Silence as a way of niche adaptation: mecC-MRSA with variations in the accessory gene regulator (agr) functionality express kaleidoscopic phenotypes.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 09 2020
08 09 2020
Historique:
received:
10
12
2019
accepted:
19
08
2020
entrez:
9
9
2020
pubmed:
10
9
2020
medline:
27
3
2021
Statut:
epublish
Résumé
Functionality of the accessory gene regulator (agr) quorum sensing system is an important factor promoting either acute or chronic infections by the notorious opportunistic human and veterinary pathogen Staphylococcus aureus. Spontaneous alterations of the agr system are known to frequently occur in human healthcare-associated S. aureus lineages. However, data on agr integrity and function are sparse regarding other major clonal lineages. Here we report on the agr system functionality and activity level in mecC-carrying methicillin resistant S. aureus (MRSA) of various animal origins (n = 33) obtained in Europe as well as in closely related human isolates (n = 12). Whole genome analysis assigned all isolates to four clonal complexes (CC) with distinct agr types (CC599 agr I, CC49 agr II, CC130 agr III and CC1943 agr IV). Agr functionality was assessed by a combination of phenotypic assays and proteome analysis. In each CC, isolates with varying agr activity levels were detected, including the presence of completely non-functional variants. Genomic comparison of the agr I-IV encoding regions associated these phenotypic differences with variations in the agrA and agrC genes. The genomic changes were detected independently in divergent lineages, suggesting that agr variation might foster viability and adaptation of emerging MRSA lineages to distinct ecological niches.
Identifiants
pubmed: 32901059
doi: 10.1038/s41598-020-71640-4
pii: 10.1038/s41598-020-71640-4
pmc: PMC7479134
doi:
Substances chimiques
Agr protein, Staphylococcus aureus
0
Bacterial Proteins
0
Hemolysin Proteins
0
Proteome
0
Trans-Activators
0
Virulence Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14787Références
Walther, B. et al. Equine methicillin-resistant sequence type 398 Staphylococcus aureus (MRSA) harbor mobile genetic elements promoting host adaptation. Front. Microbiol. 9, 2516. https://doi.org/10.3389/fmicb.2018.02516 (2018).
doi: 10.3389/fmicb.2018.02516
pubmed: 30405574
pmcid: 6207647
Lowy, F. D. Staphylococcus aureus infections. N. Engl. J. Med. 339, 520–532. https://doi.org/10.1056/nejm199808203390806 (1998).
doi: 10.1056/nejm199808203390806
pubmed: 9709046
Kriegeskorte, A. & Peters, G. Horizontal gene transfer boosts MRSA spreading. Nat. Med. 18, 662–663. https://doi.org/10.1038/nm.2765 (2012).
doi: 10.1038/nm.2765
pubmed: 22561821
Peacock, S. J. & Paterson, G. K. Mechanisms of methicillin resistance in Staphylococcus aureus. Annu. Rev. Biochem. 84, 577–601. https://doi.org/10.1146/annurev-biochem-060614-034516 (2015).
doi: 10.1146/annurev-biochem-060614-034516
pubmed: 26034890
Garcia-Alvarez, L. et al. Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study. Lancet Infect. Dis. 11, 595–603. https://doi.org/10.1016/s1473-3099(11)70126-8 (2011).
doi: 10.1016/s1473-3099(11)70126-8
pubmed: 21641281
pmcid: 3829197
Baig, S. et al. Novel SCCmec type XIII (9A) identified in an ST152 methicillin-resistant Staphylococcus aureus. Infect. Genet. Evol. 61, 74–76. https://doi.org/10.1016/j.meegid.2018.03.013 (2018).
doi: 10.1016/j.meegid.2018.03.013
pubmed: 29567305
Kerschner, H., Harrison, E. M., Hartl, R., Holmes, M. A. & Apfalter, P. First report of mecC MRSA in human samples from Austria: molecular characteristics and clinical data. New Microb. New Infect. 3, 4–9. https://doi.org/10.1016/j.nmni.2014.11.001 (2015).
doi: 10.1016/j.nmni.2014.11.001
Paterson, G. K., Harrison, E. M. & Holmes, M. A. The emergence of mecC methicillin-resistant Staphylococcus aureus. Trends Microbiol. 22, 42–47. https://doi.org/10.1016/j.tim.2013.11.003 (2014).
doi: 10.1016/j.tim.2013.11.003
pubmed: 24331435
pmcid: 3989053
Cuny, C., Layer, F., Strommenger, B. & Witte, W. Rare occurrence of methicillin-resistant Staphylococcus aureus CC130 with a novel mecA homologue in humans in Germany. PLoS ONE 6, e24360. https://doi.org/10.1371/journal.pone.0024360 (2011).
doi: 10.1371/journal.pone.0024360
pubmed: 21931689
pmcid: 3169590
Ford, B. A. mecC-harboring methicillin-resistant Staphylococcus aureus: hiding in plain sight. J. Clin. Microbiol. 5, 6. https://doi.org/10.1128/jcm.01549-17 (2018).
