Restricted accessResearch articleFirst published online 2024-02
Molecular Epidemiological Characterization of Methicillin-Resistant Staphylococcus aureus from Bloodstream Infections in Northern Japan: Increasing Trend of CC1 and Identification of ST8-SCC mec IVa USA300-Like Isolate Lacking Arginine Catabolic Mobile Element
Methicillin-resistant Staphylococcus aureus (MRSA) is a major infectious disease pathogen, and its molecular epidemiological profile has been changing. In this study, a total of 279 MRSA isolates were collected from patients with bloodstream infection (BSI) in Hokkaido, northern main island of Japan, for a 2-year period from August 2019 to July 2021. CC5 (ST5/ST764)-MRSA-IIa (SCCmec-IIa) (47%, n = 132) and CC1 (ST1/ST2725/ST2764)-MRSA-IVa (42%, n = 116) were found to be major lineages, with CC8-MRSA-IVa being lower prevalence (5%, n = 13). CC1-MRSA-IVa showed a relatively increased proportion compared with our previous study (22%, 2017–2019). Seven isolates with SCCmec IVa (2.5%) were positive for Panton–Valentine leukocidin genes on ΦSa2usa and belonged to ST8/spa-t008/agr-I/coa-IIIa, showing genetic features of the USA300 clone. Among these isolates, six isolates harbored arginine catabolic mobile element (ACME) type I typical to the USA300 clone, while it was not detected in an isolate (strain R3-8). Whole genomic analysis of strain R3-8 revealed that its chromosome was highly similar to the USA300 strain TCH1516, but lacked ACME, carrying a plasmid genetically close to that of USA300 strains. The present study revealed increasing trend of CC1-MRSA-IV and occurrence of a novel variant of the USA300 clone among MRSA from BSI in northern Japan.
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References
1.
LauplandKB, ChurchDL. Population-based epidemiology and microbiology of community-onset bloodstream infections. Clin Microbiol Rev, 2014; 27(4):647–664; doi: 10.1128/CMR.00002-14
2.
LauplandKB, LyytikäinenO, SøgaardM, et al.The changing epidemiology of Staphylococcus aureus bloodstream infection: A multinational population-based surveillance study. Clin Microbiol Infect, 2013; 19(5):465–471; doi: 10.1111/j.1469-0691.2012.03903.x
3.
BaiAD, LoCKL, KomorowskiAS, et al.Staphylococcus aureus bacteraemia mortality: A systematic review and meta-analysis. Clin Microbiol Infect, 2022; 28(8):1076–1084; doi: 10.1016/j.cmi.2022.03.015
4.
ShojiT, MutoR, FukudaH, et al.Cost and healthcare utilization of methicillin-resistant Staphylococcus aureus bacteremia estimated from linked antimicrobial resistance surveillance and hospital claims data in Japan. Antimicrob Steward Healthc Epidemiol, 2022; 2(1):e147; doi: 10.1017/ash.2022.280
WangW, HuY, BakerM, et al.Novel SCCmec type XV (7A) and two pseudo-SCCmec variants in foodborne MRSA in China. J Antimicrob Chemother, 2022; 77(4):903–909; doi: 10.1093/jac/dkab500
7.
ChambersHF, DeleoFR. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol, 2009; 7(9):629–641; doi: 10.1038/nrmicro2200
8.
DavidMZ, DaumRS. Community-associated methicillin-resistant Staphylococcus aureus: Epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev, 2010; 23:616–687; doi: 10.1128/CMR.00081-09
9.
MediavillaJR, ChenL, MathemaB, et al.Global epidemiology of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA). Curr Opin Microbiol, 2012; 15(5):588–595; doi: 10.1016/j.mib.2012.08.003
10.
LeeAS, de LencastreH, GarauJ, et al.Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Primers, 2018; 4:18033; doi: 10.1038/nrdp.2018.33
ChoiSH, LeeJ, JungJ, et al.A longitudinal study of adult patients with Staphylococcus aureus bacteremia over 11 years in Korea. J Korean Med Sci, 2021; 36(16):e104; doi: 10.3346/jkms.2021.36.e104
13.
YangE, KimE, ChungH, et al.Changing characteristics of S. aureus bacteremia caused by PVL-negative, MRSA strain over 11 years. Sci Rep, 2021; 11(1):15677; doi: 10.1038/s41598-021-95115-2
14.
ChenPY, ChuangYC, WangJT, et al.Sequence type 8 as an emerging clone of methicillin-resistant Staphylococcus aureus causing bloodstream infections in Taiwan. Emerg Microbes Infect, 2021; 10(1):1908–1918; doi: 10.1080/22221751.2021.1981158
15.
