Drivers of methicillin-resistant Staphylococcus aureus (MRSA) lineage replacement in China.
Anti-Bacterial Agents
/ pharmacology
Biofilms
/ growth & development
China
/ epidemiology
Evolution, Molecular
Genome, Bacterial
Genomics
Genotype
Hospitals
Humans
Methicillin-Resistant Staphylococcus aureus
/ classification
Microbial Sensitivity Tests
Molecular Epidemiology
Multilocus Sequence Typing
Prevalence
Staphylococcal Infections
/ epidemiology
Virulence
/ genetics
Virulence Factors
/ genetics
Whole Genome Sequencing
Lineage replacement
Methicillin-resistant Staphylococcus aureus (MRSA)
Molecular evolution
Phylogeny
Phylogeography
Virulence
Journal
Genome medicine
ISSN: 1756-994X
Titre abrégé: Genome Med
Pays: England
ID NLM: 101475844
Informations de publication
Date de publication:
28 10 2021
28 10 2021
Historique:
received:
23
03
2021
accepted:
17
10
2021
entrez:
29
10
2021
pubmed:
30
10
2021
medline:
22
2
2022
Statut:
epublish
Résumé
Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing the previously dominant healthcare-associated (HA-MRSA) ST239. We previously showed that ST59 isolates tend to have a competitive advantage in growth experiments against ST239. However, the underlying genomic and phenotypic drivers of this replacement event are unclear. Here, we investigated the replacement of ST239 using whole-genome sequencing data from 204 ST239 and ST59 isolates collected in Chinese hospitals between 1994 and 2016. We reconstructed the evolutionary history of each ST and considered two non-mutually exclusive hypotheses for ST59 replacing ST239: antimicrobial resistance (AMR) profile and/or ability to colonise and persist in the environment through biofilm formation. We also investigated the differences in cytolytic activity, linked to higher virulence, between STs. We performed an association study using the presence and absence of accessory virulence genes. ST59 isolates carried fewer AMR genes than ST239 and showed no evidence of evolving towards higher AMR. Biofilm production was marginally higher in ST59 overall, though this effect was not consistent across sub-lineages so is unlikely to be a sole driver of replacement. Consistent with previous observations of higher virulence in CA-MRSA STs, we observed that ST59 isolates exhibit significantly higher cytolytic activity than ST239 isolates, despite carrying on average fewer putative virulence genes. Our association study identified the chemotaxis inhibitory protein (chp) as a strong candidate for involvement in the increased virulence potential of ST59. We experimentally validated the role of chp in increasing the virulence potential of ST59 by creating Δchp knockout mutants, confirming that ST59 can carry chp without a measurable impact on fitness. Our results suggest that the ongoing replacement of ST239 by ST59 in China is not associated to higher AMR carriage or biofilm production. However, the increase in ST59 prevalence is concerning since it is linked to a higher potential for virulence, aided by the carriage of the chp gene.
Sections du résumé
BACKGROUND
Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing the previously dominant healthcare-associated (HA-MRSA) ST239. We previously showed that ST59 isolates tend to have a competitive advantage in growth experiments against ST239. However, the underlying genomic and phenotypic drivers of this replacement event are unclear.
METHODS
Here, we investigated the replacement of ST239 using whole-genome sequencing data from 204 ST239 and ST59 isolates collected in Chinese hospitals between 1994 and 2016. We reconstructed the evolutionary history of each ST and considered two non-mutually exclusive hypotheses for ST59 replacing ST239: antimicrobial resistance (AMR) profile and/or ability to colonise and persist in the environment through biofilm formation. We also investigated the differences in cytolytic activity, linked to higher virulence, between STs. We performed an association study using the presence and absence of accessory virulence genes.
RESULTS
ST59 isolates carried fewer AMR genes than ST239 and showed no evidence of evolving towards higher AMR. Biofilm production was marginally higher in ST59 overall, though this effect was not consistent across sub-lineages so is unlikely to be a sole driver of replacement. Consistent with previous observations of higher virulence in CA-MRSA STs, we observed that ST59 isolates exhibit significantly higher cytolytic activity than ST239 isolates, despite carrying on average fewer putative virulence genes. Our association study identified the chemotaxis inhibitory protein (chp) as a strong candidate for involvement in the increased virulence potential of ST59. We experimentally validated the role of chp in increasing the virulence potential of ST59 by creating Δchp knockout mutants, confirming that ST59 can carry chp without a measurable impact on fitness.
