Mobile Genetic Element-driven Genomic Changes in a Community-associated Methicillin-resistant Clone During Its Transmission in a Regional Community Outbreak in Japan

Overview

Journal Microb Genom

Specialties Genetics
Microbiology

Date 2024 Jul 17

PMID 39017043

Authors

Katsuyuki Katahira

Yasuhiro Gotoh

Kentaro Kasama

Dai Yoshimura

Takehiko Itoh

Chieko Shimauchi

Akihiko Tajiri

Tetsuya Hayashi

Affiliations

Soon will be listed here.

Abstract

Community-associated methicillin-resistant (CA-MRSA) infections are now a public health concern in both community and healthcare settings worldwide. We previously identified a suspected case of a maternity clinic-centred outbreak of CA-MRSA skin infection in a regional community in Japan by PFGE-based analysis. In this study, we performed genome sequence-based analyses of 151 CA-MRSA isolates, which included not only outbreak-related isolates that we previously defined based on identical or similar PFGE patterns but also other isolates obtained during the same period in the same region. Our analysis accurately defined 133 isolates as outbreak-related isolates, collectively called the TDC clone. They belonged to a CA-MRSA lineage in clonal complex (CC) 30, known as the South West Pacific (SWP) clone. A high-resolution phylogenetic analysis of these isolates combined with their epidemiological data revealed that the TDC clone was already present and circulating in the region before the outbreak was recognized, and only the isolates belonging to two sublineages (named SL4 and SL5) were directly involved in the outbreak. Long persistence in patients/carriers and frequent intrahousehold transmission of the TDC clone were also revealed by this analysis. Moreover, by systematic analyses of the genome changes that occurred in this CA-MRSA clone during transmission in the community, we revealed that most variations were associated with mobile genetic elements (MGEs). Variant PFGE types were generated by alterations of prophages and genomic islands or insertion sequence (IS)-mediated insertion of a plasmid or a sequence of unknown origin. Dynamic changes in plasmid content, which were linked to changes in antimicrobial resistance profiles in specific isolates, were generated by frequent gain and loss of plasmids, most of which were self-transmissible or mobilizable. The introduction of IS by a plasmid (named pTDC02) into sublineage SL5 led to SL5-specific amplification of IS and amplified IS copies were involved in some of the structural changes of chromosomes and plasmids and generated variations in the repertoire of virulence-related genes in limited isolates. These data revealed how CA-MRSA genomes change during transmission in the community and how MGEs are involved in this process.

Citing Articles

Clinical Features and Antibiotic Susceptibility of -Infected Dermatoses.

Koumaki D, Maraki S, Evangelou G, Koumaki V, Gregoriou S, Kouloumvakou S J Clin Med. 2025; 14(4).

PMID: 40004615 PMC: 11856689. DOI: 10.3390/jcm14041084.

References

Firth N, Jensen S, Kwong S, Skurray R, Ramsay J . Staphylococcal Plasmids, Transposable and Integrative Elements. Microbiol Spectr. 2018; 6(6). PMC: 11633639. DOI: 10.1128/microbiolspec.GPP3-0030-2018. View

Letunic I, Bork P . Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res. 2016; 44(W1):W242-5. PMC: 4987883. DOI: 10.1093/nar/gkw290. View

Holden M, Hsu L, Kurt K, Weinert L, Mather A, Harris S . A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic. Genome Res. 2013; 23(4):653-64. PMC: 3613582. DOI: 10.1101/gr.147710.112. View

Tong S, Holden M, Nickerson E, Cooper B, Koser C, Cori A . Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting. Genome Res. 2014; 25(1):111-8. PMC: 4317166. DOI: 10.1101/gr.174730.114. View

Jamrozy D, Coll F, Mather A, Harris S, Harrison E, MacGowan A . Evolution of mobile genetic element composition in an epidemic methicillin-resistant Staphylococcus aureus: temporal changes correlated with frequent loss and gain events. BMC Genomics. 2017; 18(1):684. PMC: 5584012. DOI: 10.1186/s12864-017-4065-z. View

