Clonal Confinement of a Highly Mobile Resistance Element Driven by Combination Therapy in Rhodococcus equi

被引:24
作者
Alvarez-Narvaez, Sonsiray [1 ]
Giguere, Steeve [2 ]
Anastasi, Elisa [1 ]
Hearn, Jack [3 ]
Scortti, Mariela [1 ]
Vazquez-Boland, Jose A. [1 ]
机构
[1] Univ Edinburgh, Edinburgh Med Sch Biomed Sci, Microbial Pathogenesis Grp, Infect Med, Edinburgh, Midlothian, Scotland
[2] Univ Georgia, Dept Large Anim Med, Athens, GA 30602 USA
[3] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland
来源
MBIO | 2019年 / 10卷 / 05期
基金
英国生物技术与生命科学研究理事会;
关键词
ISRe46; MDR clonality; Rhodococcus equi; Rhodococcus equi MDR clone; Rhodococcus hoagii; Rhodococcus pneumonia; TnRErm46; erm(46); macrolide resistance; multidrug resistance; pRErm46; rifampin resistance; VIRULENCE PLASMID; ANTIMICROBIAL RESISTANCE; INTRACELLULAR SURVIVAL; STAPHYLOCOCCUS-AUREUS; PATHOGENICITY ISLAND; GLOBAL SPREAD; RPOB GENE; RIFAMPIN; EMERGENCE; EVOLUTION;
D O I
10.1128/mBio.02260-19
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Antibiotic use has been linked to changes in the population structure of human pathogens and the clonal expansion of multidrug-resistant (MDR) strains among healthcare- and community-acquired infections. Here we present a compelling example in a veterinary pathogen, Rhodococcus equi, the causative agent of a severe pulmonary infection affecting foals worldwide. We show that the erm(46) gene responsible for emerging macrolide resistance among equine R. equi isolates in the United States is part of a 6.9-kb transposable element, TnRErm46, actively mobilized by an IS481 family transposase. TnRErm46 is carried on an 87-kb conjugative plasmid, pRErm46, transferable between R. equi strains at frequencies up to 10(-3). The erm(46) gene becomes stabilized in R. equi by pRErm46's apparent fitness neutrality and wholesale TnRErm46 transposition onto the host genome. This includes the conjugally exchangeable pVAPA virulence plasmid, enabling the possibility of cotransfer of two essential traits for survival in macrolide-treated foals in a single mating event. Despite its high horizontal transfer potential, phylogenomic analyses show that erm(46) is paradoxically confined to a specific R. equi clone, 2287. R. equi 2287 also carries a unique rpoB(S531F) mutation conferring high-level resistance to rifampin, systematically administered together with macrolides against rhodococcal pneumonia on equine farms. Our data illustrate that under sustained combination therapy, several independent "founder" genetic events are concurrently required for resistance, limiting not only its emergence but also, crucially, horizontal spread, ultimately determining multiresistance clonality. IMPORTANCE MDR clades arise upon acquisition of resistance traits, but the determinants of their clonal expansion remain largely undefined. Taking advantage of the unique features of Rhodococcus equi infection control in equine farms, involving the same dual antibiotic treatment since the 1980s (a macrolide and rifampin), this study sheds light into the determinants of multiresistance clonality and the importance of combination therapy in limiting the dissemination of mobile resistance elements. Clinically effective therapeutic alternatives against R. equi foal pneumonia are currently lacking, and the identified macrolide-rifampin MDR clone 2287 has serious implications. Still at early stages of evolution and local spread, R. equi 2287 may disseminate globally, posing a significant threat to the equine industry and, also, public health due to the risk of zoonotic transmission. The characterization of the 2287 clone and its resistance determinants will enable targeted surveillance and control interventions to tackle the emergence of MDR R. equi.