CONCLUSIONS
Our results suggest that the ongoing replacement of ST239 by ST59 in China is not associated to higher AMR carriage or biofilm production. However, the increase in ST59 prevalence is concerning since it is linked to a higher potential for virulence, aided by the carriage of the chp gene.
Identifiants
pubmed: 34711267
doi: 10.1186/s13073-021-00992-x
pii: 10.1186/s13073-021-00992-x
pmc: PMC8555231
doi:
Substances chimiques
Anti-Bacterial Agents
0
Virulence Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
171Subventions
Organisme : Wellcome Trust
ID : 215239/Z/19/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V033417/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N006364/2
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 220422/Z/20/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R01356X/1
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
Références
J Antimicrob Chemother. 2012 Nov;67(11):2640-4
pubmed: 22782487
BMC Genomics. 2017 Sep 4;18(1):684
pubmed: 28870171
Infect Immun. 2015 May;83(5):2168-74
pubmed: 25776748
Clin Microbiol Rev. 2010 Jul;23(3):616-87
pubmed: 20610826
J Antimicrob Chemother. 2011 May;66 Suppl 4:iv43-iv48
pubmed: 21521706
J Antimicrob Chemother. 2009 Sep;64(3):441-6
pubmed: 19608582
Nat Rev Microbiol. 2015 Sep;13(9):529-43
pubmed: 26272408
Int J Antimicrob Agents. 2011 Jul;38(1):2-8
pubmed: 21397461
J Hosp Infect. 2009 Mar;71(3):245-55
pubmed: 19157644
J Clin Microbiol. 2004 May;42(5):2080-4
pubmed: 15131173
Mol Syst Biol. 2011 Oct 11;7:539
pubmed: 21988835
Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9107-12
pubmed: 22586109
Int J Antimicrob Agents. 2013 Sep;42(3):211-9
pubmed: 23871455
Nucleic Acids Res. 2011 Jul;39(Web Server issue):W347-52
pubmed: 21672955
Genome Res. 2013 Apr;23(4):653-64
pubmed: 23299977
J Antimicrob Chemother. 2012 Oct;67(10):2514-22
pubmed: 22761331
Trends Microbiol. 2014 Jan;22(1):42-7
pubmed: 24331435
mBio. 2015 Mar 03;6(2):e00080
pubmed: 25736880
Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):E10596-E10604
pubmed: 29158405
Clin Microbiol Infect. 2022 Jan;28(1):85-92
pubmed: 34022399
Front Microbiol. 2018 Feb 27;9:332
pubmed: 29535697
Mol Biol Evol. 2011 May;28(5):1593-603
pubmed: 21112962
Antimicrob Agents Chemother. 2007 Apr;51(4):1497-9
pubmed: 17283194
Bioinformatics. 2014 May 1;30(9):1312-3
pubmed: 24451623
J Infect Dis. 2020 Mar 16;221(Suppl 2):S220-S228
pubmed: 32176793
J Clin Microbiol. 2007 Sep;45(9):2881-8
pubmed: 17626175
Eur J Clin Microbiol Infect Dis. 2016 Aug;35(8):1285-95
pubmed: 27177754
Antimicrob Agents Chemother. 2000 Jun;44(6):1549-55
pubmed: 10817707
PLoS Pathog. 2010 Apr 08;6(4):e1000855
pubmed: 20386717
Int J Infect Dis. 2014 Dec;29:84-90
pubmed: 25449241
BMC Evol Biol. 2017 Feb 6;17(1):42
pubmed: 28166715
Genome Biol. 2016 Jul 26;17(1):160
pubmed: 27459968
Nat Rev Dis Primers. 2018 May 31;4:18033
pubmed: 29849094
Trends Microbiol. 2018 Dec;26(12):1035-1048
pubmed: 30193960
PLoS Comput Biol. 2014 Apr 10;10(4):e1003537
