The Genome of a Pathogenic : Cooptive Virulence Underpinned by Key Gene Acquisitions

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We report the genome of the facultative intracellular parasite Rhodococcus equi, the only animal pathogen within the biotechnologically important actinobacterial genus Rhodococcus. The 5.0-Mb R. equi 103S genome is significantly smaller than those of environmental rhodococci. This is due to genome expansion in nonpathogenic species, via a linear gain of paralogous genes and an accelerated genetic flux, rather than reductive evolution in R. equi. The 103S genome lacks the extensive catabolic and secondary metabolic complement of environmental rhodococci, and it displays unique adaptations for host colonization and competition in the short-chain fatty acid–rich intestine and manure of herbivores—two main R. equi reservoirs. Except for a few horizontally acquired (HGT) pathogenicity loci, including a cytoadhesive pilus determinant (rpl) and the virulence plasmid vap pathogenicity island (PAI) required for intramacrophage survival, most of the potential virulence-associated genes identified in R. equi are conserved in environmental rhodococci or have homologs in nonpathogenic Actinobacteria. This suggests a mechanism of virulence evolution based on the cooption of existing core actinobacterial traits, triggered by key host niche–adaptive HGT events. We tested this hypothesis by investigating R. equi virulence plasmid-chromosome crosstalk, by global transcription profiling and expression network analysis. Two chromosomal genes conserved in environmental rhodococci, encoding putative chorismate mutase and anthranilate synthase enzymes involved in aromatic amino acid biosynthesis, were strongly coregulated with vap PAI virulence genes and required for optimal proliferation in macrophages. The regulatory integration of chromosomal metabolic genes under the control of the HGT–acquired plasmid PAI is thus an important element in the cooptive virulence of R. equi.

Vyšlo v časopise: The Genome of a Pathogenic : Cooptive Virulence Underpinned by Key Gene Acquisitions. PLoS Genet 6(9): e32767. doi:10.1371/journal.pgen.1001145
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001145

Souhrn

Zdroje

1. GurtlerV

MayallBC

SeviourR

2004 Can whole genome analysis refine the taxonomy of the genus Rhodococcus? FEMS Microbiol Rev 28 377 403

2. LarkinMJ

KulakovLA

AllenCC

2005 Biodegradation and Rhodococcus–masters of catabolic versatility. Curr Opin Biotechnol 16 282 290

3. MuscatelloG

LeadonDP

KlaytM

Ocampo-SosaA

LewisDA

2007 Rhodococcus equi infection in foals: the science of ‘rattles’. Equine Vet J 39 470 478

4. Vazquez-BolandJA

LetekM

ValeroA

GonzalezP

ScorttiM

FogartyU

2010 Rhodococcus equi and its pathogenic mechanisms

AlvarezHM

Biology of Rhodococcus, Microbiology Mongraphs 16 Berlin Heidelberg Spinger-Verlag(in press)

5. HondalusMK

MosserDM

1994 Survival and replication of Rhodococcus equi in macrophages. Infect Immun 62 4167 4175

6. WadaR

KamadaM

AnzaiT

NakanishiA

KanemaruT

1997 Pathogenicity and virulence of Rhodococcus equi in foals following intratracheal challenge. Vet Microbiol 56 301 312

7. von BargenK

HaasA

2009 Molecular and infection biology of the horse pathogen Rhodococcus equi. FEMS Microbiol Rev 33 870 891

8. LetekM

Ocampo-SosaAA

SandersM

FogartyU

BuckleyT

2008 Evolution of the Rhodococcus equi vap pathogenicity island seen through comparison of host-associated vapA and vapB virulence plasmids. J Bacteriol 190 5797 5805

9. Ocampo-SosaAA

LewisDA

NavasJ

QuigleyF

CallejoR

2007 Molecular epidemiology of Rhodococcus equi based on traA, vapA, and vapB virulence plasmid markers. J Infect Dis 196 763 769

10. McLeodMP

WarrenRL

HsiaoWW

ArakiN

MyhreM

2006 The complete genome of Rhodococcus sp. RHA1 provides insights into a catabolic powerhouse. Proc Natl Acad Sci U S A 103 15582 15587

