Genotypic Profiling and Clinical Impact of Helicobacter pylori Virulence Genes ( GLM , HPU , V acA , C agA , and I ceA ) in Gastroduodenal Diseases among Libyan Patients — Oak Academic Publishing
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Genotypic Profiling and Clinical Impact of Helicobacter pylori Virulence Genes ( GLM , HPU , V acA , C agA , and I ceA ) in Gastroduodenal Diseases among Libyan Patients
Department of Life Sciences/Microbiology Programme, School of Basic Sciences, Libyan Academy of Postgraduate Studies, Benghazi, Libya
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Department of Microbiology, Faculty of Science, University of Benghazi, Benghazi, Libya
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Department of Microbiology, Faculty of Science, University of Benghazi, Benghazi, Libya
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Department of Molecular Diagnosis, Faculty of Biomedical Sciences, University of Benghazi, Benghazi, Libya
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Libyan International Medical University, Benghazi, Libya
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Benghazi Center for Infectious Diseases and Immunology, Benghazi, Libya
Helicobacter pylori infection represents a widespread chronic condition with varying prevalence influenced by race, ethnicity, and geography. The severity of H. pylori -associated diseases is determined by an array of virulence factors. Although extensive studies have been conducted globally, data on the distribution of Helicobacter pylori virulence genes in Libya remain limited, constraining insights into the pathogenicity of local strains and hindering the development of targeted interventions. This study aimed to evaluate the prevalence of H. pylori infection, characterize essential virulence genes [ v acA variants (s1/s2, m1/m2), c agA , and i ceA 1], and examine their association with gastroduodenal diseases among Libyan patients. Gastric biopsies from 144 participants were analyzed using polymerase chain reaction (PCR) assays, and risk factor data were collected via questionnaires. H. pylori was detected in 63.2% of samples by PCR. The v acA gene was present in 84.6% of cases, c agA in 58.2%, and i ceA 1 in 29.7%. Among v acA variants, s1 allele was most common (53.2%), followed by m1 (42.9%), m2 (37.7%), and s2 (13%) alleles. Significant associations were identified between specific virulence genes and the development of gastroduodenal diseases, highlighting their role in pathogenicity. This investigation is one of Libya’s first comprehensive assessments of H. pylori virulence factors, addressing a critical epidemiological gap. The high prevalence of virulence genes suggests their potential as disease biomarkers. These findings contribute to a deeper understanding of H. pylori pathogenicity within the Libyan population and establish a basis for future clinical interventions and public health strategies to manage and prevent H. pylori -associated diseases in Libya and comparable regions.
Essawi, T., Hammoudeh, W., Sabri, I., Sweidan, W. and Farraj, M.A. (2013) Determination of Helicobacter pylori Virulence Genes in Gastric Biopsies by PCR. ISRN Gastroenterology , 2013, Article ID: 606258. https://doi.org/10.1155/2013/606258
Palframan, S.L., Kwok, T. and Gabriel, K. (2012) Vacuolating Cytotoxin a (VacA), a Key Toxin for Helicobacter pylori Pathogenesis. Frontiers in Cellular and Infection Microbiology , 2, Article 92. https://doi.org/10.3389/fcimb.2012.00092