HuangYC, ChenCJ. USA300 (sequence type 8) has become a major clone of methicillin-resistant Staphylococcus aureus in northern Taiwan. Int J Antimicrob Agents, 2022; 59(3):106534; doi: 10.1016/j.ijantimicag.2022.106534
16.
NiekWK, TehCSJ, IdrisN, et al.Methicillin-resistant Staphylococcus aureus bacteraemia, 2003–2015: Comparative evaluation of changing trends in molecular epidemiology and clinical outcomes of infections. Infect Genet Evol, 2020; 85:104567; doi: 10.1016/j.meegid.2020.104567
17.
DotelR, O'SullivanMVN, DavisJS, et al.Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolates in New South Wales, Australia, 2012–2017. Infect Dis Health, 2019; 24(3):134–140; doi: 10.1016/j.idh.2019.04.002
18.
Vázquez-SánchezDA, GrilloS, Carrera-SalinasA, et al.Molecular epidemiology, antimicrobial susceptibility, and clinical features of methicillin-resistant Staphylococcus aureus bloodstream infections over 30 years in Barcelona, Spain (1990–2019). Microorganisms, 2022; 10(12):2401; doi: 10.3390/microorganisms10122401
19.
SaugetM, BouillerK, RichardM, et al.Increasing incidence of bloodstream infections due to Staphylococcus aureus clonal complex 398 in a French hospital between 2010 and 2017. Eur J Clin Microbiol Infect Dis, 2019; 38(11):2127–2132; doi: 10.1007/s10096-019-03653-5
20.
SouliM, RuffinF, ChoiSH, et al.Changing characteristics of Staphylococcus aureus bacteremia: Results from a 21-year, prospective, longitudinal study. Clin Infect Dis, 2019; 69(11):1868–1877; doi: 10.1093/cid/ciz112
Nimmo GR. USA300 abroad: Global spread of a virulent strain of community-associated methicillin-resistant Staphylococcus aureus. Clin Microbiol Infect, 2012; 18(8):725–734. doi: 10.1111/j.1469-0691.2012.03822.x
23.
DiepBA, GillSR, ChangRF, et al.Complete genome sequence of USA300, an epidemic clone of community-acquired methicillin-resistant Staphylococcus aureus. Lancet, 2006; 367(9512):731–739; doi: 10.1016/S0140-6736(06)68231-7
24.
Ahmad-MansourN, LoubetP, PougetC, et al.Staphylococcus aureus toxins: An update on their pathogenic properties and potential treatments. Toxins (Basel), 2021; 13(10):677; doi: 10.3390/toxins13100677
25.
CheungGYC, BaeJS, OttoM. Pathogenicity and virulence of Staphylococcus aureus. Virulence, 2021; 12(1):547–569; doi: 10.1080/21505594.2021.1878688
26.
YamaguchiT, NakamuraI, SatoT, et al.Changes in the genotypic characteristics of community-acquired methicillin-resistant Staphylococcus aureus collected in 244 medical facilities in Japan between 2010 and 2018: A nationwide surveillance. Microbiol Spectr, 2022; 10(4):e0227221; doi: 10.1128/spectrum.02272-21
27.
TakadamaS, NakaminamiH, SatoA, et al.Dissemination of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus USA300 clone in multiple hospitals in Tokyo, Japan. Clin Microbiol Infect, 2018; 24(11):1211.e1–e1211.e7; doi: 10.1016/j.cmi.2018.02.012
28.
ShimizuM, MiharaT, OharaJ. Relationship between mortality and molecular epidemiology of methicillin-resistant Staphylococcus aureus bacteremia. PLoS One, 2022; 17(7):e0271115; doi: 10.1371/journal.pone.0271115
29.
HamadaM, YamaguchiT, SatoA, et al.Increased incidence and plasma-biofilm formation ability of SCCmec type IV Methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients with bacteremia. Front Cell Infect Microbiol, 2021; 11:602833; doi: 10.3389/fcimb.2021.602833
30.
KakuN, SasakiD, OtaK, et al.Changing molecular epidemiology and characteristics of MRSA isolated from bloodstream infections: Nationwide surveillance in Japan in 2019. J Antimicrob Chemother, 2022; 77(8):2130–2141. doi: 10.1093/jac/dkac154
31.