11. GoodfellowM

AldersonG

ChunJ

1998 Rhodococcal systematics: problems and developments. Antonie Van Leeuwenhoek 74 3 20

12. BentleySD

ChaterKF

Cerdeno-TarragaAM

ChallisGL

ThomsonNR

2002 Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417 141 147

13. ColeST

BroschR

ParkhillJ

GarnierT

ChurcherC

1998 Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393 537 544

14. QuinnPJ

CarterME

MarkeyB

CarterGR

1994 Corynebacterium species and Rhodococcus equi. Clinical Veterinary Microbiology London Mosby International 137 143

15. BochnerBR

2009 Global phenotypic characterization of bacteria. FEMS Microbiol Rev 33 191 205

16. ZaitsevGM

UotilaJS

TsitkoIV

LobanokAG

Salkinoja-SalonenMS

1995 Utilization of halogenated benzenes, phenols, and benzoates by Rhodococcus opacus GM-14. Appl Environ Microbiol 61 4191 4201

17. SetoM

KimbaraK

ShimuraM

HattaT

FukudaM

1995 A novel transformation of polychlorinated biphenyls by Rhodococcus sp. strain RHA1. Appl Environ Microbiol 61 3353 3358

18. van der GeizeR

HesselsGI

DijkhuizenL

2002 Molecular and functional characterization of the kstD2 gene of Rhodococcus erythropolis SQ1 encoding a second 3-ketosteroid Delta(1)-dehydrogenase isoenzyme. Microbiology 148 3285 3292

19. KellyBG

WallDM

BolandCA

MeijerWG

2002 Isocitrate lyase of the facultative intracellular pathogen Rhodococcus equi. Microbiology 148 793 798

20. Muñoz-EliasEJ

McKinneyJD

2006 Carbon metabolism of intracellular bacteria. Cell Microbiol 8 10 22

21. WallDM

DuffyPS

DupontC

PrescottJF

MeijerWG

2005 Isocitrate lyase activity is required for virulence of the intracellular pathogen Rhodococcus equi. Infect Immun 73 6736 6741

22. McKinneyJD

Honer zu BentrupK

Munoz-EliasEJ

MiczakA

ChenB

2000 Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406 735 738

23. Hingley-WilsonSM

SambandamurthyVK

JacobsWRJr

2003 Survival perspectives from the world's most successful pathogen, Mycobacterium tuberculosis. Nat Immunol 4 949 955

24. WayneLG

SohaskeyCD

2001 Nonreplicating persistence of Mycobacterium tuberculosis. Annu Rev Microbiol 55 139 163

25. PeiY

ParreiraV

NicholsonVM

PrescottJF

2007 Mutation and virulence assessment of chromosomal genes of Rhodococcus equi 103. Can J Vet Res 71 1 7

26. MalmS

TiffertY

MicklinghoffJ

SchultzeS

JoostI

2009 The roles of the nitrate reductase NarGHJI, the nitrite reductase NirBD and the response regulator GlnR in nitrate assimilation of Mycobacterium tuberculosis. Microbiology 155 1332 1339

27. SchellMA

KarmirantzouM

SnelB

VilanovaD

BergerB

2002 The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract. Proc Natl Acad Sci U S A 99 14422 14427

28. EschbachM

SchreiberK

TrunkK

BuerJ

JahnD

2004 Long-term anaerobic survival of the opportunistic pathogen Pseudomonas aeruginosa via pyruvate fermentation. J Bacteriol 186 4596 4604

29. ChaiY

KolterR

LosickR

2009 A widely conserved gene cluster required for lactate utilization in Bacillus subtilis and its involvement in biofilm formation. J Bacteriol 191 2423 2430

30. van VlietAH

StoofJ

PoppelaarsSW

BereswillS

HomuthG

2003 Differential regulation of amidase- and formamidase-mediated ammonia production by the Helicobacter pylori fur repressor. J Biol Chem 278 9052 9057

31. DuzM

WhittakerAG

LoveS

ParkinTD

HughesKJ

2009 Exhaled breath condensate hydrogen peroxide and pH for the assessment of lower airway inflammation in the horse. Res Vet Sci 87 307 312

32. MiyahiM

UedaK

KobayashiY

HataH

KondoS

2008 Fiber digestion in various segments of the hindgut of horses fed grass hay or silage. Anim Sci J 79 339 346

33. MongodinEF

ShapirN

DaughertySC

DeBoyRT

EmersonJB

2006 Secrets of soil survival revealed by the genome sequence of Arthrobacter aurescens TC1. PLoS Genet 2 e214 doi:10.1371/journal.pgen.0020214

