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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normally, the mucosa of the nasooropharynx, trachea, and, perhaps, the major bronchi is colonized with aerobic and anaerobic microbes. This epithelial surface coexists with the microbial flora and is not overgrown with it. Moreover, the physiologic functions of the mucosa--including a protective barrier, mucociliary clearance and humidification, and warming of respired air--are not impeded. How this flora is controlled and what is amiss when virulent or pathogenic bacteria can cause infection are fascinating questions. A balance is maintained during health in which epithelial cell integrity--a function of proper nutrition, available secretory immunoglobulins and glycoproteins, and ciliary motion--resists the microbe's attempt to attach via specialized receptors (pili) or by proteolytic destruction of local proteins. These interactions are reviewed in detail. When colonization is excessive and aspiration of more microbes into the lower airway occurs, infection is more probable. Certain bacteria such as Streptococcus pneumoniae and Hemophilus influenzae, which are associated with chronic bronchitis, illustrate a mechanism in which the host-microbial balance may be upset by selective impairment of a host protein, secretory IgA1. Alternatively, viral infection or cilotoxic microbes (mycoplasma) can favor colonization of bacteria when mucosal clearance mechanisms are impaired. Last, mucosal integrity can be breached by noxious gases or inflammation that may allow bacteria entry into the submucosal that provides a nidus for infection.
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PMID:Bacterial adherence to respiratory tract mucosa--a dynamic interaction leading to colonization. 332 Dec 69

Haemophilus influenzae is one of several bacterial pathogens known to release IgA1 proteases into the extracellular environment. Each H. influenzae isolate produces one of at least three distinct types of these enzymes that differ in the specific peptide bond they cleave in the hinge region of human IgA1. We have isolated the gene specifying type 1 IgA1 protease from a total genomic library of H. influenzae, subcloned it into plasmid vectors, and introduced these vectors into Escherichia coli K-12. The enzyme synthesized by E. coli was active and had the same specificity as that of the H. influenzae donor. Unlike that of the donor, E. coli protease activity accumulated in the periplasm rather than being transported extracellularly. The position of the protease gene in H. influenzae DNA and its direction of transcription was approximated by deletion mapping. Tn5 insertions, and examination of the polypeptides synthesized by minicells. A 1-kilobase probe excised from the IgA1 protease gene hybridized with DNA restriction fragments of all H. influenzae serogroups but not with DNA of a nonpathogenic H. parainfluenzae species known to be IgA1 protease negative.
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PMID:IgA1 proteases of Haemophilus influenzae: cloning and characterization in Escherichia coli K-12. 634 96

The production of immunoglobulin A (IgA) protease is a potentially useful marker in differentiating pathogenic from nonpathogenic species of clinical isolates; however, current quantitative assay methods are too tedious for routine application. A simple quantitative method was developed to screen clinical isolates for IgA protease production. This method is based on the specificity of reaction between IgA and alpha chain-specific antiserum in an immunochemistry analyzer (Beckman Instruments, Inc., Brea, Calif.). Colonies of IgA protease producers (Streptococcus sanguis, Streptococcus pneumoniae, Neisseria gonorrhoeae, Neisseria meningitidis, and Haemophilus influenzae) were picked from solid media, transferred to brain heart infusion containing IgA1, and incubated at 37 degrees C for at least 2 h to provide a detectable decrease in IgA concentration. The standard deviation for randomly picked colonies within a species was about +/- 15%. Several IgA protease-negative species caused no detectable reduction in the IgA content of the system. The specificity of the IgA measurement eliminates the requirements for extensive purification and radiolabeling of substrate and provides the basis for a well-defined IgA protease activity unit (micrograms of IgA1 cleaved per minute per milliliter of culture).
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PMID:Quantitative screening of clinical isolates for immunoglobulin A protease production. 635 34