doi: 10.1128/jcm.01549-17
Kil, E. H., Heymann, W. R. & Weinberg, J. M. Methicillin-resistant Staphylococcus aureus: an update for the dermatologist, part 4: additional therapeutic considerations. Cutis 81, 343–347 (2008).
pubmed: 18491483
Shore, A. C. et al. Detection of staphylococcal cassette chromosome mec type XI carrying highly divergent mecA, mecI, mecR1, blaZ, and ccr genes in human clinical isolates of clonal complex 130 methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 55, 3765–3773. https://doi.org/10.1128/aac.00187-11 (2011).
doi: 10.1128/aac.00187-11
pubmed: 21636525
pmcid: 3147645
Worthing, K. A. et al. Isolation of mecC MRSA in Australia. J. Antimicrob. Chemother. 71, 2348–2349. https://doi.org/10.1093/jac/dkw138 (2016).
doi: 10.1093/jac/dkw138
pubmed: 27118772
Walther, B. et al. MRSA variant in companion animals. Emerg. Infect. Dis. 18, 2017–2020. https://doi.org/10.3201/eid1812.120238 (2012).
doi: 10.3201/eid1812.120238
pubmed: 23171478
pmcid: 3557870
Loncaric, I. et al. Characterization of methicillin-resistant Staphylococcus spp. carrying the mecC gene, isolated from wildlife. J. Antimicrob. Chemother. 68, 2222–2225. https://doi.org/10.1093/jac/dkt186 (2013).
doi: 10.1093/jac/dkt186
pubmed: 23674764
Garcia-Garrote, F. et al. Methicillin-resistant Staphylococcus aureus carrying the mecC gene: emergence in Spain and report of a fatal case of bacteraemia. J. Antimicrob. Chemother. 69, 45–50. https://doi.org/10.1093/jac/dkt327 (2014).
doi: 10.1093/jac/dkt327
pubmed: 23975743
Mekonnen, S. A. et al. Metabolic niche adaptation of community- and hospital-associated methicillin-resistant Staphylococcus aureus. J. Proteom. 193, 154–161. https://doi.org/10.1016/j.jprot.2018.10.005 (2019).
doi: 10.1016/j.jprot.2018.10.005
Paharik, A. E. & Horswill, A. R. The Staphylococcal biofilm: adhesins, regulation, and host response. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.VMBF-0022-2015 (2016).
doi: 10.1128/microbiolspec.VMBF-0022-2015
pubmed: 27227309
pmcid: 4887152
Hammer, N. D. & Skaar, E. P. Molecular mechanisms of Staphylococcus aureus iron acquisition. Annu. Rev. Microbiol. 65, 129–147. https://doi.org/10.1146/annurev-micro-090110-102851 (2011).
doi: 10.1146/annurev-micro-090110-102851
pubmed: 21639791
Lerat, E. & Ochman, H. Recognizing the pseudogenes in bacterial genomes. Nucl. Acids Res. 33, 3125–3132. https://doi.org/10.1093/nar/gki631 (2005).
doi: 10.1093/nar/gki631
pubmed: 15933207
Mcgavin, M., Arsic, B. & Nickerson, N. Evolutionary blueprint for host- and niche-adaptation in Staphylococcus aureus clonal complex CC30. Front. Cell. Infect. Microbiol. https://doi.org/10.3389/fcimb.2012.00048 (2012).
doi: 10.3389/fcimb.2012.00048
pubmed: 22919657
pmcid: 3417565
Tavares, A. et al. Insights into alpha-hemolysin (Hla) evolution and expression among Staphylococcus aureus clones with hospital and community origin. PLoS ONE 9, e98634. https://doi.org/10.1371/journal.pone.0098634 (2014).
doi: 10.1371/journal.pone.0098634
pubmed: 25033196
pmcid: 4102472
Yoong, P. & Torres, V. J. Counter inhibition between leukotoxins attenuates Staphylococcus aureus virulence. Nat. Commun. 6, 8125. https://doi.org/10.1038/ncomms9125 (2015).
doi: 10.1038/ncomms9125
pubmed: 26330208
pmcid: 4562310
Chadha, A. D. et al. Host response to Staphylococcus aureus cytotoxins in children with cystic fibrosis. J. Cyst. Fibros. Off. J. Eur. Cyst. Fibros. Soc. 15, 597–604. https://doi.org/10.1016/j.jcf.2015.12.023 (2016).
doi: 10.1016/j.jcf.2015.12.023
Benson, M. A. et al. Evolution of hypervirulence by a MRSA clone through acquisition of a transposable element. Mol. Microbiol. 93, 664–681. https://doi.org/10.1111/mmi.12682 (2014).