34. PotrykusK

CashelM

2008 (p)ppGpp: still magical? Annu Rev Microbiol 62 35 51

35. NewtonGL

BuchmeierN

FaheyRC

2008 Biosynthesis and functions of mycothiol, the unique protective thiol of Actinobacteria. Microbiol Mol Biol Rev 72 471 494

36. SasindranSJ

SaikolappanS

DhandayuthapaniS

2007 Methionine sulfoxide reductases and virulence of bacterial pathogens. Future Microbiol 2 619 630

37. ColangeliR

HaqA

ArcusVL

SummersE

MagliozzoRS

2009 The multifunctional histone-like protein Lsr2 protects mycobacteria against reactive oxygen intermediates. Proc Natl Acad Sci U S A 106 4414 4418

38. HaikarainenT

PapageorgiouAC

2009 Dps-like proteins: structural and functional insights into a versatile protein family. Cell Mol Life Sci

39. PragaiZ

HarwoodCR

2002 Regulatory interactions between the Pho and sigma(B)-dependent general stress regulons of Bacillus subtilis. Microbiology 148 1593 1602

40. MartinezJL

2009 The role of natural environments in the evolution of resistance traits in pathogenic bacteria. Proc Biol Sci 276 2521 2530

41. UnderwoodAP

MulderA

GharbiaS

GreenJ

2005 Virulence Searcher: a tool for searching raw genome sequences from bacterial genomes for putative virulence factors. Clin Microbiol Infect 11 770 772

42. CasaliN

RileyLW

2007 A phylogenomic analysis of the Actinomycetales mce operons. BMC Genomics 8 60

43. van der GeizeR

de JongW

HesselsGI

GrommenAW

JacobsAA

2008 A novel method to generate unmarked gene deletions in the intracellular pathogen Rhodococcus equi using 5-fluorocytosine conditional lethality. Nucleic Acids Res 36 e151

44. MohnWW

van der GeizeR

StewartGR

OkamotoS

LiuJ

2008 The actinobacterial mce4 locus encodes a steroid transporter. J Biol Chem 283 35368 35374

45. JoshiSM

PandeyAK

CapiteN

FortuneSM

RubinEJ

2006 Characterization of mycobacterial virulence genes through genetic interaction mapping. Proc Natl Acad Sci U S A 103 11760 11765

46. Gey van PittiusNC

SampsonSL

LeeH

KimY

van HeldenPD

2006 Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions. BMC Evol Biol 6 95

47. StrongM

SawayaMR

WangS

PhillipsM

CascioD

2006 Toward the structural genomics of complexes: crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 103 8060 8065

48. SimeoneR

BottaiD

BroschR

2009 ESX/type VII secretion systems and their role in host-pathogen interaction. Curr Opin Microbiol 12 4 10

49. JainM

CoxJS

2005 Interaction between polyketide synthase and transporter suggests coupled synthesis and export of virulence lipid in M. tuberculosis. PLoS Pathog 1 e2 doi:10.1371/journal.ppat.0010002

50. PuechV

GuilhotC

PerezE

TropisM

ArmitigeLY

2002 Evidence for a partial redundancy of the fibronectin-binding proteins for the transfer of mycoloyl residues onto the cell wall arabinogalactan termini of Mycobacterium tuberculosis. Mol Microbiol 44 1109 1122

51. TomichM

PlanetPJ

FigurskiDH

2007 The tad locus: postcards from the widespread colonization island. Nat Rev Microbiol 5 363 375

52. MandlikA

SwierczynskiA

DasA

Ton-ThatH

2008 Pili in Gram-positive bacteria: assembly, involvement in colonization and biofilm development. Trends Microbiol 16 33 40

53. AlteriCJ

Xicohtencatl-CortesJ

HessS

Caballero-OlinG

GironJA

2007 Mycobacterium tuberculosis produces pili during human infection. Proc Natl Acad Sci U S A 104 5145 5150

54. PrescottJF

1991 Rhodococcus equi: an animal and human pathogen. Clin Microbiol Rev 4 20 34

55. MarraffiniLA

DedentAC

SchneewindO

2006 Sortases and the art of anchoring proteins to the envelopes of gram-positive bacteria. Microbiol Mol Biol Rev 70 192 221

