Differences in amino acid frequency in CagA and VacA sequences of Helicobacter pylori distinguish gastric cancer from gastric MALT lymphoma

被引:9
作者
Hashinaga, Masahiko [1 ,2 ]
Suzuki, Rumiko [1 ]
Akada, Junko [1 ]
Matsumoto, Takashi [1 ]
Kido, Yasutoshi [1 ]
Okimoto, Tadayoshi [2 ]
Kodama, Masaaki [2 ,3 ]
Murakami, Kazunari [2 ]
Yamaoka, Yoshio [1 ,4 ,5 ]
机构
[1] Oita Univ, Dept Environm & Prevent Med, Fac Med, 1-1 Idaigaoka,Hasama Machi, Oita 8795593, Japan
[2] Oita Univ, Dept Gastroenterol, Fac Med, 1-1 Idaigaoka,Hasama Machi, Oita 8795593, Japan
[3] Oita Univ, Fac Welf & Hlth Sci, 700 Dannoharu, Oita, Oita 8701192, Japan
[4] Baylor Coll Med, Dept Med Gastroenterol, Houston, TX 77030 USA
[5] Michael E DeBakey VA Med Ctr, Houston, TX USA
基金
日本科学技术振兴机构; 日本学术振兴会; 美国国家卫生研究院;
关键词
Helicobacter pylori; cagA; vacA; Amino acid polymorphism; Next generation sequencing; IV SECRETION SYSTEM; GASTRODUODENAL DISEASES; CYTOTOXIN PRODUCTION; VIRULENCE FACTORS; TISSUE LYMPHOMA; PROTEIN; PHOSPHORYLATION; ASSOCIATION; INFECTION; DIVERSITY;
D O I
10.1186/s13099-016-0137-x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Helicobacter pylori is a pathogenic bacterium that causes various gastrointestinal diseases. The most common gastric malignancies associated with H. pylori are gastric cancer and lymphoma of mucosa associated lymphoid tissue (MALT). Helicobacter pylori virulence genes, namely cagA and vacA, are known to be associated with malignancy development. Conventionally, cagA and vacA were classified by looking at partial sequences of the genes. However, such genotyping has hardly proven useful predicting different risks for gastric cancer or MALT lymphoma. In search of new loci that distinguish these diseases, we investigated the full sequences of cagA and vacA. Results: We compared cagA and vacA sequences of 18 and 12 H. pylori strains obtained, respectively, from patients with gastric cancer and MALT lymphoma in Oita, Japan. Conventional genotyping of cagA and vacA showed no significant difference between the two diseases. We further investigated the full protein sequences of CagA and VacA to identify loci where allele frequency was significantly different between the diseases. We found four such loci on CagA, and three such loci on VacA. We also inspected the corresponding loci on the genes of 22 gastritis strains that potentially lead to gastric cancer or MALT lymphoma in the long run. Significant differences were observed at one CagA locus between gastritis and MALT lymphoma strains, and at one VacA locus between gastritis and gastric cancer strains. Conclusions: We found novel candidate loci in H. pylori virulence genes in association with two different types of gastric malignancies that could not be differentiated by conventional genotyping. Biological connotations of the amino acid polymorphisms merit further study.
引用
收藏
页码:1 / 10
页数:10
相关论文
共 40 条
[1]   The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling [J].
Arnold, K ;
Bordoli, L ;
Kopp, J ;
Schwede, T .
BIOINFORMATICS, 2006, 22 (02) :195-201
[2]   MOSAICISM IN VACUOLATING CYTOTOXIN ALLELES OF HELICOBACTER-PYLORI - ASSOCIATION OF SPECIFIC VACA TYPES WITH CYTOTOXIN PRODUCTION AND PEPTIC-ULCERATION [J].
ATHERTON, JC ;
CAO, P ;
PEEK, RM ;
TUMMURU, MKR ;
BLASER, MJ ;
COVER, TL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (30) :17771-17777
[3]   Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer [J].
Azuma, T ;
Yamazaki, S ;
Yamakawa, A ;
Ohtani, M ;
Muramatsu, A ;
Suto, H ;
Ito, Y ;
Dojo, M ;
Yamazaki, Y ;
Kuriyama, M ;
Keida, Y ;
Higashi, H ;
Hatakeyama, M .
JOURNAL OF INFECTIOUS DISEASES, 2004, 189 (05) :820-827
[4]  
Backert S, 2015, FUTURE MICROBIOL, V10, P955, DOI [10.2217/FMB.15.32, 10.2217/fmb.15.32]
[5]   A Helical RGD Motif Promoting Cell Adhesion: Crystal Structures of the Helicobacter pylori Type IV Secretion System Pilus Protein CagL [J].
Barden, Stephan ;
Lange, Stefanie ;
Tegtmeyer, Nicole ;
Conradi, Jens ;
Sewald, Norbert ;
Backert, Steffen ;
Niemann, Hartmut H. .
STRUCTURE, 2013, 21 (11) :1931-1941
[6]   SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information [J].
Biasini, Marco ;
Bienert, Stefan ;
Waterhouse, Andrew ;
Arnold, Konstantin ;
Studer, Gabriel ;
Schmidt, Tobias ;
Kiefer, Florian ;
Cassarino, Tiziano Gallo ;
Bertoni, Martino ;
Bordoli, Lorenza ;
Schwede, Torsten .
NUCLEIC ACIDS RESEARCH, 2014, 42 (W1) :W252-W258
[7]   Proteome analysis of secreted proteins of the gastric pathogen Helicobacter pylori [J].
Bumann, D ;
Aksu, S ;
Wendland, M ;
Janek, K ;
Zimny-Arndt, U ;
Sabarth, N ;
Meyer, TF ;
Jungblut, PR .
INFECTION AND IMMUNITY, 2002, 70 (07) :3396-3403
[8]   An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA [J].
Conradi, Jens ;
Tegtmeyer, Nicole ;
Wozna, Marta ;
Wissbrock, Marco ;
Michalek, Carmela ;
Gagell, Corinna ;
Cover, Timothy L. ;
Frank, Ronald ;
Sewald, Norbert ;
Backert, Steffen .
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2012, 2 :70
[9]   H. pylori infection and gastric cancer: State of the art (Review) [J].
Conteduca, Vincenza ;
Sansonno, Domenico ;
Lauletta, Gianfranco ;
Russi, Sabino ;
Ingravallo, Giuseppe ;
Dammacco, Franco .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2013, 42 (01) :5-18
[10]   Helicobacter pylori and MALT lymphoma [J].
Farinha, P ;
Gascoyne, RD .
GASTROENTEROLOGY, 2005, 128 (06) :1579-1605