Evolutionary trade-offs underlie the multi-faceted virulence of staphylococcus aureus

Maisem Laabei, Anne-Catrin Uhlemann, Franklin D. Lowy, Eloise D. Austin, Maho Yokoyama, Khadija Ouadi, Edward Feil, Harry A. Thorpe, Barnabas G Williams, Mark Perkins, Sharon J. Peacock, Stephen R. Clarke, Janina Dordel, Matthew Holden, Antonina A. Votintseva, Rory Bowden, Derrick W. Crook, Bernadette C. Young, Daniel J. Wilson, Mario Recker & 1 others Ruth C. Massey

Research output: Contribution to journalArticle

46 Citations (Scopus)
40 Downloads (Pure)

Abstract

Bacterial virulence is a multifaceted trait where the interactions between pathogen and host factors affect the severity and outcome of the infection. Toxin secretion is central to the biology of many bacterial pathogens and is widely accepted as playing a crucial role in disease pathology. To understand the relationship between toxicity and bacterial virulence in greater depth, we studied two sequenced collections of the major human pathogen Staphylococcus aureus and found an unexpected inverse correlation between bacterial toxicity and disease severity. By applying a functional genomics approach, we identified several novel toxicity-affecting loci responsible for the wide range in toxic phenotypes observed within these collections. To understand the apparent higher propensity of low toxicity isolates to cause bacteraemia, we performed several functional assays, and our findings suggest that within-host fitness differences between high- and low-toxicity isolates in human serum is a contributing factor. As invasive infections, such as bacteraemia, limit the opportunities for onward transmission, highly toxic strains could gain an additional between-host fitness advantage, potentially contributing to the maintenance of toxicity at the population level. Our results clearly demonstrate how evolutionary trade-offs between toxicity, relative fitness, and transmissibility are critical for understanding the multifaceted nature of bacterial virulence.

Original languageEnglish
Article numbere1002229
Pages (from-to)1-21
Number of pages21
JournalPLoS Biology
Volume13
Issue number9
DOIs
Publication statusPublished - 2 Sep 2015

Fingerprint

Toxicity
Virulence
Staphylococcus aureus
virulence
Poisons
Bacteremia
toxicity
Host-Pathogen Interactions
Pathogens
Genomics
Infection
bacteremia
Maintenance
Pathology
Phenotype
pathogens
Serum
Population
infection
disease severity

Cite this

Laabei, M., Uhlemann, A-C., Lowy, F. D., Austin, E. D., Yokoyama, M., Ouadi, K., ... Massey, R. C. (2015). Evolutionary trade-offs underlie the multi-faceted virulence of staphylococcus aureus. PLoS Biology, 13(9), 1-21. [e1002229]. https://doi.org/10.1371/journal.pbio.1002229

Evolutionary trade-offs underlie the multi-faceted virulence of staphylococcus aureus. / Laabei, Maisem; Uhlemann, Anne-Catrin; Lowy, Franklin D.; Austin, Eloise D.; Yokoyama, Maho; Ouadi, Khadija; Feil, Edward; Thorpe, Harry A.; Williams, Barnabas G; Perkins, Mark; Peacock, Sharon J.; Clarke, Stephen R.; Dordel, Janina; Holden, Matthew; Votintseva, Antonina A.; Bowden, Rory; Crook, Derrick W.; Young, Bernadette C.; Wilson, Daniel J.; Recker, Mario; Massey, Ruth C.

In: PLoS Biology, Vol. 13, No. 9, e1002229, 02.09.2015, p. 1-21.