doi: 10.1111/mmi.12682
pubmed: 24962815
pmcid: 4127135
Busche, T. et al. Comparative secretome analyses of human and zoonotic Staphylococcus aureus Isolates CC8, CC22, and CC398. Mol. Cell. Proteom. MCP 17, 2412–2433. https://doi.org/10.1074/mcp.RA118.001036 (2018).
doi: 10.1074/mcp.RA118.001036
Richardson, E. J. et al. Gene exchange drives the ecological success of a multi-host bacterial pathogen. Nat. Ecol. Evol. 2, 1468–1478. https://doi.org/10.1038/s41559-018-0617-0 (2018).
doi: 10.1038/s41559-018-0617-0
pubmed: 30038246
Walther, B. et al. Comparative molecular analysis substantiates zoonotic potential of equine methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 47, 704–710. https://doi.org/10.1128/jcm.01626-08 (2009).
doi: 10.1128/jcm.01626-08
pubmed: 19109463
Wang, B. & Muir, T. W. Regulation of virulence in Staphylococcus aureus: molecular mechanisms and remaining puzzles. Cell Chem. Biol. 23, 214–224. https://doi.org/10.1016/j.chembiol.2016.01.004 (2016).
doi: 10.1016/j.chembiol.2016.01.004
pubmed: 26971873
pmcid: 4847544
Jenul, C. & Horswill, A. R. Regulation of Staphylococcus aureus virulence. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.GPP3-0031-2018 (2018).
doi: 10.1128/microbiolspec.GPP3-0031-2018
pubmed: 30953424
pmcid: 6452892
Cheung, A. L. et al. Diminished virulence of a sar-/agr-mutant of Staphylococcus aureus in the rabbit model of endocarditis. J. Clin. Investig. 94, 1815–1822. https://doi.org/10.1172/jci117530 (1994).
doi: 10.1172/jci117530
pubmed: 7962526
Kobayashi, S. D. et al. Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection. J. Infect. Dis. 204, 937–941. https://doi.org/10.1093/infdis/jir441 (2011).
doi: 10.1093/infdis/jir441
pubmed: 21849291
pmcid: 3156927
Abdelnour, A., Arvidson, S., Bremell, T., Rydén, C. & Tarkowski, A. The accessory gene regulator (agr) controls Staphylococcus aureus virulence in a murine arthritis model. Infect. Immun. 61, 3879–3885 (1993).
doi: 10.1128/IAI.61.9.3879-3885.1993
Fowler, V. G. Jr. et al. Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein. J. Infect. Dis. 190, 1140–1149. https://doi.org/10.1086/423145 (2004).
doi: 10.1086/423145
pubmed: 15319865
Traber, K. E. et al. agr function in clinical Staphylococcus aureus isolates. Microbiology (Reading, England) 154, 2265–2274. https://doi.org/10.1099/mic.0.2007/011874-0 (2008).
doi: 10.1099/mic.0.2007/011874-0
Schweizer, M. L. et al. Increased mortality with accessory gene regulator (agr) dysfunction in Staphylococcus aureus among bacteremic patients. Antimicrob. Agents Chemother. 55, 1082–1087. https://doi.org/10.1128/aac.00918-10 (2011).
doi: 10.1128/aac.00918-10
pubmed: 21173172
Painter, K. L., Krishna, A., Wigneshweraraj, S. & Edwards, A. M. What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?. Trends Microbiol. 22, 676–685. https://doi.org/10.1016/j.tim.2014.09.002 (2014).
doi: 10.1016/j.tim.2014.09.002
pubmed: 25300477
Yang, X. et al. Accessory gene regulator (agr) dysfunction was unusual in Staphylococcus aureus isolated from Chinese children. BMC Microbiol. 19, 95. https://doi.org/10.1186/s12866-019-1465-z (2019).
doi: 10.1186/s12866-019-1465-z
pubmed: 31088356
pmcid: 6518674
He, L. et al. Resistance to leukocytes ties benefits of quorum sensing dysfunctionality to biofilm infection. Nat. Microbiol. 4, 1114–1119. https://doi.org/10.1038/s41564-019-0413-x (2019).
doi: 10.1038/s41564-019-0413-x
pubmed: 6588452
pmcid: 6588452
Altman, D. R. et al. Genome plasticity of agr-defective Staphylococcus aureus during clinical infection. Infect. Immun. https://doi.org/10.1128/iai.00331-18 (2018).
doi: 10.1128/iai.00331-18
pubmed: 30242013
pmcid: 6204747
Goerke, C. et al. Direct quantitative transcript analysis of the agr regulon of Staphylococcus aureus during human infection in comparison to the expression profile in vitro. Infect. Immun. 68, 1304–1311. https://doi.org/10.1128/iai.68.3.1304-1311.2000 (2000).
doi: 10.1128/iai.68.3.1304-1311.2000
pubmed: 10678942
pmcid: 97283
Suligoy, C. M. et al. Mutation of Agr is associated with the adaptation of Staphylococcus aureus to the host during chronic osteomyelitis. Front. Cell. Infect. Microbiol. 8, 18. https://doi.org/10.3389/fcimb.2018.00018 (2018).
