期刊论文详细信息
BMC Infectious Diseases
Longitudinal genetic analyses of Staphylococcus aureus nasal carriage dynamics in a diverse population
Alexander M Cole3  Christopher L Parkinson1  Sergio Tafur4  Alana B Persaud3  Vanathy Paramanandam3  Austin Ellis3  Ryan P Lamers2  Gowrishankar Muthukrishnan3 
[1]Department of Biology, University of Central Florida, 4000 Central Florida Boulevard, Orlando, FL, 32816, USA
[2]Current affiliation: Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
[3]Department of Molecular Biology and Microbiology, Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, 4000 Central Florida Boulevard, Orlando, FL, 32816, USA
[4]Stokes Advanced Research Computing Center, Institute for Simulation and Training, University of Central Florida, 3100 Technology Parkway, Orlando, FL, 32826, USA
关键词: SCCmec typing;    MRSA;    spa typing;    Nasal colonization;    Multi locus sequence typing;    Bacterial genetics;    Staphylococcus aureus;   
Others  :  1148394
DOI  :  10.1186/1471-2334-13-221
 received in 2012-12-10, accepted in 2013-05-08,  发布年份 2013
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【 摘 要 】

Background

Staphylococcus aureus (SA) nasal colonization plays a critical role in the pathogenesis of staphylococcal infections and SA eradication from the nares has proven to be effective in reducing endogenous infections. To understand SA nasal colonization and its relation with consequent disease, assessment of nasal carriage dynamics and genotypic diversity among a diverse population is a necessity.

Results

We have performed extensive longitudinal monitoring of SA nasal carriage isolates in 109 healthy individuals over a period of up to three years. Longitudinal sampling revealed that 24% of the individuals were persistent SA nasal carriers while 32% were intermittent. To assess the genetic relatedness between different SA isolates within our cohort, multi locus sequence typing (MLST) was performed. MLST revealed that not only were strains colonizing intermittent and persistent nasal carriers genetically similar, belonging to the same clonal complexes, but strain changes within the same host were also observed over time for both types of carriers. More highly discriminating genetic analyses using the hypervariable regions of staphylococcal protein A and clumping factor B virulence genes revealed no preferential colonization of specific SA strains in persistent or intermittent carriers. Moreover, we observed that a subset of persistent and intermittent carriers retained clinically relevant community-acquired methicillin-resistant SA (CA-MRSA) strains in their nares over time.

Conclusions

The findings of this study provides added perspective on the nasal carriage dynamics between strains colonizing persistent and intermittent carriers; an area currently in need of assessment given that persistent carriers are at greater risk of autoinfection than intermittent carriers.

