TY - JOUR
T1 - The micro-evolution and epidemiology of Staphylococcus aureus colonization during atopic eczema disease flare
AU - Harkins, Catriona
AU - Pettigrew, Kerry A
AU - Oravcová, Katarina
AU - Gardner, June
AU - Hearn, R. M. Ross
AU - Rice, Debbie
AU - Mather, Alison E
AU - Parkhill, Julian
AU - Brown, Sara
AU - Proby, Charlotte
AU - Holden, Matthew T. G.
N1 - The authors would like to thank the children and parents who participated in this research. We also thank Maeve McAleer, Orla Fleury, Timothy Foster, Désirée E. Bennett, Joan Geoghegan, Alan Irvine for their feedback on the project and critically reviewing the manuscript; and Ed Feil for useful discussions. C.P.H. was supported by Wellcome Trust [Grant number 104241/z/14/z]. M.T.G.H, K.A.P. and K.O. were supported by the Scottish Infection Research Network and Chief Scientist Office through the Scottish Healthcare Associated Infection Prevention Institute consortium funding [CSO Reference: SIRN10]. Bioinformatics and Computational Biology analyses were supported by the University of St Andrews Bioinformatics Unit that is funded by a Wellcome Trust ISSF award [grant MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT 16 097831/Z/11/Z]. J.P and M.T.G.H were supported by Wellcome Trust grant 098051. AEM is supported by Biotechnology and Biological Sciences Research Council grant BB/M014088/1. SJB is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science [106865/Z/15/Z].
PY - 2018/2
Y1 - 2018/2
N2 - Staphylococcus aureus is an opportunistic pathogen and variable component of the human microbiota. In atopic eczema (AE) a characteristic of the disease is colonization by S. aureus, with exacerbations associated with an increased bacterial burden of the organism. Despite this, the origins and genetic diversity of S. aureus colonizing individual patients during AE disease flares is poorly understood. To examine the micro-evolution of S. aureus colonization we have deep-sequenced S. aureus populations from nine children with moderate to severe AE, and 18 non-atopic children asymptomatically carrying S. aureus nasally. Colonization by clonal S. aureus populations was observed in both AE cases and controls, with all but one of the individuals containing colonies belonging to a single sequence type. Phylogenetic analysis revealed that disease flares were associated with the clonal expansion of the S. aureus population, occurring over a period of weeks to months. There was a significant difference in the genetic backgrounds of S. aureus colonizing AE patients versus controls (Fisher’s Exact test, p=0.03). Examination of intra-host genetic heterogeneity of the colonizing S. aureus populations identified evidence of within-host selection in the AE patients, with AE variants being potentially selectively advantageous for intracellular persistence and treatment resistance.
AB - Staphylococcus aureus is an opportunistic pathogen and variable component of the human microbiota. In atopic eczema (AE) a characteristic of the disease is colonization by S. aureus, with exacerbations associated with an increased bacterial burden of the organism. Despite this, the origins and genetic diversity of S. aureus colonizing individual patients during AE disease flares is poorly understood. To examine the micro-evolution of S. aureus colonization we have deep-sequenced S. aureus populations from nine children with moderate to severe AE, and 18 non-atopic children asymptomatically carrying S. aureus nasally. Colonization by clonal S. aureus populations was observed in both AE cases and controls, with all but one of the individuals containing colonies belonging to a single sequence type. Phylogenetic analysis revealed that disease flares were associated with the clonal expansion of the S. aureus population, occurring over a period of weeks to months. There was a significant difference in the genetic backgrounds of S. aureus colonizing AE patients versus controls (Fisher’s Exact test, p=0.03). Examination of intra-host genetic heterogeneity of the colonizing S. aureus populations identified evidence of within-host selection in the AE patients, with AE variants being potentially selectively advantageous for intracellular persistence and treatment resistance.
U2 - 10.1016/j.jid.2017.09.023
DO - 10.1016/j.jid.2017.09.023
M3 - Article
C2 - 28951239
SN - 0022-202X
VL - 138
SP - 336
EP - 343
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 2
ER -
