• Compound
• Helicobacter
• Helicobacter-associated gastritis
• Inflammation
• Phytotherapy
• Plant extract

• CI2021A00606 Scientific and Technological Innovation Project, China Academy of Chinese Medical Sciences
• CACM-(2022-QNRC2-B06) Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine
• DZMG-QNGG0005 Funding for Clinical Research at High-Level Traditional Chinese Medicine Hospitals in China Central
• YZX-202237 Fundamental Research Funds for the Central Public Welfare Research Institutes
• YZX-202241 Fundamental Research Funds for the Central Public Welfare Research Institutes
• 2015-JC-31 Beijing Traditional Chinese Medicine Inheritance "3 + 3 Project"
• Beijing Traditional Chinese Medicine Inheritance “3 + 3 Project”

• Ced
• Crenarchaea
• DNA damage response
• Ups
• chromosomal DNA exchange

• National Natural Science Foundation of China

• Helicobacter pylori
• CagA
• Endodontics
• HtrA
• Root canal
• VacA

• Humans
• Helicobacter pylori/genetics
• Helicobacter pylori/physiology
• Tooth, Deciduous/microbiology
• Child
• Dental Pulp Cavity/microbiology
• Phylogeny
• Child, Preschool
• Female

• 953000-016 Deutsche Gesellschaft für Zahn-, Mund- und Kieferheilkunde
• Friedrich-Alexander-Universität Erlangen-Nürnberg (1041)

• Carcinogenic toxin
• Deep learning algorithm
• Gastric cancer
• Helicobacter pylori
• Serum antibody
• Surface-enhanced Raman spectrometry

• ASPP2
• CagA
• Cell polarity
• Cortactin
• Par1b
• T4SS
• Tight junction
• ZO-1

• High throughput
• Host-pathogen interactions
• Laboratory-based techniques
• Mass spectrometry
• Protein-protein interaction

• Host-Pathogen Interactions
• Humans
• High-Throughput Screening Assays/methods
• Animals
• Bacterial Proteins/metabolism
• Protein Interaction Mapping/methods

• MR/X00161X/1 Medical Research Council

• Helicobacter pylori
• Adhesins
• Gastric ulcer
• OMVs
• Pathogenesis
• Virulence factors

• Humans
• Virulence/genetics
• Helicobacter pylori/genetics
• Peptic Ulcer/microbiology
• Stomach Neoplasms
• Virulence Factors/genetics
• Bacterial Proteins/genetics
• Antigens, Bacterial/genetics

• Helicobacter pylori
• bacterial secretion system
• effector protein
• gastric cancer
• inflammation

• Animals
• Humans
• Bacterial Proteins/metabolism
• Antigens, Bacterial/genetics
• Antigens, Bacterial/metabolism
• Helicobacter pylori/genetics
• Stomach Neoplasms
• Genomic Islands
• Gastrointestinal Microbiome
• Peptic Ulcer/complications
• Helicobacter Infections/complications

• T32 GM008320 NIGMS NIH HHS
• T32 AI112541 NIAID NIH HHS
• P01 CA116087 NCI NIH HHS
• R01 AI118932 NIAID NIH HHS
• R01 AI039657 NIAID NIH HHS
• I01 BX004447 BLRD VA

• ADP-heptose
• Bacteria
• Inflammation
• Lysosome
• NF-κB
• Proteasome
• Ubiquitin

• infection
• pathogens
• x-ray crystallography

• CagA
• EPIYA motifs
• Gastric cancer
• Helicobacter pylori
• Hit-and-run carcinogenesis
• Virulence factors

• Staphylococcus aureus
• biomarkers
• diabetes
• early diagnosis
• immunoproteomics
• infections

• Cytotoxin associated antigen A
• Gastric cancer
• Helicobacter pylori
• Nickel-regulated small RNA
• Small regulatory RNAs
• Virulence factors

The human pathogen Helicobacter pylori represents a risk factor for the development of gastric diseases including cancer. The H. pylori-induced transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is involved in the pro-inflammatory response and cell survival in the gastric mucosa, and represents a trailblazer of gastric pathophysiology. Termination of nuclear NF-κB heterodimer RelA/p50 activity is regulated by the ubiquitin-RING-ligase complex elongin-cullin-suppressor of cytokine signalling 1 (ECS^SOCS1), which leads to K48-ubiquitinylation and degradation of RelA. We found that deubiquitinylase (DUB) ubiquitin specific protease 48 (USP48), which interacts with the COP9 signalosome (CSN) subunit CSN1, stabilises RelA by deubiquitinylation and thereby promotes the transcriptional activity of RelA to prolong de novo synthesis of DUB A20 in H. pylori infection. An important role of A20 is the suppression of caspase-8 activity and apoptotic cell death. USP48 thus enhances the activity of A20 to reduce apoptotic cell death in cells infected with H. pylori. Our results, therefore, define a synergistic mechanism by which USP48 and A20 regulate RelA and apoptotic cell death in H. pylori infection.