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页数:17
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共 86 条
  • [51] INVITRO ANTIMICROBIAL SUSCEPTIBILITY OF RHODOCOCCUS-EQUI
    NORDMANN, P
    RONCO, E
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1992, 29 (04) : 383 - 393
  • [52] Molecular epidemiology of Rhodococcus equi based on traA, vapA, and vapB virulence plasmid markers
    Ocampo-Sosa, Alain A.
    Lewis, Deborah A.
    Navas, Jesus
    Quigley, Frances
    Callejo, Raquel
    Scortti, Mariela
    Leadon, Desmond P.
    Fogarty, Ursula
    Vazquez-Boland, Jose A.
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2007, 196 (05) : 763 - 769
  • [53] Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica
    Parkhill, J
    Sebaihia, M
    Preston, A
    Murphy, LD
    Thomson, N
    Harris, DE
    Holden, MTG
    Churcher, CM
    Bentley, SD
    Mungall, KL
    Cerdeño-Tárraga, AM
    Temple, L
    James, K
    Harris, B
    Quail, MA
    Achtman, M
    Atkin, R
    Baker, S
    Basham, D
    Bason, N
    Cherevach, I
    Chillingworth, T
    Collins, M
    Cronin, A
    Davis, P
    Doggett, J
    Feltwell, T
    Goble, A
    Hamlin, N
    Hauser, H
    Holroyd, S
    Jagels, K
    Leather, S
    Moule, S
    Norberczak, H
    O'Neil, S
    Ormond, D
    Price, C
    Rabbinowitsch, E
    Rutter, S
    Sanders, M
    Saunders, D
    Seeger, K
    Sharp, S
    Simmonds, M
    Skelton, J
    Squares, R
    Squares, S
    Stevens, K
    Unwin, L
    [J]. NATURE GENETICS, 2003, 35 (01) : 32 - 40
  • [54] Transposons Tn1696 and Tn21 and their integrons In4 and In2 have independent origins
    Partridge, SR
    Brown, HJ
    Stokes, HW
    Hall, RM
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (04) : 1263 - 1270
  • [55] Mycobacteriophage Lysin B is a novel mycolylarabinogalactan esterase
    Payne, Kimberly
    Sun, Qingan
    Sacchettini, James
    Hatfull, Graham F.
    [J]. MOLECULAR MICROBIOLOGY, 2009, 73 (03) : 367 - 381
  • [56] Evolution of AbaR-type genomic resistance islands in multiply antibiotic-resistant Acinetobacter baumannii
    Post, Virginia
    White, Peter A.
    Hall, Ruth M.
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2010, 65 (06) : 1162 - 1170
  • [57] RHODOCOCCUS-EQUI - AN ANIMAL AND HUMAN PATHOGEN
    PRESCOTT, JF
    [J]. CLINICAL MICROBIOLOGY REVIEWS, 1991, 4 (01) : 20 - 34
  • [58] FastTree 2-Approximately Maximum-Likelihood Trees for Large Alignments
    Price, Morgan N.
    Dehal, Paramvir S.
    Arkin, Adam P.
    [J]. PLOS ONE, 2010, 5 (03):
  • [59] MICs of 32 antimicrobial agents for Rhodococcus equi isolates of animal origin
    Riesenberg, Anne
    Fessler, Andrea T.
    Erol, Erdal
    Prenger-Berninghoff, Ellen
    Stamm, Ivonne
    Boese, Reinhard
    Heusinger, Anton
    Klarmann, Dieter
    Werckenthin, Christiane
    Schwarz, Stefan
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2014, 69 (04) : 1045 - 1049
  • [60] Genome and proteome analysis of phage E3 infecting the soil-borne actinomycete Rhodococcus equi
    Salifu, Samson P.
    Valero-Rello, Ana
    Campbell, Samantha A.
    Inglis, Neil F.
    Scortti, Mariela
    Foley, Sophie
    Vazquez-Boland, Jose A.
    [J]. ENVIRONMENTAL MICROBIOLOGY REPORTS, 2013, 5 (01): : 170 - 178