【 授权许可】

   
2013 Muthukrishnan et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Chambers HF, Deleo FR: Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 2009, 7(9):629-641.
  • [2]Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM: Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 2007, 298(15):1763-1771.
  • [3]Kuehnert MJ, Kruszon-Moran D, Hill HA, McQuillan G, McAllister SK, Fosheim G, McDougal LK, Chaitram J, Jensen B, Fridkin SK: Prevalence of Staphylococcus aureus nasal colonization in the United States, 2001–2002. J Infect Dis 2006, 193(2):172-179.
  • [4]Lazo ND, Downing DT: A mixture of alpha-helical and 3(10)-helical conformations for involucrin in the human epidermal corneocyte envelope provides a scaffold for the attachment of both lipids and proteins. J Biol Chem 1999, 274(52):37340-37344.
  • [5]Steven AC, Steinert PM: Protein composition of cornified cell envelopes of epidermal keratinocytes. J Cell Sci 1994, 107(Pt 2):693-700.
  • [6]Williams RE: Healthy carriage of Staphylococcus aureus: its prevalence and importance. Bacteriol Rev 1963, 27:56-71.
  • [7]Weidenmaier C, Goerke C, Wolz C: Staphylococcus aureus determinants for nasal colonization. Trends Microbiol 2012, 20(5):243-250.
  • [8]Miller M, Cook HA, Furuya EY, Bhat M, Lee MH, Vavagiakis P, Visintainer P, Vasquez G, Larson E, Lowy FD: Staphylococcus aureus in the community: colonization versus infection. PLoS One 2009, 4(8):e6708.
  • [9]Wertheim HF, Melles DC, Vos MC, van Leeuwen W, van Belkum A, Verbrugh HA, Nouwen JL: The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis 2005, 5(12):751-762.
  • [10]Kluytmans J, van Belkum A, Verbrugh H: Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev 1997, 10(3):505-520.
  • [11]Wertheim HF, Vos MC, Ott A, van Belkum A, Voss A, Kluytmans JA, van Keulen PH, Vandenbroucke-Grauls CM, Meester MH, Verbrugh HA: Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet 2004, 364(9435):703-705.
  • [12]Eriksen NH, Espersen F, Rosdahl VT, Jensen K: Carriage of Staphylococcus aureus among 104 healthy persons during a 19-month period. Epidemiol Infect 1995, 115(1):51-60.
  • [13]Hu L, Umeda A, Kondo S, Amako K: Typing of Staphylococcus aureus colonising human nasal carriers by pulsed-field gel electrophoresis. J Med Microbiol 1995, 42(2):127-132.
  • [14]Nouwen JL, Fieren MW, Snijders S, Verbrugh HA, van Belkum A: Persistent (not intermittent) nasal carriage of Staphylococcus aureus is the determinant of CPD-related infections. Kidney Int 2005, 67(3):1084-1092.
  • [15]von Eiff C, Becker K, Machka K, Stammer H, Peters G: Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med 2001, 344(1):11-16.
  • [16]Robinson DA, Enright MC: Multilocus sequence typing and the evolution of methicillin-resistant Staphylococcus aureus. Clin Microbiol Infect 2004, 10(2):92-97.
  • [17]Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG: Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol 2000, 38(3):1008-1015.
  • [18]Feil EJ, Enright MC: Analyses of clonality and the evolution of bacterial pathogens. Curr Opin Microbiol 2004, 7(3):308-313.
  • [19]Shopsin B, Gomez M, Montgomery SO, Smith DH, Waddington M, Dodge DE, Bost DA, Riehman M, Naidich S, Kreiswirth BN: Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains. J Clin Microbiol 1999, 37(11):3556-3563.
  • [20]Harmsen D, Claus H, Witte W, Rothganger J, Claus H, Turnwald D, Vogel U: Typing of methicillin-resistant Staphylococcus aureus in a university hospital setting by using novel software for spa repeat determination and database management. J Clin Microbiol 2003, 41(12):5442-5448.
  • [21]Koreen L, Ramaswamy SV, Naidich S, Koreen IV, Graff GR, Graviss EA, Kreiswirth BN: Comparative sequencing of the serine-aspartate repeat-encoding region of the clumping factor B gene (clfB) for resolution within clonal groups of Staphylococcus aureus. J Clin Microbiol 2005, 43(8):3985-3994.
  • [22]Naas T, Fortineau N, Spicq C, Robert J, Jarlier V, Nordmann P: Three-year survey of community-acquired methicillin-resistant Staphylococcus aureus producing Panton-Valentine leukocidin in a French university hospital. J Hosp Infect 2005, 61(4):321-329.
