Elucidation of host diversity of the VanD-carrying genomic islands in enterococci and anaerobes

Author:

Hashimoto Yusuke1,Hisatsune Junzo234,Suzuki Masato4ORCID,Kurushima Jun1,Nomura Takahiro1,Hirakawa Hidetada1,Kojima Naoko5,Ono Yuichi5,Hasegawa Yutaka5,Tanimoto Koichi6,Sugai Motoyuki234,Tomita Haruyoshi16

Affiliation:

1. Department of Bacteriology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

2. Department of Antimicrobial Resistance, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan

3. Project Research Center for Nosocomial Infectious Diseases, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan

4. Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002, Japan

5. Infection Control Team, Gunma Prefectural Cardiovascular Center, 3-12 Ko Kameizumi-machi, Maebashi, Gunma 371-0004, Japan

6. Laboratory of Bacterial Drug Resistance, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

Abstract

Abstract Background VanD is a rare type of vancomycin resistance worldwide. However, the host diversity of the vanD gene cluster and the structural similarity of their genomic islands are not well understood. Methods Three VanD-type Enterococcus faecium strains (AA620, AA622 and AA624) isolated from a Japanese patient who underwent vancomycin treatment in 2017 were analysed. This study utilized WGS analysis to characterize the three VanD-type E. faecium strains and describes the diversity of hosts possessing VanD-carrying genomic islands. Results The three isolates exhibited variable MICs of vancomycin. In the relatively vancomycin-resistant AA620, mutations were identified in vanSD and ddl. The strains AA622 and AA624 had intact ddl and harboured two vanD gene clusters. qRT-PCR results revealed the ddl mutation to be a factor affecting the high vancomycin resistance range of AA620. WGS data showed the 155 kb and 185 kb genomic islands harbouring the vanD gene cluster inserted in the coding region of the lysS gene, located in the chromosome in AA620 and AA622/624, respectively. Comparing the VanD-carrying genomic islands to available sequences of other enterococci and enteric anaerobes revealed how the genomic islands of these organisms isolated worldwide shared similar core genes and backbones. These anaerobes belonged to various genera within the order Eubacteriales. The phylogenetic cluster of the genomic island core genome alignment did not correlate with the host-species lineage, indicating horizontal gene transfer in the gut microbiota. Conclusions By horizontal gene transfer, various bacteria forming the gut microbiota maintain VanD-carrying genomic islands.

Funder

Japanese Ministry of Health, Labor and Welfare

Research Program on ensuring Food Safety

Japan Agency for Medical Research and Development

Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan

Grant-in-Aid for Early-Career Scientists

Publisher

Oxford University Press (OUP)

Subject

General Medicine

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