J Korean Med Sci.  2014 Mar;29(3):328-333. 10.3346/jkms.2014.29.3.328.

Recent Trends of Antigenic Variation in Bordetella pertussis Isolates in Korea

Affiliations
  • 1Division of Bacterial Respiratory Infections, Korea National Institute of Health, Osong, Korea. jungsangoun@gmail.com
  • 2Pathogen Resource TF, Korea National Institute of Health, Osong, Korea.
  • 3Division of Antimicrobial Resistance, Korea National Institute of Health, Osong, Korea.

Abstract

Pertussis is a representative vaccine-preventable disease. However, there have been recent outbreaks in countries where even higher vaccination against the disease. One reason is the emergence of antigenic variants, which are different to vaccine type. In Korea, reported cases have rapidly increased since 2009. Therefore, we analyzed genotype of strains isolated in 2011-2012 by multilocus sequence typing method. As expected, the genotype profiles of tested genes dramatically changed. The major sequence type changed from ST1 to ST2, and new sequence type (ST8) appeared. In the minimum spanning tree, recent isolates belonging to the ACC-I-ST3 subgroup were detected that were composed of ST2, ST3, and ST6. In particular, the ST2 frequency increased to 81%. The novel ST8 was linked to the increased frequency of ST2. In addition, toxic strains carrying the ptxP3 promoter type were confirmed. This ptxP3 type emerged from 2009 and its frequency had increased to 100% in 2012. Based on these results, it can be inferred that the genotypic changes in the currently circulating strains are strongly associated with the recent increasing of pertussis in Korea. Therefore, the surveillance system should be strengthened, and genetic characterization of the isolates should be expanded to the whole genome sequence level.

Keyword

Pertussis Vaccine; Bordetella pertussis; Antigenic Variation; Multilocus Sequence Typing; Pertussis Toxin; Minimum Spanning Tree

MeSH Terms

*Antigenic Variation
Antigens/*genetics/immunology/metabolism
Bacterial Proteins/genetics/metabolism
Bordetella pertussis/*genetics/isolation & purification/*metabolism
Genes, Bacterial
Genotype
Humans
Pertussis Toxin/genetics/metabolism
Promoter Regions, Genetic
Republic of Korea
Sequence Analysis, DNA
Whooping Cough/immunology/*microbiology/pathology
Antigens
Bacterial Proteins
Pertussis Toxin

Figure

  • Fig. 1 Annually reported pertussis cases in Korea. The number of pertussis cases was obtained from the disease web statistics system (http://stat.cdc.go.kr) established by the Korea Centers for Disease Control and Prevention. Data of the global incidence were obtained from the WHO Disease Incidence database. The analyzed period was 13 yr from 2000 to 2012, which was divided into 2 stages according to the number of reported cases in Korea. The stable stage is the period that showed a relatively narrow fluctuation range in the difference of annually reported cases. The increasing stage is the period that showed a continuous increase in number of reported cases.

  • Fig. 2 Sequence type change in the isolates of 2011-2012. Sequence type changes observed for the isolates of 2011-2012 are compared to the results of our previous report (14).

  • Fig. 3 Minimum spanning tree by MLST profiles. A minimum spanning tree was generated with the PHYLOViZ program. All the sequence types observed in the Korean isolates were linked together by a single locus variation and composed of a single clonal complex, except ST4 (singleton). The results of "based upon related sequence types (BURST)" analysis reveal two antigenic clonal complex (ACC) subgroups (ACC I and ACC II).

  • Fig. 4 Minimum spanning tree by MLST profiles according to the isolation year. A minimum spanning tree was reconstituted according to the isolation year. The increase in the number of pertussis cases (Fig. 1) is associated with expansion of the ACC I-ST3 subgroup since 2009. In particular, the ST3-ST2-ST8 lineage is expanded in the increasing stage (2009-2011). Compared with 2009 isolates, there are few isolates belonging to the ACC II-ST1 subgroup.

  • Fig. 5 Minimum spanning tree by MLST profiles according to the variant type of pertussis toxin promoter. A minimum spanning tree was reconstituted according to the variant type of the pertussis toxin promoter. The pertussis toxin promoter (ptxP) 3 type is observed only in 3 sequence types (ST3, ST2, and ST8). The presence of the ptxP3 type might be dependent on the isolation year because ST2 and ST8 have recently expanded.


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