• Apoptotic cell death
• COP9 signalosome (CSN)
• Deubiquitinylase (DUB)
• Nedd8
• RelA

Helicobacter pylori is a pathogen that colonizes the stomach and causes chronic gastritis. Helicobacter pylori can colonize deep inside gastric glands, triggering increased R‐spondin 3 (Rspo3) signaling. This causes an expansion of the “gland base module,” which consists of self‐renewing stem cells and antimicrobial secretory cells and results in gland hyperplasia. The contribution of Rspo3 receptors Lgr4 and Lgr5 is not well explored. Here, we identified that Lgr4 regulates Lgr5 expression and is required for H. pylori‐induced hyperplasia and inflammation, while Lgr5 alone is not. Using conditional knockout mice, we reveal that R‐spondin signaling via Lgr4 drives proliferation of stem cells and also induces NF‐κB activity in the proliferative stem cells. Upon exposure to H. pylori, the Lgr4‐driven NF‐κB activation is responsible for the expansion of the gland base module and simultaneously enables chemokine expression in stem cells, resulting in gland hyperplasia and neutrophil recruitment. This demonstrates a connection between R‐spondin‐Lgr and NF‐κB signaling that links epithelial stem cell behavior and inflammatory responses to gland‐invading H. pylori.

• Helicobacter pylori
• Lgr4
• Lgr5
• NF-κB
• R-spondin 3

• bacteria
• fungi
• infectious diseases
• organoid
• parasites
• pathogenesis
• prions
• viruses

• CagA
• Helicobacter pylori
• curcumin
• metabolic transformation
• reduced curcumin

• Animals
• Antigens, Bacterial/metabolism
• Bacterial Proteins/genetics
• Bacterial Proteins/metabolism
• Curcumin/pharmacology
• Epithelial Cells/metabolism
• Escherichia coli/metabolism
• Helicobacter Infections
• Helicobacter pylori/genetics
• Helicobacter pylori/metabolism
• Mice
• Phosphorylation

• I01 CX002171 CSRD VA
• P01 CA028842 NCI NIH HHS
• P01 CA116087 NCI NIH HHS
• D43 TW009345 FIC NIH HHS
• P30 DK058404 NIDDK NIH HHS

Production and secretion of pertussis toxin (PT) is essential for the virulence of Bordetella pertussis. Due to the large oligomeric structure of PT, transport of the toxin across bacterial membrane barriers represents a significant hurdle that the bacteria must overcome in order to maintain pathogenicity. During the secretion process, PT undergoes a two-step transport process. The first step involves transport of the individual polypeptide chains of PT across the inner membrane utilizing a generalized secretion pathway, most likely the bacterial Sec system. The second step involves the use of a specialized apparatus to transport the toxin across the outer membrane of the bacterial cell. This apparatus, which has been termed the Ptl transporter and which is unique to the PT secretion pathway, is a member of the type IV family of bacterial transporters. Here, the current understanding of the PT secretion process is reviewed including a description of the Ptl proteins that assemble to form the transporter, the general structure of type IV transporters, the known similarities and differences between canonical type IV substrate transport and Ptl-mediated transport of PT, as well as the known sequence of events in the assembly and secretion of PT.