Šebunova, N., Štšepetova, J., Sillakivi, T. and Mändar, R. (2018) The Prevalence of Helicobacter pylori in Estonian Bariatric Surgery Patients. International Journal of Molecular Sciences , 19, Article 338. https://doi.org/10.3390/ijms19020338
Quaglia, N.C. and Dambrosio, A. (2018) Helicobacter pylori : A Foodborne Pathogen? World Journal of Gastroenterology , 24, 3472-3487. https://doi.org/10.3748/wjg.v24.i31.3472
Amieva, M.R. and El-Omar, E.M. (2008) Host-Bacterial Interactions in Helicobacter pylori Infection. Gastroenterology , 134, 306-323. https://doi.org/10.1053/j.gastro.2007.11.009
Chen, Y., Mo, X., Huang, G., Huang, Y., Xiao, J., Zhao, L., et al . (2016) Gene Polymorphisms of Pathogenic Helicobacter pylori in Patients with Different Types of Gastrointestinal Diseases. World Journal of Gastroenterology , 22, 9718-9726. https://doi.org/10.3748/wjg.v22.i44.9718
Cavalcante, M.Q.D.F., Silva, C.I.S., Braga-Neto, M.B., Fialho, A.B.C., Nunes Fialho, A., Barbosa, A.M.C., et al . (2012) Helicobacter pylori vacA and cagA Genotypes in Patients from Northeastern Brazil with Upper Gastrointestinal Diseases. Memórias do Instituto Oswaldo Cruz , 107, 561-563. https://doi.org/10.1590/s0074-02762012000400021
Lina, T.T. (2014) Immune Evasion Strategies Used by Helicobacter pylori . World Journal of Gastroenterology , 20, 12753-12766. https://doi.org/10.3748/wjg.v20.i36.12753
Kabamba, E.T., Tuan, V.P. and Yamaoka, Y. (2018) Genetic Populations and Virulence Factors of Helicobacter pylori . Infection , Genetics and Evolution , 60, 109-116. https://doi.org/10.1016/j.meegid.2018.02.022
Abu-Taleb, A.M.F., Abdelattef, R.S., Abdel-Hady, A.A., Omran, F.H., El-Korashi, L.A., Abdel-Aziz El-Hady, H., et al . (2018) Prevalence of Helicobacter pylori cagA and iceA Genes and Their Association with Gastrointestinal Diseases. International Journal of Microbiology , 2018, Article ID: 4809093. https://doi.org/10.1155/2018/4809093
Talebi Bezmin Abadi, A. (2017) Strategies Used by Helicobacter pylori to Establish Persistent Infection. World Journal of Gastroenterology , 23, 2870-2882. https://doi.org/10.3748/wjg.v23.i16.2870
Logan, R. (1996) Adherence of Helicobacter pylori . Alimentary Pharmacology & Therapeutics , 10, 3-15. https://doi.org/10.1046/j.1365-2036.1996.22164001.x
Aspholm, M., Kalia, A., Ruhl, S., Schedin, S., Arnqvist, A., Lindén, S., et al . (2006) Helicobacter pylori Adhesion to Carbohydrates. Methods in Enzymology , 417, 293-339. https://doi.org/10.1016/s0076-6879(06)17020-2
Zheng, P. and Jones, N.L. (2003) Helicobacter pylori Strains Expressing the Vacuolating Cytotoxin Interrupt Phagosome Maturation in Macrophages by Recruiting and Retaining TACO (Coronin 1) Protein. Cellular Microbiology , 5, 25-40. https://doi.org/10.1046/j.1462-5822.2003.00250.x
Wroblewski, L.E., Peek, R.M. and Wilson, K.T. (2010) Helicobacter pylori and Gastric Cancer: Factors That Modulate Disease Risk. Clinical Microbiology Reviews , 23, 713-739. https://doi.org/10.1128/cmr.00011-10
Akeel, M., Shehata, A., Elhafey, A., Elmakki, E., Aboshouk, T., Ageely, H., et al . (2019) Helicobacter pylori v ac A , c ag A and i ce A Genotypes in Dyspeptic Patients from Southwestern Region, Saudi Arabia: Distribution and Association with Clinical Outcomes and Histopathological Changes. BMC Gastroenterology , 19, Article No. 16. https://doi.org/10.1186/s12876-019-0934-z
Sarma, A., Saikia, L., Bhuyan, R.K. and Hussain, M.E. (2017) Molecular Identification and Detection of Virulent Factors in Helicobacter pylori from Gastric Biopsy Samples of Patients Attended at Assam Medical College and Hospital, Dibrugarh, Assam, India. Indian Journal of Medical Microbiology , 35, 600-603. https://doi.org/10.4103/ijmm.ijmm_17_232