56. NavasJ

Gonzalez-ZornB

LadronN

GarridoP

Vazquez-BolandJA

2001 Identification and mutagenesis by allelic exchange of choE, encoding a cholesterol oxidase from the intracellular pathogen Rhodococcus equi. J Bacteriol 183 4796 4805

57. ParkerSK

CurtinKM

VasilML

2007 Purification and characterization of mycobacterial phospholipase A: an activity associated with mycobacterial cutinase. J Bacteriol 189 4153 4160

58. Said-SalimB

MostowyS

KristofAS

BehrMA

2006 Mutations in Mycobacterium tuberculosis Rv0444c, the gene encoding anti-SigK, explain high level expression of MPB70 and MPB83 in Mycobacterium bovis. Mol Microbiol 62 1251 1263

59. ParkSY

JungMY

KimIS

2009 Stabilin-2 mediates homophilic cell-cell interactions via its FAS1 domains. FEBS Lett 583 1375 1380

60. PetheK

BifaniP

DrobecqH

SergheraertC

DebrieAS

2002 Mycobacterial heparin-binding hemagglutinin and laminin-binding protein share antigenic methyllysines that confer resistance to proteolysis. Proc Natl Acad Sci U S A 99 10759 10764

61. Miranda-CasoLuengoR

PrescottJF

Vazquez-BolandJA

MeijerWG

2008 The intracellular pathogen Rhodococcus equi produces a catecholate siderophore required for saprophytic growth. J Bacteriol 190 1631 1637

62. RatledgeC

2004 Iron, mycobacteria and tuberculosis. Tuberculosis (Edinb) 84 110 130

63. Gey Van PittiusNC

GamieldienJ

HideW

BrownGD

SiezenRJ

2001 The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G+C Gram-positive bacteria. Genome Biol 2 RESEARCH0044

64. IshikawaJ

YamashitaA

MikamiY

HoshinoY

KuritaH

2004 The complete genomic sequence of Nocardia farcinica IFM 10152. Proc Natl Acad Sci U S A 101 14925 14930

65. TrueJR

CarrollSB

2002 Gene co-option in physiological and morphological evolution. Annu Rev Cell Dev Biol 18 53 80

66. McLennanDA

2008 The concept of co-option: why evolution often looks miraculous. Evo Devo Outreach 1 247 258

67. GanforninaMD

SanchezD

1999 Generation of evolutionary novelty by functional shift. Bioessays 21 432 439

68. KonstantinidisKT

TiedjeJM

2004 Trends between gene content and genome size in prokaryotic species with larger genomes. Proc Natl Acad Sci U S A 101 3160 3165

69. LynchM

KatjuV

2004 The altered evolutionary trajectories of gene duplicates. Trends Genet 20 544 549

70. ParkHD

GuinnKM

HarrellMI

LiaoR

VoskuilMI

2003 Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis. Mol Microbiol 48 833 843

71. Chico-CaleroI

SuarezM

Gonzalez-ZornB

ScorttiM

SlaghuisJ

2002 Hpt, a bacterial homolog of the microsomal glucose- 6-phosphate translocase, mediates rapid intracellular proliferation in Listeria. Proc Natl Acad Sci U S A 99 431 436

72. ByrneGA

RussellDA

ChenX

MeijerWG

2007 Transcriptional regulation of the virR operon of the intracellular pathogen Rhodococcus equi. J Bacteriol 189 5082 5089

73. ByrneBA

PrescottJF

PalmerGH

TakaiS

NicholsonVM

2001 Virulence plasmid of Rhodococcus equi contains inducible gene family encoding secreted proteins. Infect Immun 69 650 656

74. FreemanTC

GoldovskyL

BroschM

van DongenS

MaziereP

2007 Construction, visualisation, and clustering of transcription networks from microarray expression data. PLoS Comput Biol 3 e206 doi:10.1371/journal.pcbi.0030206

75. TheocharidisA

van DongenS

EnrightAJ

FreemanTC

2009 Network visualization and analysis of gene expression data using BioLayout Express3D. Nat Protoc 4 1535 1550

76. BarabasiAL

OltvaiZN

2004 Network biology: understanding the cell's functional organization. Nat Rev Genet 5 101 113

77. RenJ

PrescottJF

2004 The effect of mutation on Rhodococcus equi virulence plasmid gene expression and mouse virulence. Vet Microbiol 103 219 230