• pertussis toxin
• toxin secretion
• type IV secretion

• Biological Transport/physiology
• Bordetella pertussis/chemistry
• Bordetella pertussis/metabolism
• Membrane Transport Proteins/physiology
• Pertussis Toxin/biosynthesis
• Pertussis Toxin/toxicity
• Virulence Factors, Bordetella/biosynthesis
• Virulence Factors, Bordetella/toxicity

Helicobacter pylori infection constitutes one of the major risk factors for the development of gastric diseases including gastric cancer. The activation of nuclear factor‐kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) via classical and alternative pathways is a hallmark of H. pylori infection leading to inflammation in gastric epithelial cells. Tumor necrosis factor receptor‐associated factor (TRAF)‐interacting protein with forkhead‐associated domain (TIFA) was previously suggested to trigger classical NF‐κB activation, but its role in alternative NF‐κB activation remains unexplored. Here, we identify TRAF6 and TRAF2 as binding partners of TIFA, contributing to the formation of TIFAsomes upon H. pylori infection. Importantly, the TIFA/TRAF6 interaction enables binding of TGFβ‐activated kinase 1 (TAK1), leading to the activation of classical NF‐κB signaling, while the TIFA/TRAF2 interaction causes the transient displacement of cellular inhibitor of apoptosis 1 (cIAP1) from TRAF2, and proteasomal degradation of cIAP1, to facilitate the activation of the alternative NF‐κB pathway. Our findings therefore establish a dual function of TIFA in the activation of classical and alternative NF‐κB signaling in H. pylori‐infected gastric epithelial cells.

• ALPK1
• NIK
• TRAF
• cIAP1

Approximately 90% of new cases of noncardiac gastric cancer (GC) are related to Helicobacter pylori (H. pylori), and cytotoxin-associated gene A (CagA) is one of the main pathogenic factors. Recent studies have shown that the pharmacological effects of cryptotanshinone (CTS) can be used to treat a variety of tumors. However, the effects of CTS on H. pylori, especially CagA+ strain-induced gastric mucosal lesions, on the development of GC is unknown.

To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells, and determine if CagA+ H. pylori strains causes pathological changes in the gastric mucosa of mice.

The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8 (CCK-8) assay, and the abnormal growth, migration and invasion caused by CagA were detected by CCK-8 and transwell assays. After transfection with pSR-HA-CagA and treatment with CTS, proliferation and metastasis were evaluated by CCK-8 and transwell assays, respectively, and the expression of Src homology 2 (SH2) domain–containing phosphatase 2 (SHP2) and phosphorylated SHP2 (p-SHP2) was detected using western blotting in AGS cells. The enzyme-linked immunosorbent assay was used to determine the immunoglobulin G (IgG) level against CagA in patient serum. Mice were divided into four groups and administered H. pylori strains (CagA+ or CagA-) and CTS (or PBS) intragastrically, and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains. Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney.

CTS inhibited the growth of GC cells in dose- and time-dependent manners. Overexpression of CagA promoted the growth, migration, and invasion of GC cells. Importantly, we demonstrated that CTS significantly inhibited the CagA-induced abnormal proliferation, migration, and invasion of GC cells. Moreover, the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients. Additionally, CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells. CTS suppressed CagA+ H. pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA- H. pylori strain group.

CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro, and CagA+ H. pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.

• Cytotoxin associated gene A
• SHP2
• Cryptotanshinone
• Helicobacter pylori
• Chronic infection model

Helicobacter pylori (H. pylori) is a microaerophilic, Gram-negative, human gastric pathogen found usually in the mucous lining of stomach. It infects more than 50% of the world’s population and leads to gastroduodenal diseases. The outcome of disease depends on mainly three factors: Host genetics, environment and bacterial factors. Among these, bacterial virulence factors such as cagA, vacA are well known for their role in disease outcomes. However, based on the global epidemiological results, none of the bacterial virulence (gene) factors was found to be associated with particular diseases like duodenal ulcer (DU) in all populations. Hence, substantial importance has been provided for research in strain-specific genes outside the cag pathogenicity island, especially genes located within the plasticity regions. dupA found within the plasticity regions was first demonstrated in 2005 and was proposed for duodenal ulcer development and reduced risk of gastric cancer in certain geographical regions. Due to the discrepancies in report from different parts of the world in DU development related to H. pylori virulence factor, dupA became an interesting area of research in elucidating the role of this gene in the disease progression. In this review, we shed light on the detailed information available on the polymorphisms in dupA and their clinical relevance. We have critically appraised several pertinent studies on dupA and discussed their merits and shortcomings. This review also highlights dupA gene as an important biomarker for DU in certain populations.

