is normally a gram-negative bacterium that persistently colonizes more than half of the global human population. bacterium persistently colonizes the human stomach (34 145 153 217 colonization of the stomach elicits ML 228 humoral and cellular ML 228 immune responses (28 52 129 180 which in most cases do not result in bacterial clearance. In the absence of antibiotic therapy can persist in the human stomach for decades or for an entire lifetime (116). is usually widespread throughout the world and is present in about 50% of the global human population (178 226 and discuss mechanisms by which evades immune clearance. ANTIBACTERIAL PROPERTIES OF THE HUMAN STOMACH Humans ingest many microorganisms each day but most cannot successfully colonize the stomach. One of the most important antibacterial properties of the human stomach is usually its acidic pH. Under fasting conditions the human gastric luminal pH is usually <2 which prevents the proliferation of bacteria within the gastric lumen. Within the gastric mucus layer overlying gastric epithelial cells a pH gradient exists ranging from a pH of about 2 at the luminal surface to a pH of between 5 and 6 at the epithelial cell surface (185 225 After entering the stomach penetrates the gastric mucus layer (203) and thereby encounters a less acidic environment than that which is present within the gastric lumen. typically does not traverse the epithelial barrier (97) and it is classified as a noninvasive bacterial organism. Within the gastric mucus layer most organisms are free living but some organisms attach to the apical surface of gastric epithelial cells and may occasionally be internalized by these cells (10 97 119 173 Multiple factors produced by the gastric mucosa limit the proliferation of bacteria (Fig. ?(Fig.1).1). Antibacterial peptides including β-defensins 1 and 2 and LL-37 are active against many different species of bacteria (74 94 Lactoferrin inhibits bacterial growth by restricting the availability of extracellular Fe3+ (133) and can have direct effects on bacterial membrane permeability (13 175 253 Lactoferricin a peptide derived from lactoferrin also has antimicrobial properties (80). Lysozyme can degrade the peptidoglycan of many bacterial species. Surfactant protein D is capable of aggregating many different types of microorganisms in a calcium-dependent and lectin-specific manner (114 158 164 Finally specific components of human gastric mucin can inhibit bacterial growth; alpha-1 4 O-glycans inhibit biosynthesis of cholesteryl-α-d-glucopyranoside a component of the cell wall (112). FIG. 1. Antibacterial properties of the stomach. The stomach ML 228 is usually intrinsically resistant to bacterial colonization. Factors which contribute to this resistance include gastric acidity lactoferrin and antibacterial peptides (LL-37 β-defensin 1 and β-defensin … Toll-like receptors (TLRs) are present on the surface of gastric epithelial cells and can recognize pathogen-associated molecular patterns (PAMPs) (21 201 216 If bacteria invade and penetrate the gastric epithelial barrier the CSP-B alternate pathway of complement is activated and invading bacteria encounter macrophages and neutrophils. Since most organisms localize within the gastric mucus layer and do not invade gastric tissue contact between and phagocytic cells probably occurs infrequently unless there are disruptions in the gastric epithelial barrier. The antibacterial properties of the human stomach described above prevent most bacterial species from colonizing the stomach. Based on the high prevalence of in humans throughout the world it may be presumed that possesses mechanisms to overcome these innate host defenses. FACTORS THAT CONTRIBUTE TO GASTRIC COLONIZATION The capacity of to colonize the human stomach can be attributed to the production of specific bacterial products (Fig. ?(Fig.2).2). Numerous components have been designated colonization factors based on the demonstration that null mutant strains defective in the production of these factors are impaired in the ability to colonize the stomach in animal models. For example null mutant strains defective in production of urease or flagella are unable to colonize animal models ML 228 (59 62.