doi: 10.3389/fcimb.2018.00018
pubmed: 29456969
pmcid: 5801681
Le, K. Y. & Otto, M. Quorum-sensing regulation in staphylococci—an overview. Front. Microbiol. 6, 1174. https://doi.org/10.3389/fmicb.2015.01174 (2015).
doi: 10.3389/fmicb.2015.01174
pubmed: 26579084
pmcid: 4621875
Reynolds, J. & Wigneshweraraj, S. Molecular insights into the control of transcription initiation at the Staphylococcus aureus agr operon. J. Mol. Biol. 412, 862–881. https://doi.org/10.1016/j.jmb.2011.06.018 (2011).
doi: 10.1016/j.jmb.2011.06.018
pubmed: 21741390
Abisado, R. G., Benomar, S., Klaus, J. R., Dandekar, A. A. & Chandler, J. R. Bacterial quorum sensing and microbial community interactions. mBio 9, e02331-02317. https://doi.org/10.1128/mBio.02331-17 (2018).
doi: 10.1128/mBio.02331-17
Benito, Y. et al. Probing the structure of RNAIII, the Staphylococcus aureus agr regulatory RNA, and identification of the RNA domain involved in repression of protein A expression. RNA (New York, N.Y.) 6, 668–679. https://doi.org/10.1017/s1355838200992550 (2000).
doi: 10.1017/s1355838200992550
Joo, H. S. et al. Mechanism of gene regulation by a Staphylococcus aureus toxin. mBio https://doi.org/10.1128/mBio.01579-16 (2016).
doi: 10.1128/mBio.01579-16
pubmed: 27795396
pmcid: 5080381
Cheung, G. Y., Wang, R., Khan, B. A., Sturdevant, D. E. & Otto, M. Role of the accessory gene regulator agr in community-associated methicillin-resistant Staphylococcus aureus pathogenesis. Infect. Immun. 79, 1927–1935. https://doi.org/10.1128/iai.00046-11 (2011).
doi: 10.1128/iai.00046-11
pubmed: 21402769
pmcid: 3088142
Fisher, E. L., Otto, M. & Cheung, G. Y. C. Basis of Virulence in enterotoxin-mediated staphylococcal food poisoning. Front. Microbiol. https://doi.org/10.3389/fmicb.2018.00436 (2018).
doi: 10.3389/fmicb.2018.00436
pubmed: 30294314
pmcid: 6158360
Ferreira, F. A. et al. Impact of agr dysfunction on virulence profiles and infections associated with a novel methicillin-resistant Staphylococcus aureus (MRSA) variant of the lineage ST1-SCCmec IV. BMC Microbiol. 13, 93. https://doi.org/10.1186/1471-2180-13-93 (2013).
doi: 10.1186/1471-2180-13-93
pubmed: 23622558
pmcid: 3652751
Tasse, J. et al. Association between biofilm formation phenotype and clonal lineage in Staphylococcus aureus strains from bone and joint infections. PLoS ONE 13, e0200064. https://doi.org/10.1371/journal.pone.0200064 (2018).
doi: 10.1371/journal.pone.0200064
pubmed: 30161132
pmcid: 6116976
Jang, H. C. et al. Difference in agr dysfunction and reduced vancomycin susceptibility between MRSA bacteremia involving SCCmec types IV/IVa and I-III. PLoS ONE 7, e49136. https://doi.org/10.1371/journal.pone.0049136 (2012).
doi: 10.1371/journal.pone.0049136
pubmed: 23152862
pmcid: 3495764
Sheppard, S. K., Guttman, D. S. & Fitzgerald, J. R. Population genomics of bacterial host adaptation. Nat. Rev. Genet. 19, 549–565. https://doi.org/10.1038/s41576-018-0032-z (2018).
doi: 10.1038/s41576-018-0032-z
pubmed: 29973680
Merlino, J. et al. Detection and expression of methicillin/oxacillin resistance in multidrug-resistant and non-multidrug-resistant Staphylococcus aureus in Central Sydney Australia. J. Antimicrob. Chemother. 49, 793–801 (2002).
doi: 10.1093/jac/dkf021
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Twenty-Fourth Informational Supplement M100-S24 (2014).
Clinical and Laboratory Standards Institute (Wayne, PA, 2013).