78. RussellDA

ByrneGA

O'ConnellEP

BolandCA

MeijerWG

2004 The LysR-type transcriptional regulator VirR is required for expression of the virulence gene vapA of Rhodococcus equi ATCC 33701. J Bacteriol 186 5576 5584

79. DosselaereF

VanderleydenJ

2001 A metabolic node in action: chorismate-utilizing enzymes in microorganisms. Crit Rev Microbiol 27 75 131

80. FieldsPI

SwansonRV

HaidarisCG

HeffronF

1986 Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A 83 5189 5193

81. FoulongneV

WalravensK

BourgG

BoschiroliML

GodfroidJ

2001 Aromatic compound-dependent Brucella suis is attenuated in both cultured cells and mouse models. Infect Immun 69 547 550

82. BentleySD

CortonC

BrownSE

BarronA

ClarkL

2008 Genome of the actinomycete plant pathogen Clavibacter michiganensis subsp. sepedonicus suggests recent niche adaptation. J Bacteriol 190 2150 2160

83. SohaskeyCD

2008 Nitrate enhances the survival of Mycobacterium tuberculosis during inhibition of respiration. J Bacteriol 190 2981 2986

84. VoskuilMI

SchnappingerD

ViscontiKC

HarrellMI

DolganovGM

2003 Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J Exp Med 198 705 713

85. WassenaarTM

GaastraW

2001 Bacterial virulence: can we draw the line? FEMS Microbiol Lett 201 1 7

86. BabaH

NadaT

OhkusuK

EzakiT

HasegawaY

2009 First case of bloodstream infection caused by Rhodococcus erythropolis. J Clin Microbiol 47 2667 2669

87. FelsensteinJ

1989 PHYLIP - Phylogeny Inference Package (Version 3.2). Cladistics 5 164 166

88. HongY

HondalusMK

2008 Site-specific integration of Streptomyces PhiC31 integrase-based vectors in the chromosome of Rhodococcus equi. FEMS Microbiol Lett 287 63 68

89. Gonzalez-ZornB

Dominguez-BernalG

SuarezM

RipioMT

VegaY

1999 The smcL gene of Listeria ivanovii encodes a sphingomyelinase C that mediates bacterial escape from the phagocytic vacuole. Mol Microbiol 33 510 523

90. MayJJ

WendrichTM

MarahielMA

2001 The dhb operon of Bacillus subtilis encodes the biosynthetic template for the catecholic siderophore 2,3-dihydroxybenzoate-glycine-threonine trimeric ester bacillibactin. J Biol Chem 276 7209 7217

91. MiethkeM

MarahielMA

2007 Siderophore-based iron acquisition and pathogen control. Microbiol Mol Biol Rev 71 413 451

92. VernikosGS

ParkhillJ

2006 Interpolated variable order motifs for identification of horizontally acquired DNA: revisiting the Salmonella pathogenicity islands. Bioinformatics 22 2196 2203

93. KeselerIM

Bonavides-MartinezC

Collado-VidesJ

Gama-CastroS

GunsalusRP

2009 EcoCyc: a comprehensive view of Escherichia coli biology. Nucleic Acids Res 37 D464 470

94. Martinez-GomezNC

DownsDM

2008 ThiC is an [Fe-S] cluster protein that requires AdoMet to generate the 4-amino-5-hydroxymethyl-2-methylpyrimidine moiety in thiamin synthesis. Biochemistry 47 9054 9056

95. GhoshA

PaulD

PrakashD

MayilrajS

JainRK

2006 Rhodococcus imtechensis sp. nov., a nitrophenol-degrading actinomycete. Int J Syst Evol Microbiol 56 1965 1969

96. YoonJH

ChoYG

KangSS

KimSB

LeeST

2000 Rhodococcus koreensis sp. nov., a 2,4-dinitrophenol-degrading bacterium. Int J Syst Evol Microbiol 50 Pt 3 1193 1201

97. MayilrajS

KrishnamurthiS

SahaP

SainiHS

2006 Rhodococcus kroppenstedtii sp. nov., a novel actinobacterium isolated from a cold desert of the Himalayas, India. Int J Syst Evol Microbiol 56 979 982

98. WangYX

WangHB

ZhangYQ

XuLH

JiangCL

2008 Rhodococcus kunmingensis sp. nov., an actinobacterium isolated from a rhizosphere soil. Int J Syst Evol Microbiol 58 1467 1471