Kozlov A, Darriba D, Flouri T, Morel B, Stamatakis A . RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference. Bioinformatics. 2019; 35(21):4453-4455. PMC: 6821337. DOI: 10.1093/bioinformatics/btz305. View

OBrien F, Yui Eto K, Murphy R, Fairhurst H, Coombs G, Grubb W . Origin-of-transfer sequences facilitate mobilisation of non-conjugative antimicrobial-resistance plasmids in Staphylococcus aureus. Nucleic Acids Res. 2015; 43(16):7971-83. PMC: 4652767. DOI: 10.1093/nar/gkv755. View

Carattoli A, Zankari E, Garcia-Fernandez A, Larsen M, Lund O, Villa L . In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother. 2014; 58(7):3895-903. PMC: 4068535. DOI: 10.1128/AAC.02412-14. View

Ji G, Silver S . Regulation and expression of the arsenic resistance operon from Staphylococcus aureus plasmid pI258. J Bacteriol. 1992; 174(11):3684-94. PMC: 206058. DOI: 10.1128/jb.174.11.3684-3694.1992. View

10.

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

11.

Kaya H, Hasman H, Larsen J, Stegger M, Johannesen T, Allesoe R . SCCFinder, a Web-Based Tool for Typing of Staphylococcal Cassette Chromosome in Using Whole-Genome Sequence Data. mSphere. 2018; 3(1). PMC: 5812897. DOI: 10.1128/mSphere.00612-17. View

12.

Knox J, Uhlemann A, Lowy F . Staphylococcus aureus infections: transmission within households and the community. Trends Microbiol. 2015; 23(7):437-44. PMC: 4490959. DOI: 10.1016/j.tim.2015.03.007. View

13.

Walker T, Ip C, Harrell R, Evans J, Kapatai G, Dedicoat M . Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis. 2012; 13(2):137-46. PMC: 3556524. DOI: 10.1016/S1473-3099(12)70277-3. View

14.

Jolley K, Maiden M . BIGSdb: Scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics. 2010; 11:595. PMC: 3004885. DOI: 10.1186/1471-2105-11-595. View

15.

McAdam P, Templeton K, Edwards G, Holden M, Feil E, Aanensen D . Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus. Proc Natl Acad Sci U S A. 2012; 109(23):9107-12. PMC: 3384211. DOI: 10.1073/pnas.1202869109. View

16.

Ramsay J, Kwong S, Murphy R, Yui Eto K, Price K, Nguyen Q . An updated view of plasmid conjugation and mobilization in Staphylococcus. Mob Genet Elements. 2016; 6(4):e1208317. PMC: 4993578. DOI: 10.1080/2159256X.2016.1208317. View

17.

Inouye M, Dashnow H, Raven L, Schultz M, Pope B, Tomita T . SRST2: Rapid genomic surveillance for public health and hospital microbiology labs. Genome Med. 2014; 6(11):90. PMC: 4237778. DOI: 10.1186/s13073-014-0090-6. View

18.

. Classification of staphylococcal cassette chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements. Antimicrob Agents Chemother. 2009; 53(12):4961-7. PMC: 2786320. DOI: 10.1128/AAC.00579-09. View

19.

Kajitani R, Yoshimura D, Ogura Y, Gotoh Y, Hayashi T, Itoh T . Platanus_B: an accurate de novo assembler for bacterial genomes using an iterative error-removal process. DNA Res. 2020; 27(3). PMC: 7433917. DOI: 10.1093/dnares/dsaa014. View

20.

Robinson D, Kearns A, Holmes A, Morrison D, Grundmann H, Edwards G . Re-emergence of early pandemic Staphylococcus aureus as a community-acquired meticillin-resistant clone. Lancet. 2005; 365(9466):1256-8. DOI: 10.1016/S0140-6736(05)74814-5. View