AungMS, KawaguchiyaM, UrushibaraN, et al.Molecular characterization of methicillin-resistant Staphylococcus aureus from outpatients in Northern Japan: Increasing tendency of ST5/ST764 MRSA-IIa with arginine catabolic mobile element. Microb Drug Resist, 2017; 23(5):616–625; doi: 10.1089/mdr.2016.0176
32.
AungMS, UrushibaraN, KawaguchiyaM, et al.Clonal diversity and genetic characteristics of methicillin-resistant Staphylococcus aureus isolates from a tertiary care hospital in Japan. Microb Drug Resist, 2019; 25(8):1164–1175; doi: 10.1089/mdr.2018.0468
33.
AungMS, UrushibaraN, KawaguchiyaM, et al.Clonal diversity of methicillin-resistant Staphylococcus aureus (MRSA) from bloodstream infections in northern Japan: Identification of spermidine N-acetyltransferase gene (speG) in staphylococcal cassette chromosomes (SCCs) associated with type II and IV SCCmec. J Glob Antimicrob Resist, 2021; 24:207–214; doi: 10.1016/j.jgar.2020.12.008
34.
Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing. Thirty-Two. Informational Supplement, M100-S32, Wayne, PA, USA; 2022.
35.
The European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint Tables for Interpretation of MICs and Zone Diameters, Version 12.0; 2022. Available from: www.eucast.org [Last accessed: December13, 2022].
36.
WatanabeA, YanagiharaK, MatsumotoT, et al.Nationwide surveillance of bacterial respiratory pathogens conducted by the Surveillance Committee of Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Clinical Microbiology in 2009: General view of the pathogens' antibacterial susceptibility. J Infect Chemother, 2012; 18(5):609–620; doi: 10.1007/s10156-012-0434-3
37.
ZhangK, McClureJA, ElsayedS, et al.Novel multiplex PCR assay for simultaneous identification of community-associated methicillin-resistant Staphylococcus aureus strains USA300 and USA400 and detection of mecA and Panton-Valentine Leukocidin genes, with discrimination of Staphylococcus aureus from coagulase-negative staphylococci. J Clin Microbiol, 2008; 46(3):1118–1122; doi: 10.1128/JCM.01309-07
38.
ZhangDF, XuX, SongQ, et al.Identification of Staphylococcus argenteus in Eastern China based on a nonribosomal peptide synthetase (NRPS) gene. Future Microbiol, 2016; 11:1113–1121; doi: 10.2217/fmb-2016-0017
39.
KondoY, ItoT, MaXX, et al.Combination of multiplex PCRs for staphylococcal cassette chromosome mec type assignment: Rapid identification system for mec, ccr, and major differences in junkyard regions. Antimicrob Agents Chemother, 2007; 51(1):264–274; doi: 10.1128/AAC.00165-06
40.
MilheiriçoC, OliveiraDC, de LencastreH. Multiplex PCR strategy for subtyping the staphylococcal cassette chromosome mec type IV in methicillin-resistant Staphylococcus aureus: ‘SCCmec IV multiplex’. J Antimicrob Chemother, 2007; 60(1):42–48; doi: 10.1093/jac/dkm112
41.
AungMS, SanT, UrushibaraN, et al.Molecular characterization of methicillin-susceptible and -resistant Staphylococcus aureus harboring Panton-Valentine Leukocidin-encoding bacteriophages in a tertiary care hospital in Myanmar. Microb Drug Resist, 2020; 26(4):360–367; doi: 10.1089/mdr.2019.0208
42.
ShopsinB, GomezM, MontgomerySO, et al.Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains. J Clin Microbiol, 1999; 37(11):3556–3563; doi: 10.1128/JCM.37.11.3556-3563.1999
43.
AungMS, SanT, SanN, et al.Molecular characterization of Staphylococcus argenteus in Myanmar: Identification of novel genotypes/clusters in staphylocoagulase, protein A, alpha-haemolysin and other virulence factors. J Med Microbiol, 2019; 68(1):95–104; doi: 10.1099/jmm.0.000869
44.
EnrightMC, DayNP, DaviesCE, et al.Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol, 2000; 38(3):1008–1015; doi: 10.1128/JCM.38.3.1008-1015.2000
45.
AungMS, UrushibaraN, KawaguchiyaM, et al.Prevalence and genetic diversity of staphylococcal enterotoxin (-like) genes sey, selw, selx, selz, sel26 and sel27 in community-acquired methicillin-resistant Staphylococcus aureus. Toxins (Basel), 2020; 12(5):347; doi: 10.3390/toxins12050347
46.
