Letters to the Editor

Pseudomonas aeruginosa exotoxin A antibodies in rapidly deteriorating chronic leg ulcers

Chronic pulmonary colonisation with Pseudomonas aeruginosa (PA) in patients with CF is associated with a high morbidity and mortality. Adequate treatment of first acquisition of PA might prevent or postpone chronic colonisation. Early detection of PA is therefore of major importance. Currently, cultures of oropharynx or sputum are most commonly practised. However, oropharyngeal culture has limitations both in the positive and negative predictive value for the presence of PA in the lower respiratory tract. Induction of sputum has little benefit in detection of PA. Serology might have additional value in early detection, when bacterial density is too low to be detected by culture. Molecular techniques are not yet widespread used for detection of PA, but have in general a high sensitivity. In this review, we describe the value of different diagnostic techniques for detecting PA.

To elucidate cellular mechanisms of myocardial depression inPseudomonassepsis, the effects of sublethal concentrations ofP. aeruginosaexotoxin A—a main virulence factor—were studied in cultured neonatal rat cardiomyocytes. It is known that this toxin exerts its pathogenic effect by inhibition of protein synthesis via ADP-ribosylation and thereby inactivation of elongation factor 2 (EF-2). Within 48–72 h, half maximal inhibition of protein synthesis occurs at 4–10 ng/ml. The toxin prevents theβ-adrenoceptor(AR)-mediated myosin heavy chain isozyme shift (V₃/V₁), while the T₃-induced myosin shift is not suppressed. Whileβ₁-AR-downregulation by excess of norepinephrine (NE) is not affected, protein synthesis-dependent receptor upregulation in the recovery period after removal of NE is completely suppressed byP. aeruginosaexotoxin A. Thus, a non-lethal, partial inhibition of global cellular protein synthesis byP. aeruginosaexotoxin A: (1) completely preventsβ₁-AR-mediated myosin isozyme shift andβ-AR upregulation; (2) sustains the cardiomyocytes in a catecholamine-refractory contractile state in the recovery period after catecholamine desensitization; (3) suggests cellular mechanisms by whichP. aeruginosaexotoxin A might impair heart function inPseudomonassepsis; and (4) may help reveal the possible influence of endogenous inhibitors of EF-2.