  • [23]Daum RS, Ito T, Hiramatsu K, Hussain F, Mongkolrattanothai K, Jamklang M, Boyle-Vavra S: A novel methicillin-resistance cassette in community-acquired methicillin-resistant Staphylococcus aureus isolates of diverse genetic backgrounds. J Infect Dis 2002, 186(9):1344-1347.
  • [24]Suggs AH, Maranan MC, Boyle-Vavra S, Daum RS: Methicillin-resistant and borderline methicillin-resistant asymptomatic Staphylococcus aureus colonization in children without identifiable risk factors. Pediatr Infect Dis J 1999, 18(5):410-414.
  • [25]Naimi TS, LeDell KH, Como-Sabetti K, Borchardt SM, Boxrud DJ, Etienne J, Johnson SK, Vandenesch F, Fridkin S, O'Boyle C: Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA 2003, 290(22):2976-2984.
  • [26]Milheirico C, Oliveira DC, de Lencastre H: Update to the multiplex PCR strategy for assignment of mec element types in Staphylococcus aureus. Antimicrob Agents Chemother 2007, 51(9):3374-3377.
  • [27]Oliveira DC, de Lencastre H: Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2002, 46(7):2155-2161.
  • [28]Cole AM, Dewan P, Ganz T: Innate antimicrobial activity of nasal secretions. Infect Immun 1999, 67(7):3267-3275.
  • [29]Muthukrishnan G, Quinn GA, Lamers RP, Diaz C, Cole AL, Chen S, Cole AM: Exoproteome of Staphylococcus aureus reveals putative determinants of nasal carriage. J Proteome Res 2011, 10(4):2064-2078.
  • [30]Nashev D, Toshkova K, Salasia SI, Hassan AA, Lammler C, Zschock M: Distribution of virulence genes of Staphylococcus aureus isolated from stable nasal carriers. FEMS Microbiol Lett 2004, 233(1):45-52.
  • [31]Ruimy R, Angebault C, Djossou F, Dupont C, Epelboin L, Jarraud S, Lefevre LA, Bes M, Lixandru BE, Bertine M: Are host genetics the predominant determinant of persistent nasal Staphylococcus aureus carriage in humans? J Infect Dis 202(6):924-934.
  • [32]Wertheim HF, Walsh E, Choudhurry R, Melles DC, Boelens HA, Miajlovic H, Verbrugh HA, Foster T, van Belkum A: Key role for clumping factor B in Staphylococcus aureus nasal colonization of humans. PLoS Med 2008, 5(1):e17.
  • [33]Weidenmaier C, Kokai-Kun JF, Kristian SA, Chanturiya T, Kalbacher H, Gross M, Nicholson G, Neumeister B, Mond JJ, Peschel A: Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections. Nat Med 2004, 10(3):243-245.
  • [34]Weidenmaier C, Kokai-Kun JF, Kulauzovic E, Kohler T, Thumm G, Stoll H, Gotz F, Peschel A: Differential roles of sortase-anchored surface proteins and wall teichoic acid in Staphylococcus aureus nasal colonization. Int J Med Microbiol 2008, 298(5–6):505-513.
  • [35]Ferry T, Perpoint T, Vandenesch F, Etienne J: Virulence determinants in Staphylococcus aureus and their involvement in clinical syndromes. Curr Infect Dis Rep 2005, 7(6):420-428.
  • [36]Lamers RP, Stinnett JW, Muthukrishnan G, Parkinson CL, Cole AM: Evolutionary analyses of Staphylococcus aureus identify genetic relationships between nasal carriage and clinical isolates. PLoS One 2011, 6(1):e16426.
  • [37]VandenBergh MF, Yzerman EP, van Belkum A, Boelens HA, Sijmons M, Verbrugh HA: Follow-up of Staphylococcus aureus nasal carriage after 8 years: redefining the persistent carrier state. J Clin Microbiol 1999, 37(10):3133-3140.
  • [38]Huelsenbeck JP, Ronquist F: MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 2001, 17(8):754-755.
  • [39]Huelsenbeck JP, Ronquist F, Nielsen R, Bollback JP: Bayesian inference of phylogeny and its impact on evolutionary biology. Science 2001, 294(5550):2310-2314.
  • [40]Ronquist F, Huelsenbeck JP: MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 2003, 19(12):1572-1574.
  • [41]Posada D: jModelTest: phylogenetic model averaging. Mol Biol Evol 2008, 25(7):1253-1256.
  • [42]Hasegawa M, Iida Y, Yano T, Takaiwa F, Iwabuchi M: Phylogenetic relationships among eukaryotic kingdoms inferred from ribosomal RNA sequences. J Mol Evol 1985, 22(1):32-38.
  • [43]Feil EJ, Li BC, Aanensen DM, Hanage WP, Spratt BG: eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data. J Bacteriol 2004, 186(5):1518-1530.
  • [44]Spratt BG, Hanage WP, Li B, Aanensen DM, Feil EJ: Displaying the relatedness among isolates of bacterial species – the eBURST approach. FEMS Microbiol Lett 2004, 241(2):129-134.
  • [45]Sanger F, Nicklen S, Coulson AR: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 1977, 74(12):5463-5467.