AungMS, UrushibaraN, KawaguchiyaM, et al.Distribution of virulence factors and resistance determinants in three genotypes of Staphylococcus argenteus clinical isolates in Japan. Pathogens, 2021; 10(2):163; doi: 10.3390/pathogens10020163
47.
AungMS, UrushibaraN, KawaguchiyaM, et al.Antimicrobial resistance, virulence factors, and genotypes of Enterococcus faecalis and Enterococcus faecium clinical isolates in Northern Japan: Identification of optrA in ST480 E. faecalis. Antibiotics (Basel), 2023; 12(1):108; doi: 10.3390/antibiotics12010108
48.
SmythDS, RobinsonDA. Integrative and sequence characteristics of a novel genetic element, ICE6013, in Staphylococcus aureus. J Bacteriol, 2009; 191(19):5964–5975; doi: 10.1128/JB.00352-09
49.
HighlanderSK, HulténKG, QinX, et al.Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus. BMC Microbiol, 2007; 7:99; doi: 10.1186/1471-2180-7-99
50.
OguraK, KajiD, SasakiM, et al.Predominance of ST8 and CC1/spa-t1784 methicillin-resistant Staphylococcus aureus isolates in Japan and their genomic characteristics. J Glob Antimicrob Resist, 2022; 28:195–202; doi: 10.1016/j.jgar.2022.01.011
51.
GubbayJB, GosbellIB, BarbagiannakosT, et al.Clinical features, epidemiology, antimicrobial resistance, and exotoxin genes (including that of Panton-Valentine Leukocidin) of gentamicin-susceptible methicillin-resistant Staphylococcus aureus (GS-MRSA) isolated at a paediatric teaching hospital in New South Wales, Australia. Pathology, 2008; 40(1):64–71; doi: 10.1080/00313020701716276
52.
MoneckeS, CoombsG, ShoreAC. A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus. PLoS One, 2011; 6(4):e17936; doi: 10.1371/journal.pone.0017936
53.
GuY, FujitomoY, OhmagariN. Outcomes and future prospect of Japan's National Action Plan on antimicrobial resistance (2016–2020). Antibiotics (Basel), 2021; 10(11):1293; doi: 10.3390/antibiotics10111293
54.
TkadlecJ, CapekV, BrajerovaM, et al.The molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in the Czech Republic. J Antimicrob Chemother, 2021; 76(1):55–64. doi: 10.1093/jac/dkaa404
55.
TkadlecJ, LeAV, BrajerovaM, et al.Epidemiology of methicillin-resistant Staphylococcus aureus in Slovakia, 2020—Emergence of an epidemic USA300 clone in community and hospitals. Microbiol Spectr, 2023; 11(4):e0126423. doi: 10.1128/spectrum.01264-23
56.
YabeS, TakanoT, HiguchiW, et al.Spread of the community-acquired methicillin-resistant Staphylococcus aureus USA300 clone among family members in Japan. J Infect Chemother, 2010; 16(5):372–374; doi: 10.1007/s10156-010-0087-z
57.
TakadamaS, NakaminamiH, TakiiT, et al.Identification and detection of USA300 methicillin-resistant Staphylococcus aureus clones with a partial deletion in the ccrB2 gene on the type IV SCCmec element. Diagn Microbiol Infect Dis, 2019; 94(1):86–87; doi: 10.1016/j.diagmicrobio.2018.11.016
58.
ShinoharaK, UeharaY, TeruyaK, et al.Emergence of community-associated methicillin-resistant Staphylococcus aureus ΨUSA300 among Japanese people with HIV, resulted from stepwise mutations in 2010s. Sci Rep, 2023; 13(1):8322; doi: 10.1038/s41598-023-35171-y
HaradaN, TogashiA, AungMS, et al.Acute osteomyelitis/septic pulmonary embolism associated with familial infections caused by PVL-positive ST6562 MRSA-IVa, a presumptive variant of USA300 clone. IJID Regions, 2023; 8:16–18; doi: 10.1016/j.ijregi.2023.05.006
61.
HiroseM, AungMS, FukudaA, et al.Antimicrobial resistance and molecular epidemiological characteristics of methicillin-resistant and susceptible staphylococcal isolates from oral cavity of dental patients and staff in northern Japan. Antibiotics (Basel), 2021; 10(11):1316; doi: 10.3390/antibiotics10111316
62.
HiroseM, AungMS, FujitaY, et al.Genetic characterization of Staphylococcus aureus, Staphylococcus argenteus, and coagulase-negative staphylococci colonizing oral cavity and hand of healthy adults in northern Japan. Pathogens, 2022; 11(8):849; doi: 10.3390/pathogens11080849
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