• Helicobacter pylori
• Plasticity region
• Duodenal ulcer
• Gastric cancer
• dupA gene

• Antigens, Bacterial/genetics
• Bacterial Proteins/genetics
• Duodenal Ulcer/diagnosis
• Duodenal Ulcer/epidemiology
• Helicobacter Infections/epidemiology
• Helicobacter pylori/genetics
• Humans
• Stomach Neoplasms
• Virulence Factors/genetics

• Helicobacter pylori
• animal model
• animal models
• carcinogenesis
• gastric cancer
• gene regulation
• hit-and-run hypothesis
• type IV secretion system

• adhesion
• helicobacter pylori
• inflammation
• sulglycotide

• Animals
• Bacterial Adhesion/drug effects
• Bacterial Proteins
• Cattle
• Helicobacter Infections/drug therapy
• Helicobacter pylori/drug effects
• Humans
• Inflammation/drug therapy
• Sialoglycoproteins/pharmacology
• Swine

• Helicobacter pylori
• Inflammasome
• Interleukin-1β
• NLRP3

• DFG-grant A04 in CRC-1181 Deutsche Forschungsgemeinschaft

Helicobacter pylori colonizes human stomach mucosa and its infection causes gastrointestinal diseases with variable severity. Bacterial infection stimulates autophagy, which is a part of innate immunity used to eliminate intracellular pathogens. Several intracellular bacteria have evolved multipronged strategies to circumvent this conserved system and thereby enhance their chance of intracellular survival. Nonetheless, studies on H. pylori have produced inconsistent results, showing either elevated or reduced clearance efficiency of intracellular bacteria through autophagy. In this review, we summarize recent studies on the mechanisms involved in autophagy induced by H. pylori and the fate of intracellular bacteria.

• Autophagy
• Helicobacter pylori
• Intracellular survival
• Virulence factor

• Apoptosis
• Gastric cancer
• PTP1B
• Proliferation
• miR-146b

• ATPases
• Helicobacter pylori
• gastric cancer
• secretion systems

Toll-like receptor TLR5 recognizes a conserved domain, termed D1, that is present in flagellins of several pathogenic bacteria but not in Helicobacter pylori. Highly virulent H. pylori strains possess a type IV secretion system (T4SS) for delivery of virulence factors into gastric epithelial cells. Here, we show that one of the H. pylori T4SS components, protein CagL, can act as a flagellin-independent TLR5 activator. CagL contains a D1-like motif that mediates adherence to TLR5⁺ epithelial cells, TLR5 activation, and downstream signaling in vitro. TLR5 expression is associated with H. pylori infection and gastric lesions in human biopsies. Using Tlr5-knockout and wild-type mice, we show that TLR5 is important for efficient control of H. pylori infection. Our results indicate that CagL, by activating TLR5, may modulate immune responses to H. pylori.

Toll-like receptor TLR5 recognizes a domain, D1, that is present in flagellins of several pathogenic bacteria but not in Helicobacter pylori. Here, the authors show that TLR5 can be activated independently of flagellin by a component of the H. pylori type IV secretion system that contains a D1-like motif.

Chronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor for gastric cancer. The cagA gene product, CagA, is delivered into gastric epithelial cells via the bacterial type IV secretion system. Delivered CagA then undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in its C-terminal region and acts as an oncogenic scaffold protein that physically interacts with multiple host signaling proteins in both tyrosine phosphorylation-dependent and -independent manners. Analysis of CagA using in vitro cultured gastric epithelial cells has indicated that the nonphysiological scaffolding actions of CagA cell-autonomously promote the malignant transformation of the cells by endowing the cells with multiple phenotypic cancer hallmarks: sustained proliferation, evasion of growth suppressors, invasiveness, resistance to cell death, and genomic instability. Transgenic expression of CagA in mice leads to in vivo oncogenic action of CagA without any overt inflammation. The in vivo oncogenic activity of CagA is further potentiated in the presence of chronic inflammation. Since Helicobacter pylori infection triggers a proinflammatory response in host cells, a feedforward stimulation loop that augments the oncogenic actions of CagA and inflammation is created in CagA-injected gastric mucosa. Given that Helicobacter pylori is no longer colonized in established gastric cancer lesions, the multistep nature of gastric cancer development should include a “hit-and-run” process of CagA action. Thus, acquisition of genetic and epigenetic alterations that compensate for CagA-directed cancer hallmarks may be required for completion of the “hit-and-run” process of gastric carcinogenesis.