99. LiB

FurihataK

DingLX

YokotaA

2007 Rhodococcus kyotonensis sp. nov., a novel actinomycete isolated from soil. Int J Syst Evol Microbiol 57 1956 1959

100. BrigliaM

RaineyFA

StackebrandtE

SchraaG

Salkinoja-SalonenMS

1996 Rhodococcus percolatus sp. nov., a bacterium degrading 2,4,6-trichlorophenol. Int J Syst Bacteriol 46 23 30

101. YoonJH

KangSS

ChoYG

LeeST

KhoYH

2000 Rhodococcus pyridinivorans sp. nov., a pyridine-degrading bacterium. Int J Syst Evol Microbiol 50 Pt 6 2173 2180

102. MatsuyamaH

YumotoI

KudoT

ShidaO

2003 Rhodococcus tukisamuensis sp. nov., isolated from soil. Int J Syst Evol Microbiol 53 1333 1337

103. ZhangYQ

LiWJ

KroppenstedtRM

KimCJ

ChenGZ

2005 Rhodococcus yunnanensis sp. nov., a mesophilic actinobacterium isolated from forest soil. Int J Syst Evol Microbiol 55 1133 1137

104. BottaiD

BroschR

2009 Mycobacterial PE, PPE and ESX clusters: novel insights into the secretion of these most unusual protein families. Mol Microbiol 73 325 328

105. MaressoAW

SchneewindO

2008 Sortase as a target of anti-infective therapy. Pharmacol Rev 60 128 141

106. SekineM

TanikawaS

OmataS

SaitoM

FujisawaT

2006 Sequence analysis of three plasmids harboured in Rhodococcus erythropolis strain PR4. Environ Microbiol 8 334 346

107. FlorczykMA

McCueLA

PurkayasthaA

CurrentiE

WolinMJ

2003 A family of acr-coregulated Mycobacterium tuberculosis genes shares a common DNA motif and requires Rv3133c (dosR or devR) for expression. Infect Immun 71 5332 5343

108. ChauhanS

TyagiJS

2008 Interaction of DevR with multiple binding sites synergistically activates divergent transcription of narK2-Rv1738 genes in Mycobacterium tuberculosis. J Bacteriol 190 5394 5403

109. PriceMN

DehalPS

ArkinAP

2007 Orthologous transcription factors in bacteria have different functions and regulate different genes. PLoS Comput Biol 3 e175 doi:10.1371/journal.pcbi.0030175

110. DrummJE

MiK

BilderP

SunM

LimJ

2009 Mycobacterium tuberculosis universal stress protein Rv2623 regulates bacillary growth by ATP-Binding: requirement for establishing chronic persistent infection. PLoS Pathog 5 e1000460 doi:10.1371/journal.ppat.1000460

111. NordmannP

RoncoE

1992 In-vitro antimicrobial susceptibility of Rhodococcus equi. J Antimicrob Chemother 29 383 393

112. McNeilMM

BrownJM

1992 Distribution and antimicrobial susceptibility of Rhodococcus equi from clinical specimens. Eur J Epidemiol 8 437 443

113. MascellinoMT

IonaE

PonzoR

MastroianniCM

DeliaS

1994 Infections due to Rhodococcus equi in three HIV-infected patients: microbiological findings and antibiotic susceptibility. Int J Clin Pharmacol Res 14 157 163

114. SorianoF

ZapardielJ

NietoE

1995 Antimicrobial susceptibilities of Corynebacterium species and other non-spore-forming gram-positive bacilli to 18 antimicrobial agents. Antimicrob Agents Chemother 39 208 214

115. MakraiL

FodorL

CsivincsikA

VargaJ

SenonerZ

2000 Characterisation of Rhodococcus equi strains isolated from foals and from immunocompromised human patients. Acta Vet Hung 48 253 259

116. JacksSS

GiguereS

NguyenA

2003 In vitro susceptibilities of Rhodococcus equi and other common equine pathogens to azithromycin, clarithromycin, and 20 other antimicrobials. Antimicrob Agents Chemother 47 1742 1745

117. RutherfordK

ParkhillJ

CrookJ

HorsnellT

RiceP

2000 Artemis: sequence visualization and annotation. Bioinformatics 16 944 945

118. CarverTJ

RutherfordKM

BerrimanM

RajandreamMA

BarrellBG

2005 ACT: the Artemis Comparison Tool. Bioinformatics 21 3422 3423