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Genetic diversity and virulence characteristics of Helicobacter pylori isolates in different human ethnic groups

Hanafiah A, Lopes BS

Infect Genet Evol, 2020 Mar;78:104135.
PMID: 31837482 DOI: 10.1016/j.meegid.2019.104135

Helicobacter pylori is the most predominant bacterium in almost 50% of the world's population and colonization causes a persistent inflammatory response leading to chronic gastritis. It shows high genetic diversity and individuals generally harbour a distinct bacterial population. With the advancement of whole-genome sequencing technology, new H. pylori subpopulations have been identified that show admixture between various H. pylori strains. Genotypic variation of H. pylori may be related to the presence of virulence factors among strains and is associated with different outcomes of infection in different individuals. This review summarizes the genetic diversity in H. pylori strain populations and its virulence characteristics responsible for variable outcomes in different ethnic groups.
Fulltext The heterogeneic distribution of Helicobacter pylori cag pathogenicity island reflects different pathologies in multiracial Malaysian population

Hanafiah A, Razak SA, Neoh HM, Zin NM, Lopes BS

Braz J Infect Dis, 2020 11 04;24(6):545-551.
PMID: 33157035 DOI: 10.1016/j.bjid.2020.10.005

BACKGROUND: Helicobacter pylori harbouring cag-pathogenicity island (cagPAI) which encodes type IV secretion system (T4SS) and cagA virulence gene are involved in inflammation of the gastric mucosa. We examined all the 27 cagPAI genes in 88 H. pylori isolates from patients of different ethnicities and examined the association of the intactness of cagPAI region with histopathological scores of the gastric mucosa.
RESULTS: 96.6% (n=85) of H. pylori isolates were cagPAI-positive with 22.4% (19/85) having an intact cagPAI, whereas 77.6% (66/85) had a partial/rearranged cagPAI. The frequency of cag2 and cag14 were found to be significantly higher in H. pylori isolated from Malays, whereas cag4 was predominantly found in Chinese isolates. The cag24 was significantly found in higher proportions in Malay and Indian isolates than in Chinese isolates. The intactness of cagPAI region showed an association with histopathological scores of the gastric mucosa. Significant association was observed between H. pylori harbouring partial cagPAI with higher density of bacteria and neutrophil activity, whereas strains lacking cagPAI were associated with higher inflammatory score.
CONCLUSIONS: The genotypes of H. pylori strains with various cagPAI rearrangement associated with patients' ethnicities and histopathological scores might contribute to the pathogenesis of H. pylori infection in a multi-ethnic population.
Antimicrobial Resistance Mechanisms and Genetic Diversity of Multidrug-Resistant Acinetobacter baumannii Isolated from a Teaching Hospital in Malaysia

Biglari S, Hanafiah A, Mohd Puzi S, Ramli R, Rahman M, Lopes BS

Microb Drug Resist, 2017 Jul;23(5):545-555.
PMID: 27854165 DOI: 10.1089/mdr.2016.0130

Multidrug-resistant (MDR) Acinetobacter baumannii has increasingly emerged as an important nosocomial pathogen. The aim of this study was to determine the resistance profiles and genetic diversity in A. baumannii clinical isolates in a tertiary medical center in Malaysia. The minimum inhibitory concentrations of carbapenems (imipenem and meropenem), cephalosporins (ceftazidime and cefepime), and ciprofloxacin were determined by E-test. PCR and sequencing were carried out for the detection of antibiotic resistance genes and mutations. Clonal relatedness among A. baumannii isolates was determined by REP-PCR. Sequence-based typing of OXA-51 and multilocus sequence typing were performed. One hundred twenty-five of 162 (77.2%) A. baumannii isolates had MDR phenotype. From the 162 A. baumannii isolates, 20 strain types were identified and majority of A. baumannii isolates (66%, n = 107) were classified as strain type 1 and were positive for ISAba1-blaOXA-23and ISAba1-blaADCand had mutations in both gyrA and parC genes at positions, 83 and 80, resulting in serine-to-leucine conversion. REP-PCR analysis showed 129 REP types that generated 31 clones with a 90% similarity cutoff value. OXA-66 variant of the blaOXA-51-likegenes was predominantly detected among our A. baumannii clinical isolates belonging to ST195 (found in six clones: 1, 8, 9, 19, 27, and 30) and ST208 (found in clone 21). The study helps us in understanding the genetic diversity of A. baumannii isolates in our setting and confirms that international clone II is the most widely distributed clone in Universiti Kebangsaan Malaysia Medical Centre, Malaysia.
Fulltext Molecular characterization and prevalence of antibiotic resistance in Helicobacter pylori isolates in Kuala Lumpur, Malaysia

Hanafiah A, Binmaeil H, Raja Ali RA, Mohamed Rose I, Lopes BS

Infect Drug Resist, 2019;12:3051-3061.
PMID: 31632095 DOI: 10.2147/IDR.S219069

Aims and objectives: Helicobacter pylori has been classified as high priority pathogen by the WHO in 2017. The emergence of antibiotic-resistant strains is one of the main causes of treatment failure in H. pylori infection. This study determined and characterized primary and secondary resistances in H. pylori in Malaysia.
Materials and methods: Gastric biopsies from antrum (n=288) and corpus (n=283) were obtained from 288 patients who underwent endoscopy at Universiti Kebangsaan Malaysia Medical Center (UKMMC), Kuala Lumpur, Malaysia. Antibiotic susceptibility to six classes of antibiotics was determined by the E-test. Mutations conferring in resistance in functional genes were identified by PCR and sequencing.
Results: Overall resistance rates to metronidazole, clarithromycin and levofloxacin were 59.3% (35/59), 35.6% (21/59) and 25.4% (15/59), respectively. Secondary isolates showed significantly higher resistance rates to clarithromycin compared to the primary isolates. Mixed infection with susceptible and resistant isolates was observed in 16.2% (6/37) of cases, of which 83.3% (n=5) had infection with the same strain. 41% (18/44) of isolates were resistant to more than one class of antibiotics of which 50% (9/18) were multidrug-resistant, two being primary and seven being secondary isolates. Mutations in rdxA, 23S rRNA and gyrA genes were associated with resistance to metronidazole, clarithromycin and levofloxacin, respectively.
Conclusion: The high level of resistance to metronidazole, clarithromycin and levofloxacin seen in H. pylori isolates in our setting warrants the need for continuous surveillance and highlights caution in use of antibiotics generally used as first-line therapy in H. pylori eradication regimen.