  • [46]Gomes AR, Vinga S, Zavolan M, de Lencastre H: Analysis of the genetic variability of virulence-related loci in epidemic clones of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2005, 49(1):366-379.
  • [47]Gotelli NJ, Ellison AM: A. Primer Of Ecological Statistics: Sinauer Associates; 2004.
  • [48]Ni Eidhin D, Perkins S, Francois P, Vaudaux P, Hook M, Foster TJ: Clumping factor B (ClfB), a new surface-located fibrinogen-binding adhesin of Staphylococcus aureus. Mol Microbiol 1998, 30(2):245-257.
  • [49]Cole AM, Tahk S, Oren A, Yoshioka D, Kim YH, Park A, Ganz T: Determinants of Staphylococcus aureus nasal carriage. Clin Diagn Lab Immunol 2001, 8(6):1064-1069.
  • [50]Nouwen J, Boelens H, van Belkum A, Verbrugh H: Human factor in Staphylococcus aureus nasal carriage. Infect Immun 2004, 72(11):6685-6688.
  • [51]van Belkum A, Emonts M, Wertheim H, de Jongh C, Nouwen J, Bartels H, Cole A, Cole A, Hermans P, Boelens H: The role of human innate immune factors in nasal colonization by Staphylococcus aureus. Microbes Infect 2007, 9(12–13):1471-1477.
  • [52]Emonts M, Uitterlinden AG, Nouwen JL, Kardys I, Maat MP, Melles DC, Witteman J, Jong PT, Verbrugh HA, Hofman A: Host polymorphisms in interleukin 4, complement factor H, and C-reactive protein associated with nasal carriage of Staphylococcus aureus and occurrence of boils. J Infect Dis 2008, 197(9):1244-1253.
  • [53]Goslings WR, Buchli K: Nasal carrier rate of antibiotic-resistant staphylococci; influence of hospitalization on carrier rate in patients, and their household contacts. AMA Arch Intern Med 1958, 102(5):691-715.
  • [54]Nouwen JL, Ott A, Kluytmans-Vandenbergh MF, Boelens HA, Hofman A, van Belkum A, Verbrugh HA: Predicting the Staphylococcus aureus nasal carrier state: derivation and validation of a "culture rule". Clin Infect Dis Offic Publ Infect Dis Soc Am 2004, 39(6):806-811.
  • [55]Hidron AI, Low CE, Honig EG, Blumberg HM: Emergence of community-acquired meticillin-resistant Staphylococcus aureus strain USA300 as a cause of necrotising community-onset pneumonia. Lancet Infect Dis 2009, 9(6):384-392.
  • [56]King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM: Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med 2006, 144(5):309-317.
  • [57]Hofman A, Boerlage PA, Bots ML, Den Breeijen JH, De Bruijn AM, Grobbee DE, Hoes AW, De Jong PT, Koenders MJ, Odding E: [Prevalence of chronic diseases in the elderly; the ERGO study (Erasmus Rotterdam Health and the Elderly)]. Ned Tijdschr Geneeskd 1995, 139(39):1975-1978.
  • [58]Chen K, Pachter L: Bioinformatics for whole-genome shotgun sequencing of microbial communities. PLoS Comput Biol 2005, 1(2):106-112.
  • [59]Nashev D, Toshkova K, Bizeva L, Akineden O, Lammler C, Zschock M: Distribution of enterotoxin genes among carriage- and infection-associated isolates of Staphylococcus aureus. Lett Appl Microbiol 2007, 45(6):681-685.
  • [60]Van Belkum A, Riewarts Eriksen NH, Sijmons M, Van Leeuwen W, Van den Bergh M, Kluytmans J, Espersen F, Verbrugh H: Coagulase and protein A polymorphisms do not contribute to persistence of nasal colonisation by Staphylococcus aureus. J Med Microbiol 1997, 46(3):222-232.
  • [61]Nouwen J, Ott A, Boelens H, Van Belkum A, De Marie S, Verbrugh H: Smoking pattern and fasting glucose levels determine Staphylococcus aureus nasal carriage. Ph.D. Thesis. Rotterdam, The Netherlands: Erasmus University Medical Center; 2004.
  • [62]Bogaert D, van Belkum A, Sluijter M, Luijendijk A, de Groot R, Rumke HC, Verbrugh HA, Hermans PW: Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet 2004, 363(9424):1871-1872.
  • [63]Shinefield HR, Wilsey JD, Ribble JC, Boris M, Eichenwald HF, Dittmar CI: Interactions of staphylococcal colonization. Influence of normal nasal flora and antimicrobials on inoculated Staphylococcus aureus strain 502A. Am J Dis Child 1966, 111(1):11-21.
  • [64]Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, Agata T, Mizunoe Y: Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465(7296):346-349.
  • [65]Regev-Yochay G, Dagan R, Raz M, Carmeli Y, Shainberg B, Derazne E, Rahav G, Rubinstein E: Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in Children. JAMA 2004, 292(6):716-720.
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