IgA1 proteases of two distinct specificities were demonstrated among 95 isolates of Haemophilus influenzae and nine isolates of H. aegyptius. The two enzymes cleaved two different peptide bonds in the hinge region of the alpha chain of IgA1: a prolyl-seryl bond located at position 231-232 (type A cleavage) and a prolyl-threonyl peptide bond between residues 235 and 236 (type B cleavage). Each strain of H. influenzae produced either one or both of these types of enzymes, whereas all H. aegyptius strains produced type A enzyme only. The application of enzyme-neutralizing antibodies to the study of IgA1 proteases produced by the 104 strains of H. influenzae and H. aegyptius revealed at least 15 different types of protease activities based on inhibition patterns in nine selected antibody preparations. The types of IgA1 proteases closely correlated with the serotype of encapsulated strains of H. influenzae. The study suggests that H. influenzae strains produce at least two serologically different IgA1 proteases with distinct or identical enzymatic activities.
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PMID:Molecular biology of Haemophilus influenzae IgA1 proteases. 635 64

The characteristics and functions of microbial IgA proteases are reviewed. These enzymes represent a structurally heterogeneous group of proteins that are secreted into the extracellular environment by bacteria capable of causing human disease. The IgA proteases, which vary in their requirements for metal ions, are neutral endopeptidases whose role in the infectious process is not known but whose pronounced substrate specificity for human proteins of the IgA1 subclass has repeatedly been demonstrated. As reagents, the IgA proteases are useful in cleaving IgA molecules to yield intact Fc alpha and Fab alpha fragments that will allow the study of the structure and function of the two large regions of IgA immunoglobulin proteins. The role, if any, of these enzymes in promoting infection by pathogenic members of the genera Neisseria, Hemophilus, and Streptococcus is not known, although the secretory immune system is primarily mediated by antibodies of the IgA isotype, among which are IgA1 subclass proteins, and these proteins are susceptible to cleavage by IgA protease. The determination of the role of these enzymes in the pathogenesis of human infection must await clearer understanding of antigenicity and antibody function at secretory sites and of the relative roles of the two subclasses of human IgA in immune defense.
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PMID:Secretory immunity and the bacterial IgA proteases. 679 82

Haemophilus influenzae is one of five bacterial species known to produce IgA proteases, enzymes that specifically cleave the human IgA1 heavy chain. Strains of H. influenzae produce three distinct types of IgA proteases that cleave different peptide bonds within the IgA1 hinge region. Type 1 protease cleaves the prolyl-seryl bond at position 231-232; type 2 protease cleaves the prolyl-threonyl bond at position 235-236, the same bond attacked by Neisseria gonorrhoeae and Neisseria meningitidis type 2 proteases. Type 3 protease yields a unique double Fd cleavage pattern; the exact peptide bonds cleaved have not been determined. The type of protease produced correlates with the serotype, but not with the biotype, of the isolate; serotypes A, B, D, and F produce primarily type 1 protease, whereas serotypes C and E produce only type 2 enzyme. Each nontypable strain yields one of the three protease types. These data further extend our knowledge of the extreme specificity of the IgA proteases and suggest that IgA protease type may be useful in the taxonomy and epidemiology of H. influenzae.
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PMID:Relationship between the specificity of IgA proteases and serotypes in Haemophilus influenzae. 680 43

Streptococcus pneumoniae and Haemophilus influenzae are among the most common bacterial pathogens responsible for respiratory tract infections in otherwise healthy humans. Thirty-six strains of S. pneumoniae, 62 strains of H. influenzae, six hospital-acquired respiratory pathogens, and a strain of Streptococcus pyogenes were examined for production of IgA protease, a bacterial enzyme whose only known substrate is human IgA1. IgA protease was produced by 100% of the isolates of S. pneumoniae and 98% of the isolates of H. influenzae. The enzyme from both species cleaved human serum and secretory IgA1 proteins, but not human IgA2, IgG, or human serum albumin. None of the hospital-acquired pathogens had detectable IgA protease activity, a finding indicating that the production of this enzyme distinguishes S. pneumoniae and H. influenzae from the opporunistic respiratory pathogens.
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PMID:Specific proteolysis of human IgA by Streptococcus pneumoniae and Haemophilus influenzae. 698 25

