Extraintestinal pathogenic isolates ofEscherichia colido not possess active IgA₁, IgA₂, sIgA or IgG proteases

Abstract

Infections outside of the intestinal tract due to pathogenic strains of Escherichia coli result in significant morbidity, mortality and increased healthcare costs. The ability of these strains to cause both mucosal and systemic infections, as well as recurrent infections due to the same (homologous) strain suggests the hypothesis that strains of E. coli that cause infection outside of the intestinal tract possess proteases that are capable of cleaving IgA 1 , IgA 2 , sIgA or IgG. To test this hypothesis the ability of eight E. coli strains, isolated from sites outside of the urinary tract and 14 homologous and 11 heterologous strains of E. coli that were isolated from women with recurrent UTI, to cleave IgA 1 , IgA 2 , sIgA or IgG was evaluated. Our experimental design allowed for detection of cell-associated and secreted immunoglobulin proteases in both log and stationary phase. Surprisingly, none of these 33 human clinical isolates when grown in iron depleted Luria-Bertani medium or human urine were able to degrade the immunoglobulins assessed. Despite previous studies suggesting otherwise, the findings from this study support the concept that strains of E. coli that cause infection outside of the intestinal tract do not possess proteases that cleave the human immunoglobulins IgA 1 , IgA 2 , sIgA or IgG.

Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli

“…Adhesins associated with host interaction, for example P fimbriae (37) and type 1 pilus subunits (38), were able to confer protection in animal models but failed in phase II clinical trials. Whole-cell preparations are available against ExPEC (39) and killed genetic engineered strains are still a matter of study (40). Other antigens considered for vaccines are the outer membrane proteins associated with iron uptake, such as IroN (41), Hma, IreA, IutA (42), FyuA, and other hypothetical TonB-dependent receptors (43).…”

Measurement of allergen-specific secretory IgA in stool of neonates, infants and toddlers by protection against degradation of immunoglobulins and allergens

“…The activities of various protease(s) in stool of neonates, infants and toddlers and the reduction of immunofluorescence signals of SIgA and IgA by stool protease(s) were to a large extent inhibited by PMSF and in part by leupeptin, but not by the other inhibitors tested in this study. The inhibitor spectrum indicates that protease(s) present in stool that degrade IgA, SIgA and allergens may be exogenous proteases, such as IgA1, IgA2, SIgA or IgG proteases in Escherichia coli (17,18) and other microbiota, rather than being leupeptin-and chymostatin-sentitive pancreatic proteases, trypsin and chymotrypsin, respectively. In this regard, reduced IgA immunofluorescence signals were not detected in the stool of 3day-old neonates probably because of immaturity (30).…”

“…To monitor the immunological maturity of the gut, it is important to measure antigenor allergen-specific SIgA levels in stool of patients with gastrointestinal food allergies and assess immunotolerance of allergy in the mucosa (13,14). For accurate quantitative measurement of SIgA in stool, the roles of pancreatic enzymes should be taken into consideration, such as trypsin, chymotrypsin (15,16), and various immunoglobulin -degrading proteases, such as IgA1, IgA2, SIgA or IgG proteases, in Escherichia coli (17,18) and other microbiota in stool.…”