen and applied this to evaluate the effects of various chemicals on the adherence of P. aeruginosa to collagen in vitro [10].…”

An investigation into the effect of erythromycin on Pseudomonas aeruginosa quorum sensing in non-cystic fibrosis bronchiectasis

“…aeruginosa are well described [117] with inhibitory effects on flagellin expression, exoenzyme production [118] and collagen adherence [119]. Multiple studies have demonstrated that macrolide antibiotics interfere with the quorum sensing circuitry of P. aeruginosa in vitro [20,21,43,74,117,119,120] [ 17,20,[120][121][122][123].…”

“…Multiple studies have demonstrated that macrolide antibiotics interfere with the quorum sensing circuitry of P. aeruginosa in vitro [20,21,43,74,117,119,120] [ 17,20,[120][121][122][123]. Macrolide antibiotics have been shown to inhibit the expression of rhlAB (rhamnolipid), lasR, rhlR, lasI and rhlI [21] as well as the production of elastase, pyocyanin [120]) and quorum sensing molecules [20,21].…”