Bankevich, A. et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J. Comput. Biol. J. Comput. Mol. Cell Biol. 19, 455–477. https://doi.org/10.1089/cmb.2012.0021 (2012).
doi: 10.1089/cmb.2012.0021
Seemann, T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069. https://doi.org/10.1093/bioinformatics/btu153 (2014).
doi: 10.1093/bioinformatics/btu153
pubmed: 24642063
Larsen, M. V. et al. Multilocus sequence typing of total-genome-sequenced bacteria. J. Clin. Microbiol. 50, 1355–1361. https://doi.org/10.1128/jcm.06094-11 (2012).
doi: 10.1128/jcm.06094-11
pubmed: 22238442
pmcid: 3318499
Kearse, M. et al. Geneious basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28, 1647–1649. https://doi.org/10.1093/bioinformatics/bts199 (2012).
doi: 10.1093/bioinformatics/bts199
pubmed: 3371832
pmcid: 3371832
Zankari, E. et al. Identification of acquired antimicrobial resistance genes. J. Antimicrob. Chemother. 67, 2640–2644. https://doi.org/10.1093/jac/dks261 (2012).
doi: 10.1093/jac/dks261
pubmed: 22782487
pmcid: 3468078
Joensen, K. G. et al. Real-time whole-genome sequencing for routine typing, surveillance, and outbreak detection of verotoxigenic Escherichia coli. J. Clin. Microbiol. 52, 1501–1510. https://doi.org/10.1128/jcm.03617-13 (2014).
doi: 10.1128/jcm.03617-13
pubmed: 24574290
pmcid: 3993690
Bartels, M. D. et al. Comparing whole-genome sequencing with Sanger sequencing for spa typing of methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 52, 4305–4308. https://doi.org/10.1128/jcm.01979-14 (2014).
doi: 10.1128/jcm.01979-14
pubmed: 25297335
pmcid: 4313303
von Mentzer, A. et al. Identification of enterotoxigenic Escherichia coli (ETEC) clades with long-term global distribution. Nat. Genet. 46, 1321. https://doi.org/10.1038/ng.3145 (2015).
doi: 10.1038/ng.3145
Stamatakis, A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics (Oxford, England) 30, 1312–1313. https://doi.org/10.1093/bioinformatics/btu033 (2014).
doi: 10.1093/bioinformatics/btu033
Hadfield, J. et al. Phandango: an interactive viewer for bacterial population genomics. Bioinformatics https://doi.org/10.1093/bioinformatics/btx610 (2017).
doi: 10.1093/bioinformatics/btx610
pmcid: 5860215
Cheung, G. Y. C., Duong, A. C. & Otto, M. Direct and synergistic hemolysis caused by Staphylococcus phenol-soluble modulins: implications for diagnosis and pathogenesis. Microbes Infect. 14, 380–386. https://doi.org/10.1016/j.micinf.2011.11.013 (2012).
doi: 10.1016/j.micinf.2011.11.013
pubmed: 22178792
Nair, D. et al. Whole-genome sequencing of Staphylococcus aureus strain RN4220, a key laboratory strain used in virulence research, identifies mutations that affect not only virulence factors but also the fitness of the strain. J. Bacteriol. 193, 2332–2335. https://doi.org/10.1128/jb.00027-11 (2011).
doi: 10.1128/jb.00027-11
pubmed: 21378186
pmcid: 3133102
Montgomery, C. P., Boyle-Vavra, S. & Daum, R. S. Importance of the global regulators Agr and SaeRS in the pathogenesis of CA-MRSA USA300 infection. PLoS ONE 5, e15177. https://doi.org/10.1371/journal.pone.0015177 (2010).
doi: 10.1371/journal.pone.0015177
pubmed: 21151999
pmcid: 2996312
Gase, K., Ferretti, J. J., Primeaux, C. & McShan, W. M. Identification, cloning, and expression of the CAMP factor gene (cfa) of group A streptococci. Infect. Immun. 67, 4725–4731 (1999).
doi: 10.1128/IAI.67.9.4725-4731.1999
Kaito, C. & Sekimizu, K. Colony spreading in Staphylococcus aureus. J. Bacteriol. 189, 2553–2557. https://doi.org/10.1128/JB.01635-06 (2007).
doi: 10.1128/JB.01635-06
pubmed: 17194792
Tsompanidou, E. et al. Requirement of the agr locus for colony spreading of Staphylococcus aureus. J. Bacteriol. 193, 1267–1272. https://doi.org/10.1128/jb.01276-10 (2011).
doi: 10.1128/jb.01276-10
pubmed: 21169484
Lin, M.-H., Ke, W.-J., Liu, C.-C. & Yang, M.-W. Modulation of Staphylococcus aureus spreading by water. Sci. Rep. 6, 25233. https://doi.org/10.1038/srep25233 (2016).
doi: 10.1038/srep25233
pubmed: 27125382
pmcid: 4850448
Tsompanidou, E. et al. The sortase A substrates FnbpA, FnbpB, ClfA and ClfB antagonize colony spreading of Staphylococcus aureus. PLoS ONE 7, e44646. https://doi.org/10.1371/journal.pone.0044646 (2012).
doi: 10.1371/journal.pone.0044646
pubmed: 22970276
pmcid: 3436756
Doellinger, J., Schneider, A., Hoeller, M. & Lasch, P. Sample preparation by easy extraction and digestion (SPEED)—a universal, rapid, and detergent-free protocol for proteomics based on acid extraction. Mol. Cell. Proteom. MCP https://doi.org/10.1074/mcp.TIR119.001616 (2019).
