Chapter 9 : Immunoglobulin A1 Proteases of Pathogenic and Commensal Bacteria of the Respiratory Tract

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The three principal causes of bacterial meningitis, , , and , produce an IgA1 protease. In addition, IgA1 proteases are produced by two urogenital pathogens, five species of commensal gram-positive cocci found in the pharynx and oral cavity, , and all human-associated species of the genera and . In accordance with the substrate specificity of IgA1 proteases, humans and hominoid primates are the exclusive hosts of the bacteria that produce these enzymes. This chapter presents the hypothesis that invasive infection in occasional individuals is a result of nonsynchronized induction of the two types of antibodies by successive encounters with two different microorganisms: (i) colonization in the gut or upper respiratory tract with bacteria expressing surface epitopes similar or identical to those of the respective pathogen (e.g., K100 in the case of type b, and K1 or in the case of group B), and (ii) subsequent colonization with the actual pathogen. As a result of the prior colonization with a cross-reactive microorganism, the pathogen encounters preexisting IgA1 antibodies to its surface epitopes but no antibodies that will neutralize its IgA1 protease. IgA1s of humans and hominoid primates were the only known substrates of IgA1 proteases until recently. Now other permissive substrates have been revealed. Most of these are proteins of immunological relevance, but for some of the substrates, their accessibility to IgA1 protease in vivo is a matter of speculation.

Citation: Kilian M, Reinholdt J. 2005. Immunoglobulin A1 Proteases of Pathogenic and Commensal Bacteria of the Respiratory Tract, p 119-129. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch9
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Figure 1

Sites of IgA1 protease-induced cleavage within the hinge region of human IgA. Note that strains of and may cleave either a Pro-Ser peptide bond (type 1 protease) or a Pro-Thr peptide bond (type 2 protease). The IgA protease cleaves both IgA1 and the IgA2 allotype A2m( ), as indicated by the arrow. The shaded circles indicate carbohydrate side chains in the IgA1 hinge region, those that are hatched being variably present in IgA1 molecules. Species indicated by an asterisk show variable IgA1 protease activity.

Citation: Kilian M, Reinholdt J. 2005. Immunoglobulin A1 Proteases of Pathogenic and Commensal Bacteria of the Respiratory Tract, p 119-129. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch9
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Image of Figure 2
Figure 2

Phylogeny of IgA1 protease and paralogous genes of (a) and and (b). Note that the strain Rd gene has a mutation resulting in a stop codon in the middle of the gene. The sequences from (AJ001739 and AJ001740) are 578-bp fragments reminiscent of the /gene family (not shown).

Citation: Kilian M, Reinholdt J. 2005. Immunoglobulin A1 Proteases of Pathogenic and Commensal Bacteria of the Respiratory Tract, p 119-129. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch9
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Figure 3

Hypothetical model for induction of susceptibility to invasive infection with IgA1 protease-producing pathogens. (A) Colonization with a nonpathogen with a cross-reactive surface antigen, resulting in the induction of IgA1 antibodies. (B) Colonization with an IgA1 protease-producing pathogen, resulting in elimination of IgA1-mediated protection and blockage of intact antibodies.

Citation: Kilian M, Reinholdt J. 2005. Immunoglobulin A1 Proteases of Pathogenic and Commensal Bacteria of the Respiratory Tract, p 119-129. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch9
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Table 1

Bacterial IgA proteases grouped according to enzyme characteristics and phylogenic relationships

Citation: Kilian M, Reinholdt J. 2005. Immunoglobulin A1 Proteases of Pathogenic and Commensal Bacteria of the Respiratory Tract, p 119-129. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch9

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