Outer Membrane Protein Expression Profile in Helicobacter pylori Clinical Isolates

Abstract

The gram-negative gastric pathogen Helicobacter pylori is equipped with an extraordinarily large set of outer membrane proteins (OMPs), whose role in the infection process is not well understood. The Hop (Helicobacter outer membrane porins) and Hor (Hop-related proteins) groups constitute a large paralogous family consisting of 33 members. The OMPs AlpA, AlpB, BabA, SabA, and HopZ have been identified as adhesins or adherenceassociated proteins. To better understand the relevance of these and other OMPs during infection, we analyzed the expression of eight different omp genes (alpA, alpB, babA, babB, babC, sabA, hopM, and oipA) in a set of 200 patient isolates, mostly from symptomatic children or young adults. Virtually all clinical isolates produced the AlpA and AlpB proteins, supporting their essential function. All other OMPs were produced at extremely variable rates, ranging from 35% to 73%, indicating a function in close adaptation to the individual host or gastric niche. In 11% of the isolates, BabA was produced, and SabA was produced in 5% of the isolates, but the strains failed to bind their cognate substrates. Interleukin-8 (IL-8) expression in gastric cells was strictly dependent on the presence of the cag pathogenicity island, whereas the presence of OipA clearly enhanced IL-8 production. The presence of the translocated effector protein CagA correlated well with BabA and OipA production. In conclusion, we found unexpectedly diverse omp expression profiles in individual H. pylori strains and hypothesize that this reflects the selective pressure for adhesion, which may differ across different hosts as well as within an individual over time.

Helicobacter pylori AlpA and AlpB Bind Host Laminin and Influence Gastric Inflammation in Gerbils

“…Valkonen and colleagues found that N-acetylneuraminyllactose, sialylated fetuin, and certain other molecules significantly inhibited binding, suggesting an interaction between an H. pylori surface protein and glycosylated portions of laminin (59). Odenbreit and colleagues showed that mutation of the sabA gene in strain J99 abrogated laminin binding in a dot blot overlay assay, suggesting that SabA could also bind laminin (37). The sabA gene is reportedly not expressed in strain 26695 (37), and expression of sabA in strain SS1 has not been determined.…”

“…Odenbreit and colleagues showed that mutation of the sabA gene in strain J99 abrogated laminin binding in a dot blot overlay assay, suggesting that SabA could also bind laminin (37). The sabA gene is reportedly not expressed in strain 26695 (37), and expression of sabA in strain SS1 has not been determined.…”

“…A subsequent study revealed that alpAB mutants were defective in adherence to human gastric tissue sections (39). The alpAB locus was also found to be ubiquitously present in H. pylori strains and expressed during both mouse and human infections (37,44). In addition to its influence on adherence, the alpAB locus has been shown to influence host cell signaling and cytokine production (30,35,47).…”

Divergent Mechanisms of Interaction of Helicobacter pylori and Campylobacter jejuni with Mucus and Mucins

“…H. pylori also binds to sialyl-Lewis x via the SabA outer membrane protein (OMP) (10). H. pylori exhibits high genomic plasticity due to high rates of mutation and homologous recombination (11,12). Individual strains have been shown to modulate both their own adhesin expression and host glycan expression following infection (13,14).…”

Rapid evolution of distinctHelicobacter pylorisubpopulations in the Americas

“…Interestingly, several of these variants were common for Latin American isolates regardless of which ancestral population they belonged to. AlpB is an adhesin binding to laminins in the extracellular matrix [22] that is present in all H. pylori strains [23]. Together with AlpA, it is required for colonization in experimental models and for efficient adhesion to gastric epithelial cells [24].…”