doi: 10.1074/mcp.TIR119.001616
Rappsilber, J., Mann, M. & Ishihama, Y. Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat. Protoc. 2, 1896–1906. https://doi.org/10.1038/nprot.2007.261 (2007).
doi: 10.1038/nprot.2007.261
pubmed: 17703201
Demichev, V., Messner, C. B., Vernardis, S. I., Lilley, K. S. & Ralser, M. DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput. Nat. Methods https://doi.org/10.1038/s41592-019-0638-x (2019).
doi: 10.1038/s41592-019-0638-x
pubmed: 31768060
pmcid: 6949130
Christensen, G. D. et al. Adherence of coagulase-negative staphylococci to plastic tissue culture plates: a quantitative model for the adherence of staphylococci to medical devices. J. Clin. Microbiol. 22, 996–1006 (1985).
doi: 10.1128/JCM.22.6.996-1006.1985
Becker, K., Ballhausen, B., Köck, R. & Kriegeskorte, A. Methicillin resistance in Staphylococcus isolates: the “mec alphabet” with specific consideration of mecC, a mec homolog associated with zoonotic S. aureus lineages. Int. J. Med. Microbiol. 304, 794–804. https://doi.org/10.1016/j.ijmm.2014.06.007 (2014).
doi: 10.1016/j.ijmm.2014.06.007
pubmed: 25034857
Fitzgerald, J. R. et al. Characterization of a putative pathogenicity island from bovine Staphylococcus aureus encoding multiple superantigens. J. Bacteriol. 183, 63–70. https://doi.org/10.1128/jb.183.1.63-70.2001 (2001).
doi: 10.1128/jb.183.1.63-70.2001
pubmed: 11114901
pmcid: 94850
Bosi, E. et al. Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity. Proc. Natl. Acad. Sci. USA 113, E3801-3809. https://doi.org/10.1073/pnas.1523199113 (2016).
doi: 10.1073/pnas.1523199113
pubmed: 27286824
Monecke, S. et al. Detection of mecC-positive Staphylococcus aureus (CC130-MRSA-XI) in diseased European hedgehogs (Erinaceus europaeus) in Sweden. PLoS ONE 8, e66166. https://doi.org/10.1371/journal.pone.0066166 (2013).
doi: 10.1371/journal.pone.0066166
pubmed: 23776626
pmcid: 3680430
Shopsin, B. et al. Prevalence of agr specificity groups among Staphylococcus aureus strains colonizing children and their guardians. J. Clin. Microbiol. 41, 456–459. https://doi.org/10.1128/jcm.41.1.456-459.2003 (2003).
doi: 10.1128/jcm.41.1.456-459.2003
pubmed: 12517893
pmcid: 149583
Queck, S. Y. et al. RNAIII-independent target gene control by the agr quorum-sensing system: insight into the evolution of virulence regulation in Staphylococcus aureus. Mol. Cell 32, 150–158. https://doi.org/10.1016/j.molcel.2008.08.005 (2008).
doi: 10.1016/j.molcel.2008.08.005
pubmed: 18851841
pmcid: 2575650
Morrison, J. M., Anderson, K. L., Beenken, K. E., Smeltzer, M. S. & Dunman, P. M. The staphylococcal accessory regulator, SarA, is an RNA-binding protein that modulates the mRNA turnover properties of late-exponential and stationary phase Staphylococcus aureus cells. Front. Cell. Infect. Microbiol. 2, 26. https://doi.org/10.3389/fcimb.2012.00026 (2012).
doi: 10.3389/fcimb.2012.00026
pubmed: 22919618
pmcid: 3417590
Traber, K. & Novick, R. A slipped-mispairing mutation in AgrA of laboratory strains and clinical isolates results in delayed activation of agr and failure to translate δ- and α-haemolysins. Mol. Microbiol. 59, 1519–1530. https://doi.org/10.1111/j.1365-2958.2006.04986.x (2006).
doi: 10.1111/j.1365-2958.2006.04986.x
pubmed: 16468992
Vincze, S. et al. Alarming proportions of methicillin-resistant Staphylococcus aureus (MRSA) in wound samples from companion animals, Germany 2010–2012. PLoS ONE 9, e85656. https://doi.org/10.1371/journal.pone.0085656 (2014).
doi: 10.1371/journal.pone.0085656
pubmed: 24465637
pmcid: 3896405
Kaspar, U. et al. Zoonotic multidrug-resistant microorganisms among small companion animals in Germany. PLoS ONE 13, e0208364. https://doi.org/10.1371/journal.pone.0208364 (2018).
doi: 10.1371/journal.pone.0208364
pubmed: 30532196
pmcid: 6285998
Sidote, D. J., Barbieri, C. M., Wu, T. & Stock, A. M. Structure of the Staphylococcus aureus AgrA LytTR domain bound to DNA reveals a beta fold with an unusual mode of binding. Structure 16, 727–735. https://doi.org/10.1016/j.str.2008.02.011 (2008).