Sabbagh, P., Javanian, M., Koppolu, V., Vasigala, V.R. and Ebrahimpour, S. (2019) Helicobacter pylori Infection in Children: An Overview of Diagnostic Methods. European Journal of Clinical Microbiology & Infectious Diseases , 38, 1035-1045. https://doi.org/10.1007/s10096-019-03502-5
Wang, Y. (2015) Diagnosis of Helicobacter pylori Infection: Current Options and Developments. World Journal of Gastroenterology , 21, 11221-11235. https://doi.org/10.3748/wjg.v21.i40.11221
Hatakeyama, M. (2009) Helicobacter pylori and Gastric Carcinogenesis. Journal of Gastroenterology , 44, 239-248. https://doi.org/10.1007/s00535-009-0014-1
Miernyk, K., Morris, J., Bruden, D., McMahon, B., Hurlburt, D., Sacco, F., et al . (2011) Characterization of Helicobacter pylori c ag A and vacA Genotypes among Alaskans and Their Correlation with Clinical Disease. Journal of Clinical Microbiology , 49, 3114-3121. https://doi.org/10.1128/jcm.00469-11
Sayed Zaki, M.E., Elewa, A., Abdelwahab Ali, M. and Shehta, A. (2016) Study of Virulence Genes Cag A and Vac A in Helicobacter pylori Isolated from Mansoura University Hospital Patients by Multiplex PCR. International Journal of Current Microbiology and Applied Sciences , 5, 154-160. https://doi.org/10.20546/ijcmas.2016.502.018
Nimri, L.F., Matalka, I., Bani-Hani, K.E. and Ibrahim, M. (2006) Helicobacter pylori Genotypes Identified in Gastric Biopsy Specimens from Jordanian Patients. BMC Gastroenterology , 6, Article No. 27. https://doi.org/10.1186/1471-230x-6-27
Bolek, B.K., Salih, B.A. and Sander, E. (2007) Genotyping of Helicobacter pylori Strains from Gastric Biopsies by Multiplex Polymerase Chain Reaction. How Advantageous Is It? Diagnostic Microbiology and Infectious Disease , 58, 67-70. https://doi.org/10.1016/j.diagmicrobio.2006.12.001
Momenah, A.M. and Tayeb, M.T. (2007) Helicobacter pylori cagA and iceA Geno-types Status and Risk of Peptic Ulcer in Saudi Patients. Saudi Medical Journal , 28, 382-385.
Marie, M.A.M. (2012) Relationship between Helicobacter pylori Virulence Genes and Clinical Outcomes in Saudi Patients. Journal of Korean Medical Science , 27, 190-193. https://doi.org/10.3346/jkms.2012.27.2.190
Qabandi, A.A., Mustafa, A.S., Siddique, I., Khajah, A.K., Madda, J.P. and Junaid, T.A. (2005) Distribution of vacA and cagA Genotypes of Helicobacter pylori in Kuwait. Acta Tropica , 93, 283-288. https://doi.org/10.1016/j.actatropica.2005.01.004
van Doorn, L., Figueiredo, C., Sanna, R., Plaisier, A., Schneeberger, P., de Boer, W., et al . (1998) Clinical Relevance of the cagA , vacA , and iceA Status of Helicobacter pylori . Gastroenterology , 115, 58-66. https://doi.org/10.1016/s0016-5085(98)70365-8
Villllalobos, L.B., Cavazza, M.E. and Ortiz-Princz, D. (2015) Detection of cagA Gene and Typing vacA Gene of Helicobacter pylori in Biopsies of Patients with Gastric Symptoms in Cumana, Sucre State, Venezuela. SABER . Revista Multidisciplinaria del Consejo de Investigación de la Universidad de Oriente , 27, 430-440.
Hatakeyama, M. (2017) Structure and Function of Helicobacter pylori c ag A , the First-Identified Bacterial Protein Involved in Human Cancer. Proceedings of the Japan Academy , Series B , 93, 196-219. https://doi.org/10.2183/pjab.93.013
Tohidpour, A. (2016) CagA-Mediated Pathogenesis of Helicobacter pylori . Microbial Pathogenesis , 93, 44-55. https://doi.org/10.1016/j.micpath.2016.01.005
Sarıbaş, Z., Demir, H., Simşek, H., Ozen, H. and Akyön, Y. (2010) Detection of cagA Prevalence in Clinical Isolates of Helicobacter pylori . Mikrobiyoloji Bulteni , 44, 461-465.