• Helicobacter pylori
• PAR1
• SHP2
• cagA/CagA
• inflammation
• “hit-and-run” carcinogenesis

• Adherens junction
• CagA
• E-cadherin
• Epithelial barrier
• HtrA serine protease
• Protease
• Tight junction
• Type IV secretion T4SS
• UreA
• VacA

• Inflammasome
• PAMP
• PRR
• T4SS
• TLR

• ARTS, artesunate
• Abbreviations: ART, artemisinin
• Artemisinin
• Artesunate
• CFU, colony forming units
• COX-2, cyclooxygenase-2
• DHA, dehydroartemisinin
• DMSO, dimethyl sulfoxide
• Dihydroartemisinin
• ELISA, enzyme-linked immunosorbent assay
• Gastric cancer
• Helicobacter pylori
• IARC, International Agency for Research on Cancer
• IL-8, interleukin-8
• MNU, N-methyl-N-nitroso-urea
• MOI, multiplicity of infection
• NF-κB signaling
• NF-κB, nuclear factor-κB
• PBS, phosphate buffer solution
• ROS, reactive oxygen species
• TNF-α, tumor necrosis factor-α

• Animals
• Anticarcinogenic Agents/pharmacology
• Artemisinins/pharmacology
• Artesunate/pharmacology
• Bacterial Adhesion/drug effects
• Cell Line, Tumor
• Cytokines/metabolism
• Helicobacter Infections/complications
• Helicobacter pylori/drug effects
• Helicobacter pylori/pathogenicity
• Humans
• Mice, Inbred C57BL
• Microbial Sensitivity Tests
• NF-kappa B/metabolism
• Reactive Oxygen Species/metabolism
• Stomach Neoplasms/microbiology
• Stomach Neoplasms/pathology
• Stomach Neoplasms/prevention & control

Helicobacter pylori plays an essential role in the pathogenesis of gastritis, peptic ulcer disease, and gastric cancer. The serine protease HtrA, an important secreted virulence factor, disrupts the gastric epithelium, which enables H. pylori to transmigrate across the epithelium and inject the oncogenic CagA protein into host cells. The function of periplasmic HtrA for the H. pylori cell is unknown, mainly due to unavailability of the htrA mutants. In fact, htrA has been described as an essential gene in this bacterium. We have screened 100 worldwide H. pylori isolates and show that only in the N6 strain it was possible to delete htrA or mutate the htrA gene to produce proteolytically inactive HtrA. We have sequenced the wild-type and mutant chromosomes and we found that inactivation of htrA is associated with mutations in SecA – a component of the Sec translocon apparatus used to translocate proteins from the cytoplasm into the periplasm. The cooperation of SecA and HtrA has been already suggested in Streptococcus pneumonia, in which these two proteins co-localize. Hence, our results pinpointing a potential functional relationship between HtrA and the Sec translocon in H. pylori possibly indicate for the more general mechanism responsible to maintain bacterial periplasmic homeostasis.

The gastric pathogen and carcinogen Helicobacter pylori(H. pylori) encodes a type IV secretion system for translocation of the effector protein CagA into host cells. Injected CagA becomes tyrosine-phosphorylated at the five amino acid residue Glutamate-Proline- Isoleucine-Tyrosine-Alanine (EPIYA)-sequence motifs. These phosphorylated EPIYA-sites represent recognition motifs for binding of multiple host factors, which then manipulate signaling pathways to trigger gastric disease. Thus, efficient detection of single phosphorylated EPIYA-motifs in CagA is required. Detection of phospho-CagA is primarily performed using commercial pan-phosphotyrosine antibodies. However, those antibodies were originally generated to recognize many phosphotyrosines in various mammalian proteins and are not optimized for use in bacteria. To address this important limitation, we synthesized 11-mer phospho- and non-phospho-peptides from EPIYA-motifs A, B, and C, and produced three phospho-specific and three non-phospho-specific rabbit polyclonal CagA antibodies. These antibodies specifically recognized the corresponding phosphorylated and non-phosphorylated EPIYA-motifs, while the EPIYA-C antibodies also recognized the related East-Asian EPIYA-D motif. Otherwise, no cross-reactivity of the antibodies among EPIYAs was observed. Western blotting demonstrated that each EPIYA-motif can be predominantly phosphorylated during H. pylori infection. This represents the first complete set of phospho-specific antibodies for an effector protein in bacteria, providing useful tools to gather information for the categorization of CagA phosphorylation, cancer signaling, and gastric disease progression.