doi: 10.1016/j.str.2008.02.011
pubmed: 18462677
pmcid: 2430735
George Cisar, E. A., Geisinger, E., Muir, T. W. & Novick, R. P. Symmetric signalling within asymmetric dimers of the Staphylococcus aureus receptor histidine kinase AgrC. Mol. Microbiol. 74, 44–57. https://doi.org/10.1111/j.1365-2958.2009.06849.x (2009).
doi: 10.1111/j.1365-2958.2009.06849.x
pubmed: 19708918
pmcid: 3913215
Recsei, P. et al. Regulation of exoprotein gene expression in Staphylococcus aureus by agar. Mol. Gen. Genet. MGG 202, 58–61. https://doi.org/10.1007/bf00330517 (1986).
doi: 10.1007/bf00330517
pubmed: 3007938
Morfeldt, E., Taylor, D., von Gabain, A. & Arvidson, S. Activation of alpha-toxin translation in Staphylococcus aureus by the trans-encoded antisense RNA RNAIII. EMBO J. 14, 4569–4577 (1995).
doi: 10.1002/j.1460-2075.1995.tb00136.x
Wang, X., Thompson, C. D., Weidenmaier, C. & Lee, J. C. Release of Staphylococcus aureus extracellular vesicles and their application as a vaccine platform. Nat. Commun. 9, 1379. https://doi.org/10.1038/s41467-018-03847-z (2018).
doi: 10.1038/s41467-018-03847-z
pubmed: 29643357
pmcid: 5895597
Dastgheyb, S. S. & Otto, M. Staphylococcal adaptation to diverse physiologic niches: an overview of transcriptomic and phenotypic changes in different biological environments. Future Microbiol. 10, 1981–1995. https://doi.org/10.2217/fmb.15.116 (2015).
doi: 10.2217/fmb.15.116
pubmed: 26584249
pmcid: 4946774
Dai, L. et al. Staphylococcus epidermidis recovered from indwelling catheters exhibit enhanced biofilm dispersal and “self-renewal” through downregulation of agr. BMC Microbiol. 12, 102. https://doi.org/10.1186/1471-2180-12-102 (2012).
doi: 10.1186/1471-2180-12-102
pubmed: 22682058
pmcid: 3458918
Cafiso, V. et al. agr-Genotyping and transcriptional analysis of biofilm-producing Staphylococcus aureus. FEMS Immunol. Med. Microbiol. 51, 220–227. https://doi.org/10.1111/j.1574-695X.2007.00298.x (2007).
doi: 10.1111/j.1574-695X.2007.00298.x
pubmed: 17854479
Kong, K. F., Vuong, C. & Otto, M. Staphylococcus quorum sensing in biofilm formation and infection. Int. J. Med. Microbiol. IJMM 296, 133–139. https://doi.org/10.1016/j.ijmm.2006.01.042 (2006).
doi: 10.1016/j.ijmm.2006.01.042
pubmed: 16487744
Beenken, K. E. et al. Epistatic relationships between sarA and agr in Staphylococcus aureus biofilm formation. PLoS ONE 5, e10790. https://doi.org/10.1371/journal.pone.0010790 (2010).
doi: 10.1371/journal.pone.0010790
pubmed: 20520723
pmcid: 2875390
Wang, R. et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat. Med. 13, 1510–1514. https://doi.org/10.1038/nm1656 (2007).
doi: 10.1038/nm1656
pubmed: 17994102
Periasamy, S. et al. How Staphylococcus aureus biofilms develop their characteristic structure. Proc. Natl. Acad. Sci. USA 109, 1281–1286. https://doi.org/10.1073/pnas.1115006109 (2012).
doi: 10.1073/pnas.1115006109
pubmed: 22232686
Moormeier, D. E. & Bayles, K. W. Staphylococcus aureus biofilm: a complex developmental organism. Mol. Microbiol. 104, 365–376. https://doi.org/10.1111/mmi.13634 (2017).
doi: 10.1111/mmi.13634
pubmed: 28142193
pmcid: 5397344
Foster, T. J., Geoghegan, J. A., Ganesh, V. K. & Hook, M. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat. Rev. Microbiol. 12, 49–62. https://doi.org/10.1038/nrmicro3161 (2014).
doi: 10.1038/nrmicro3161
pubmed: 24336184
pmcid: 5708296
Sadykov, M. R. & Bayles, K. W. The control of death and lysis in staphylococcal biofilms: a coordination of physiological signals. Curr. Opin. Microbiol. 15, 211–215. https://doi.org/10.1016/j.mib.2011.12.010 (2012).
doi: 10.1016/j.mib.2011.12.010
pubmed: 22221897
pmcid: 3320683
Diard, M. & Hardt, W. D. Evolution of bacterial virulence. FEMS Microbiol. Rev. 41, 679–697. https://doi.org/10.1093/femsre/fux023 (2017).