Hooi, J.K.Y., Lai, W.Y., Ng, W.K., Suen, M.M.Y., Underwood, F.E., Tanyingoh, D., et al . (2017) Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology , 153, 420-429. https://doi.org/10.1053/j.gastro.2017.04.022
Falsafi, T., Khani, A., Mahjoub, F., Asgarani, E. and Sotoudeh, N. (2015) Analysis of Vaca/cagA Genotypes/Status in Helicobacter pylori Isolates from Iranian Children and Their Association with Clinical Outcome. Turkish Journal of Medical Sciences , 45, 170-177. https://doi.org/10.3906/sag-1311-2
Kadi, R.H., Halawani, E.M. and Abdelkader, H.S. (2014) Prevalence of H . pylori Strains Harbouring cagA and iceA Virulence Genes in Saudi Patients with Gastritis and Peptic Ulcer Disease. Microbiology Discovery , 2, Article 2. https://doi.org/10.7243/2052-6180-2-2
Shiota, S., Watada, M., Matsunari, O., Iwatani, S., Suzuki, R. and Yamaoka, Y. (2012) Helicobacter pylori iceA, Clinical Outcomes, and Correlation with cagA: A Meta-Analysis. PLOS ONE , 7, e30354. https://doi.org/10.1371/journal.pone.0030354
Ciftci, I.H., Uslan, I., Dilek, F.H., Aşık, G., Ozgür, M.A. and Dilek, O.N. (2011) [In-vestigation of Helicobacter pylori iceA1 and iceA2 Genes in Patients with Chronic Gastritis and Gastric Cancer]. Mikrobiyoloji bulteni , 45, 228-233.
Wei, G., Chen, J., Liu, A., Zhang, M., Liu, X., Liu, D., et al . (2012) Prevalence of Helicobacter pylori vacA, cagA and iceA Genotypes and Correlation with Clinical Outcome. Experimental and Therapeutic Medicine , 4, 1039-1044. https://doi.org/10.3892/etm.2012.704
Ben Mansour, K., Fendri, C., Zribi, M., Masmoudi, A., Labbene, M., Fillali, A., et al . (2010) Prevalence of Helicobacter pylori vacA , cagA , iceA and oipA Genotypes in Tunisian Patients. Annals of Clinical Microbiology and Antimicrobials , 9, Article No. 10. https://doi.org/10.1186/1476-0711-9-10
Nogueira, C., Figueiredo, C., Carneiro, F., Taveira Gomes, A., Barreira, R., Figueira, P., et al . (2001) Helicobacter pylori Genotypes May Determine Gastric Histopathology. The American Journal of Pathology , 158, 647-654. https://doi.org/10.1016/s0002-9440(10)64006-0
Park, J.Y., Forman, D., Waskito, L.A., Yamaoka, Y. and Crabtree, J.E. (2018) Epidemiology of Helicobacter pylori and cagA -Positive Infections and Global Variations in Gastric Cancer. Toxins , 10, Article 163. https://doi.org/10.3390/toxins10040163
Zambon, C. (2003) Helicobacter pylori babA2, cagA, and s1 vacA Genes Work Synergistically in Causing Intestinal Metaplasia. Journal of Clinical Pathology , 56, 287-291. https://doi.org/10.1136/jcp.56.4.287
Malfertheiner, P., Chan, F.K. and McColl, K.E. (2009) Peptic Ulcer Disease. The Lancet , 374, 1449-1461. https://doi.org/10.1016/s0140-6736(09)60938-7
Tomb, J., White, O., Kerlavage, A.R., Clayton, R.A., Sutton, G.G., Fleischmann, R.D., et al . (1997) Erratum: The Complete Genome Sequence of the Gastric Pathogen Helicobacter pylori . Nature , 389, 412-412. https://doi.org/10.1038/38792