• Abl and Src tyrosine kinases
• CagA
• EPIYA motifs
• Helicobacter pylori
• cagPAI
• dotblot
• signaling
• type IV secretion

The gastric pathogen Helicobacter pylori activates the NF-κB pathway in human epithelial cells via the recently discovered α-kinase 1 TRAF-interacting protein with forkhead-associated domain (TIFA) axis. We and others showed that this pathway can be triggered by heptose 1,7-bisphosphate (HBP), an LPS intermediate produced in gram-negative bacteria that represents a new pathogen-associated molecular pattern (PAMP). Here, we report that our attempts to identify HBP in lysates of H. pylori revealed surprisingly low amounts, failing to explain NF-κB activation. Instead, we identified ADP-glycero-β-D-manno-heptose (ADP heptose), a derivative of HBP, as the predominant PAMP in lysates of H. pylori and other gram-negative bacteria. ADP heptose exhibits significantly higher activity than HBP, and cells specifically sensed the presence of the β-form, even when the compound was added extracellularly. The data lead us to conclude that ADP heptose not only constitutes the key PAMP responsible for H. pylori–induced NF-κB activation in epithelial cells, but it acts as a general gram-negative bacterial PAMP.—Pfannkuch, L., Hurwitz, R., Traulsen, J., Sigulla, J., Poeschke, M., Matzner, L., Kosma, P., Schmid, M., Meyer, T. F. ADP heptose, a novel pathogen-associated molecular pattern identified in Helicobacter pylori.

• ALPK1
• LPS
• NF-κB
• PAMP
• TIFA

• FtsZ
• Helicobacter pylori
• Immunoelectron microscopy
• Intrabacterial nanotransportation system
• Urease

• Antigens, Bacterial/metabolism
• Bacterial Proteins/metabolism
• Biological Transport/physiology
• Helicobacter pylori/metabolism
• Humans
• Microscopy, Immunoelectron/methods
• Urease/metabolism

Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa in humans. One of the main virulence factors of H. pylori is the cag pathogenicity island (cagPAI), which encodes a type 4-secretion system (T4SS) and the cytotoxin CagA. Translocation of CagA through the T4SS triggers host-signaling pathways. One of the T4SS proteins is CagL, which is necessary for CagA translocation. CagL is a 26-kDa protein that contains a hypervariable motif, which spans residues 58 to 62. Several polymorphisms in this region have been associated with different disease outcomes, e.g. in Mexico, N58 is associated with a higher risk of gastric cancer. The aim of this work is to analyze the sequence of the hypervariable motif (residues 58 to 62) of clinical isolates from Mexican patients with chronic gastritis, and to correlate these polymorphisms with the vacA genotype.

Of the 164 biopsies analyzed, only 30.5% (50/164) were positive for H. pylori. Thirty-six of the 50 clinical isolates (72%) were cagA positive, and 40 (80%) had the most virulent vacA genotype (s1/m1). Of the cagA positive strains, 94.4% were vacA s1/m1. All the cagA⁺ strains contained the cagL gene. The most prevalent sequence in the polymorphic region (residues 58–62) was DKMGE (75.8%, 25/33), followed by NKMGQ and NEIGQ (6.1%, 2/33), and DEIGQ, NKMGE, DKIGE, and DKIGK (3%, 1/33). Regarding polymorphisms in positions 58 and 59, the most common were D58/K59 (81.8%, 27/33), followed by N58/K59 (9.1%, 3/33), and D58/E59 (3%, 1/33). Only two isolates (6.1%) contained residues N58/E59, which correspond to those found in H. pylori strain ATCC 26695. 92.6% of the clinical isolates having polymorphism D58/K59 had the genotype vacA s1/m1, considered to be the most virulent, while 7.4% had the genotypes vacA s1/m2 and s2/m2.

In Mexican patients, CagL polymorphisms D58, K59, M60, E62, K122, and I134 are more common in patients with chronic gastritis.

• Chronic gastritis
• H. pylori
• Polymorphic region
• cagL polymorphisms

• bacteria
• database
• phosphoproteomics
• proteomics

• ALPK1
• NOD1
• Peptidoglycan
• TIFA
• cagPAI

• Adaptor Proteins, Signal Transducing/metabolism
• Helicobacter Infections/immunology
• Helicobacter Infections/microbiology
• Helicobacter pylori/immunology
• Humans
• Immunity, Innate
• NF-kappa B/metabolism
• Nod1 Signaling Adaptor Protein/metabolism
• Protein Kinases/metabolism
• Signal Transduction