Rhamnolipids: diversity of structures, microbial origins and roles

Rhamnolipids are glycolipidic biosurfactants produced by various bacterial species. They were initially found as exoproducts of the opportunistic pathogen Pseudomonas aeruginosa and described as a mixture of four congeners: α-L-rhamnopyranosyl-α-L-rhamnopyranosyl-β-hydroxydecanoyl-β-hydroxydecanoate (Rha-Rha-C10-C10), α-L-rhamnopyranosyl-α-L-rhamnopyranosyl-β-hydroxydecanoate (Rha-Rha-C10), as well as their mono-rhamnolipid congeners Rha-C10-C10 and Rha-C10. The development of more sensitive analytical techniques has lead to the further discovery of a wide diversity of rhamnolipid congeners and homologues (about 60) that are produced at different concentrations by various Pseudomonas species and by bacteria belonging to other families, classes, or even phyla. For example, various Burkholderia species have been shown to produce rhamnolipids that have longer alkyl chains than those produced by P. aeruginosa. In P. aeruginosa, three genes, carried on two distinct operons, code for the enzymes responsible for the final steps of rhamnolipid synthesis: one operon carries the rhlAB genes and the other rhlC. Genes highly similar to rhlA, rhlB, and rhlC have also been found in various Burkholderia species but grouped within one putative operon, and they have been shown to be required for rhamnolipid production as well. The exact physiological function of these secondary metabolites is still unclear. Most identified activities are derived from the surface activity, wetting ability, detergency, and other amphipathic-related properties of these molecules. Indeed, rhamnolipids promote the uptake and biodegradation of poorly soluble substrates, act as immune modulators and virulence factors, have antimicrobial activities, and are involved in surface motility and in bacterial biofilm development

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin.

1. Patients with airway infection by Pseudomonas aeruginosa have impaired mucociliary clearance. Pyocyanin is a phenazine pigment produced by P. aeruginosa which is present in the sputum of colonized patients, slows human ciliary beat frequency (CBF) in vitro and slows mucociliary transport in vivo in the guinea-pig. 2. We have investigated the effect of salmeterol, a long-acting beta 2-adrenoceptor agonist, on pyocyanin-induced slowing of human CBF in vitro. Salmeterol (2 x 10(-7) M) was found to reduce pyocycanin (20 micrograms ml-1)-induced slowing of CBF by 53% and the fall in intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) by 26% and ATP by 29%. 3. Another beta 2-adrenoceptor agonist, isoprenaline (2 x 10(-7) M), also inhibited pyocyanin-induced slowing of CBF by 39%. 4. The effects of salmeterol (30 min preincubation) persisted after washing the cells. 5. Propranolol (10(-7) M) and the beta 2-specific antagonist, ICI 118551 (10(-6) M) blocked the protective effects of salmeterol completely, but atenolol (10(-6) M) was less effective. These results suggested that the effects of salmeterol on pyocyanin-induced effects were mediated primarily via the stimulation of beta 2-adrenoceptors. 6. Pyocyanin-induced ciliary slowing is associated with a substantial fall in intracellular cyclic AMP and ATP. Salmeterol reversed the effects of pyocyanin on cyclic AMP and ATP. 7. Mucociliary clearance is an important defence mechanism of the airways against bacterial infection. Salmeterol may benefit patients colonized by P. aeruginosa, not only by its bronchodilator action, but also by protecting epithelial cells from pyocyanin-induced slowing of CBF

Haemophilus influenzae infection of human respiratory mucosa in low concentrations of antibiotics

We examined the effects of 0.25 and 0.5 minimal inhibitory concentrations (MIC) of amoxicillin, loracarbef, and ciprofloxacin on the interaction of a clinical isolate of nontypable Haemophilus influenzae (NTHi) with human adenoid organ culture. Adenoid tissue was embedded in agar so that only the mucosal surface was exposed. Minimum essential medium containing NTHi with or without antibiotics was added to the organ culture and incubated with 5% CO2 at 37 degrees C for 24 h. The organ cultures (n = 6) were assessed for several parameters by light microscopy (LM) and transmission electron microscopy (TEM). Bacterial viable counts after 24 h were not significantly different in all organ cultures. Compared with uninfected controls at 24 h, infection with NTHi caused significant (p &lt; 0.05) damage to epithelium as assessed by LM: reduced ciliary beat frequency (CBF), disruption of epithelium integrity, and reduced number of ciliated sites. TEM showed extrusion of cells from the epithelial surface, loss of cilia from ciliated cells, cytoplasmic blebbing, and mitochondrial damage. In the presence of 0.25 and 0.5 MIC of all three antibiotics, the mucosal damage was significantly less (p &lt; 0.05). We conclude that in the presence of sub-MIC levels of amoxicillin, loracarbef, and ciprofloxacin, NTHi infection causes less functional (CBF) and structural damage.</p

Assessing immune function in adult bronchiectasis

Bronchiectasis is characterized by chronic airway infection and damage and remains an important health problem. Recent literature has emphasized the role of host defence and immune deficiency in the pathogenesis of bronchiectasis, but there have been few studies of immune function in adult bronchiectasis. A comprehensive screen of immune function was conducted in 103 adult patients with bronchiectasis, encompassing full blood examinations, immunoglobulins and IgG isotypes, complement levels, lymphocyte subsets and neutrophil function. Full blood examinations were normal in this cohort, as were complement levels. Statistical analysis confirmed that a significant number of subjects had low levels of IgG3 (13 patients), B cell lymphocytes (six patients) and T helper cell lymphocytes (seven patients) when compared with controls (P< 0·05). The most common abnormality was found with testing of the neutrophil oxidative burst. All subjects had a normal neutrophil phagocytic function but 33 of the subjects had an oxidative burst that was below the normal range (P< 0001). Almost half the group (45 subjects) had abnormally low levels of one of these four parameters. The findings of low B cells, Th cells and oxidative burst in bronchiectasis are novel. The results emphasize the importance of immune function assessment for adult bronchiectasis