pubmed: 24722319
N Engl J Med. 1998 Aug 20;339(8):520-32
pubmed: 9709046
J Med Microbiol. 2018 Mar;67(3):408-414
pubmed: 29458545
Curr Biol. 2019 Oct 21;29(20):R1094-R1103
pubmed: 31639358
Infect Immun. 2012 Oct;80(10):3438-53
pubmed: 22825451
Eur J Clin Microbiol Infect Dis. 2010 Aug;29(8):977-85
pubmed: 20509037
Nat Rev Microbiol. 2009 Sep;7(9):629-41
pubmed: 19680247
J Clin Microbiol. 2013 Nov;51(11):3638-44
pubmed: 23985906
Lancet Infect Dis. 2013 Aug;13(8):698-708
pubmed: 23827369
Clin Microbiol Infect. 2007 Oct;13(10):971-9
pubmed: 17697003
Emerg Microbes Infect. 2021 Dec;10(1):109-122
pubmed: 33355507
Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1327-32
pubmed: 18216255
Chem Sci. 2018 Feb 22;9(12):3248-3253
pubmed: 29780457
J Antimicrob Chemother. 2001 Jul;48(1):143-4
pubmed: 11418528
PLoS One. 2019 Oct 24;14(10):e0223599
pubmed: 31647842
J Clin Microbiol. 2008 Apr;46(4):1520-2
pubmed: 18234867
Annu Rev Microbiol. 2010;64:143-62
pubmed: 20825344
J Comput Biol. 2012 May;19(5):455-77
pubmed: 22506599
Antimicrob Agents Chemother. 2006 Mar;50(3):1001-12
pubmed: 16495263
Proc Natl Acad Sci U S A. 2002 May 28;99(11):7687-92
pubmed: 12032344
Lancet Infect Dis. 2018 Mar;18(3):318-327
pubmed: 29276051
Trends Microbiol. 2004 Aug;12(8):378-85
pubmed: 15276614
Nucleic Acids Res. 2018 Dec 14;46(22):e134
pubmed: 30184106
Nat Rev Microbiol. 2019 Apr;17(4):203-218
pubmed: 30737488
J Bacteriol. 2008 Feb;190(4):1276-83
pubmed: 18083809
Infect Dis Clin North Am. 2009 Mar;23(1):17-34
pubmed: 19135914
mBio. 2021 Dec 21;12(6):e0216821
pubmed: 34903061
Virus Evol. 2016 Apr 09;2(1):vew007
pubmed: 27774300
PLoS Comput Biol. 2015 Feb 12;11(2):e1004041
pubmed: 25675341
JAMA. 2007 Oct 17;298(15):1763-71
pubmed: 17940231
Evol Appl. 2015 Mar;8(3):284-95
pubmed: 25861386
Genome Biol. 2020 Jul 22;21(1):180
pubmed: 32698896
Antimicrob Agents Chemother. 2009 Feb;53(2):512-8
pubmed: 19029328
J Clin Microbiol. 2005 Jun;43(6):2923-5
pubmed: 15956420
Sci Rep. 2016 Jun 14;6:27899
pubmed: 27296890
Front Microbiol. 2020 Mar 17;11:422
pubmed: 32256477
World J Pediatr. 2020 Jun;16(3):284-292
pubmed: 31620982
mBio. 2016 May 05;7(3):
pubmed: 27150362
J Clin Microbiol. 2014 May;52(5):1501-10
pubmed: 24574290
Nucleic Acids Res. 2019 Jan 8;47(D1):D687-D692
pubmed: 30395255
J Clin Microbiol. 2017 Sep;55(9):2808-2816
pubmed: 28679522
Genome Biol. 2015 Apr 23;16:81
pubmed: 25903077
Infect Control Hosp Epidemiol. 2014 Mar;35(3):285-92
pubmed: 24521595
Cell Microbiol. 2006 Aug;8(8):1282-93
pubmed: 16882032
Front Microbiol. 2019 Feb 20;10:304
pubmed: 30842766
Bioinformatics. 2014 Jul 15;30(14):2068-9
pubmed: 24642063
Genome Med. 2021 Oct 28;13(1):171
pubmed: 34711267
PLoS One. 2013 Sep 05;8(9):e63210
pubmed: 24039691
Science. 2010 Jan 22;327(5964):469-74
pubmed: 20093474
Mol Biol Evol. 2012 Sep;29(9):2157-67
pubmed: 22403239
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D32-6
pubmed: 16381877
Clin Microbiol Rev. 2019 May 29;32(3):
pubmed: 31142498