A new method is described for the detection of bacterial immunoglobulin A (IgA) protease which splits IgA into Fab and Fc fragments. The method takes advantage of a recent finding that receptors for IgA fragments occur commonly among type 4 group A streptococci. The bacterial preparation to be tested for protease activity was first incubated with radiolabeled purified IgA1 myeloma protein, and the proportion of radioactivity bound to a standard suspension of the streptococci was then measured. Since isolated Fab fragments do not bind to streptococcal IgA receptors, a decrease in the amount of radioactivity bound to the streptococci, as compared with the amount before digestion, indicates the presence of protease in the test preparation. Using this method, protease activity was detected in Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus sanguis, but not in Escherichia coli or Branhamella catarrhalis.
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PMID:New method that uses binding of immunoglobulin A to group A streptococcal immunoglobulin A Fc receptors for demonstration of microbial immunoglobulin A protease activity. 701 17

In addition to Ipa proteins and IcsA, which are involved in entry into epithelial cells and intercellular spread, respectively, Shigella secretes a 110 kDa protein, designated SepA. We report the identification, cloning, and nucleotide sequence determination of the sepA gene, analysis of SepA secretion, and construction and characterization of a sepA mutant. The sepA gene is carried by the virulence plasmid and codes for a 150 kDa precursor. Upon secretion, which does not involve accessory proteins encoded by the virulence plasmid, the precursor is converted to a mature protein of 110 kDa by two cleavages removing an N-terminal signal sequence and a C-terminal fragment. Extensive similarities were detected between the sequence of the first 500 residues of mature SepA and the N-terminal region of IgA1 proteases from Neisseria gonorrhoeae and Haemophilus influenzae, the Tsh haemagglutinin of an avian pathogenic Escherichia coli, and the Hap protein involved in adhesion and penetration of H. influenzae. The C-terminal domain of the SepA precursor, which is not present in the secreted protein, exhibits sequence similarity with pertactin of Bordetella pertussis and the ring-forming protein of Helicobacter mustelae. Construction and phenotypic characterization of a sepA mutant indicated that SepA is required neither for entry into cultured epithelial cells nor for intercellular dissemination. However, in the rabbit ligated ileal loop model, the sepA mutant exhibited an attenuated virulence, which suggests that SepA might play a role in tissue invasion.
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PMID:SepA, the major extracellular protein of Shigella flexneri: autonomous secretion and involvement in tissue invasion. 747 98

The respiratory mucosa is protected primarily by a secretory immune system that is under complex and only partly understood immunoregulatory control. Secretory immunoglobulins (SIgA and SIgM) protect the mucosal surface by immune exclusion of antigens. However, the fact that most IgA produced in the respiratory tract belongs to the IgA1 subclass renders SIgA in this region susceptible to IgA-specific proteases produced by Haemophilus influenzae, Streptococcus pneumonia, and Neisseria meningitidis. Immunoglobulin G can also perform immune exclusion at respiratory surfaces but, like IgE, it reaches the secretions merely by passive diffusion. The phlogistic properties of antibodies belonging to these classes explain their potential involvement in maintaining mucosal inflammation. In patients with selective IgA deficiency, SIgA is lacking and is not regularly compensated for satisfactorily by SIgM. In such patients unexplained immunoregulatory mechanisms, perhaps involving the local microbiota, give rise to a large number of IgD-producing cells in the upper respiratory tract. Immunoglobulin D cannot act as a secretory antibody and might block the protective properties of IgG; this could explain why these patients are particularly prone to recurrent infections. Our observations show that there are large individual variations in the mucosal immune system with regard to humoral immunity in the upper respiratory tract.
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PMID:The role of humoral mucosal immunity in the induction and maintenance of chronic airway infections. 776 61


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