doi: 10.1093/femsre/fux023
pubmed: 28531298
Priest, N. K. et al. From genotype to phenotype: can systems biology be used to predict Staphylococcus aureus virulence?. Nat. Rev. Microbiol. 10, 791–797. https://doi.org/10.1038/nrmicro2880 (2012).
doi: 10.1038/nrmicro2880
pubmed: 23070558
pmcid: 7097209
Kahl, B. C., Becker, K. & Loffler, B. Clinical significance and pathogenesis of staphylococcal small colony variants in persistent infections. Clin. Microbiol. Rev. 29, 401–427. https://doi.org/10.1128/cmr.00069-15 (2016).
doi: 10.1128/cmr.00069-15
pubmed: 26960941
pmcid: 4786882
Tuchscherr, L. et al. Clinical S. aureus isolates vary in their virulence to promote adaptation to the host. Toxins (Basel) https://doi.org/10.3390/toxins11030135 (2019).
doi: 10.3390/toxins11030135
Fraunholz, M. & Sinha, B. Intracellular Staphylococcus aureus: live-in and let die. Front. Cell. Infect. Microbiol. 2, 43. https://doi.org/10.3389/fcimb.2012.00043 (2012).
doi: 10.3389/fcimb.2012.00043
pubmed: 22919634
pmcid: 3417557
Cuny, C. et al. Methicillin-resistant Staphylococcus aureus from infections in horses in Germany are frequent colonizers of veterinarians but rare among MRSA from infections in humans. One Health (Amsterdam, Netherlands) 2, 11–17. https://doi.org/10.1016/j.onehlt.2015.11.004 (2016).
doi: 10.1016/j.onehlt.2015.11.004
Golubchik, T. et al. Within-host evolution of Staphylococcus aureus during asymptomatic carriage. PLoS ONE 8, e61319. https://doi.org/10.1371/journal.pone.0061319 (2013).
doi: 10.1371/journal.pone.0061319
pubmed: 23658690
pmcid: 3641031
Skallerup, P., Espinosa-Gongora, C., Jorgensen, C. B., Guardabassi, L. & Fredholm, M. Genome-wide association study reveals a locus for nasal carriage of Staphylococcus aureus in Danish crossbred pigs. BMC Vet. Res. 11, 290. https://doi.org/10.1186/s12917-015-0599-y (2015).
doi: 10.1186/s12917-015-0599-y
pubmed: 26612358
pmcid: 4662016
Holtfreter, S. et al. Molecular epidemiology of Staphylococcus aureus in the general population in Northeast Germany: results of the study of health in Pomerania (SHIP-TREND-0). J. Clin. Microbiol. 54, 2774–2785. https://doi.org/10.1128/jcm.00312-16 (2016).
doi: 10.1128/jcm.00312-16
pubmed: 27605711
pmcid: 5078557
Pollitt, E. J., West, S. A., Crusz, S. A., Burton-Chellew, M. N. & Diggle, S. P. Cooperation, quorum sensing, and evolution of virulence in Staphylococcus aureus. Infect. Immun. 82, 1045–1051. https://doi.org/10.1128/iai.01216-13 (2014).
doi: 10.1128/iai.01216-13
pubmed: 24343650
pmcid: 3957977
Paulander, W. et al. Antibiotic-mediated selection of quorum-sensing-negative Staphylococcus aureus. mBio 3, e00459-00412. https://doi.org/10.1128/mBio.00459-12 (2013).
doi: 10.1128/mBio.00459-12
George, S. E. et al. Oxidative stress drives the selection of quorum sensing mutants in the Staphylococcus aureus population. Proc. Natl. Acad. Sci. USA 116, 19145–19154. https://doi.org/10.1073/pnas.1902752116 (2019).
doi: 10.1073/pnas.1902752116
pubmed: 31488708
Schlievert, P. M. et al. Pyrogenic toxin superantigen site specificity in toxic shock syndrome and food poisoning in animals. Infect. Immun. 68, 3630–3634. https://doi.org/10.1128/iai.68.6.3630-3634.2000 (2000).
doi: 10.1128/iai.68.6.3630-3634.2000
pubmed: 10816521
pmcid: 97652
Regassa, L. B. & Betley, M. J. High sodium chloride concentrations inhibit staphylococcal enterotoxin C gene (sec) expression at the level of sec mRNA. Infect. Immun. 61, 1581–1585 (1993).
doi: 10.1128/IAI.61.4.1581-1585.1993
Amissah, N. A. et al. Virulence potential of Staphylococcus aureus isolates from Buruli ulcer patients. Int. J. Med. Microbiol. 307, 223–232. https://doi.org/10.1016/j.ijmm.2017.04.002 (2017).
doi: 10.1016/j.ijmm.2017.04.002
pubmed: 28442219