Research output: Contribution to journalArticle

Laabei, M, Uhlemann, A-C, Lowy, FD, Austin, ED, Yokoyama, M, Ouadi, K, Feil, E, Thorpe, HA, Williams, BG, Perkins, M, Peacock, SJ, Clarke, SR, Dordel, J, Holden, M, Votintseva, AA, Bowden, R, Crook, DW, Young, BC, Wilson, DJ, Recker, M & Massey, RC 2015, 'Evolutionary trade-offs underlie the multi-faceted virulence of staphylococcus aureus', PLoS Biology, vol. 13, no. 9, e1002229, pp. 1-21. https://doi.org/10.1371/journal.pbio.1002229
Laabei M, Uhlemann A-C, Lowy FD, Austin ED, Yokoyama M, Ouadi K et al. Evolutionary trade-offs underlie the multi-faceted virulence of staphylococcus aureus. PLoS Biology. 2015 Sep 2;13(9):1-21. e1002229. https://doi.org/10.1371/journal.pbio.1002229
Laabei, Maisem ; Uhlemann, Anne-Catrin ; Lowy, Franklin D. ; Austin, Eloise D. ; Yokoyama, Maho ; Ouadi, Khadija ; Feil, Edward ; Thorpe, Harry A. ; Williams, Barnabas G ; Perkins, Mark ; Peacock, Sharon J. ; Clarke, Stephen R. ; Dordel, Janina ; Holden, Matthew ; Votintseva, Antonina A. ; Bowden, Rory ; Crook, Derrick W. ; Young, Bernadette C. ; Wilson, Daniel J. ; Recker, Mario ; Massey, Ruth C. / Evolutionary trade-offs underlie the multi-faceted virulence of staphylococcus aureus. In: PLoS Biology. 2015 ; Vol. 13, No. 9. pp. 1-21.
@article{69d3f3636b2740ca80609d57fd7bbefe,
title = "Evolutionary trade-offs underlie the multi-faceted virulence of staphylococcus aureus",
abstract = "Bacterial virulence is a multifaceted trait where the interactions between pathogen and host factors affect the severity and outcome of the infection. Toxin secretion is central to the biology of many bacterial pathogens and is widely accepted as playing a crucial role in disease pathology. To understand the relationship between toxicity and bacterial virulence in greater depth, we studied two sequenced collections of the major human pathogen Staphylococcus aureus and found an unexpected inverse correlation between bacterial toxicity and disease severity. By applying a functional genomics approach, we identified several novel toxicity-affecting loci responsible for the wide range in toxic phenotypes observed within these collections. To understand the apparent higher propensity of low toxicity isolates to cause bacteraemia, we performed several functional assays, and our findings suggest that within-host fitness differences between high- and low-toxicity isolates in human serum is a contributing factor. As invasive infections, such as bacteraemia, limit the opportunities for onward transmission, highly toxic strains could gain an additional between-host fitness advantage, potentially contributing to the maintenance of toxicity at the population level. Our results clearly demonstrate how evolutionary trade-offs between toxicity, relative fitness, and transmissibility are critical for understanding the multifaceted nature of bacterial virulence.",
author = "Maisem Laabei and Anne-Catrin Uhlemann and Lowy, {Franklin D.} and Austin, {Eloise D.} and Maho Yokoyama and Khadija Ouadi and Edward Feil and Thorpe, {Harry A.} and Williams, {Barnabas G} and Mark Perkins and Peacock, {Sharon J.} and Clarke, {Stephen R.} and Janina Dordel and Matthew Holden and Votintseva, {Antonina A.} and Rory Bowden and Crook, {Derrick W.} and Young, {Bernadette C.} and Wilson, {Daniel J.} and Mario Recker and Massey, {Ruth C.}",
year = "2015",
month = "9",
day = "2",
doi = "10.1371/journal.pbio.1002229",
language = "English",
volume = "13",
pages = "1--21",
journal = "PLOS Biology",
issn = "1545-7885",
publisher = "Public Library of Science (PLOS)",
number = "9",

}

TY - JOUR

T1 - Evolutionary trade-offs underlie the multi-faceted virulence of staphylococcus aureus

AU - Laabei, Maisem

AU - Uhlemann, Anne-Catrin

AU - Lowy, Franklin D.

AU - Austin, Eloise D.

AU - Yokoyama, Maho

AU - Ouadi, Khadija

AU - Feil, Edward

AU - Thorpe, Harry A.

AU - Williams, Barnabas G

AU - Perkins, Mark

AU - Peacock, Sharon J.

AU - Clarke, Stephen R.

AU - Dordel, Janina

AU - Holden, Matthew

AU - Votintseva, Antonina A.

AU - Bowden, Rory

AU - Crook, Derrick W.

AU - Young, Bernadette C.

AU - Wilson, Daniel J.

AU - Recker, Mario

AU - Massey, Ruth C.

PY - 2015/9/2

Y1 - 2015/9/2

N2 - Bacterial virulence is a multifaceted trait where the interactions between pathogen and host factors affect the severity and outcome of the infection. Toxin secretion is central to the biology of many bacterial pathogens and is widely accepted as playing a crucial role in disease pathology. To understand the relationship between toxicity and bacterial virulence in greater depth, we studied two sequenced collections of the major human pathogen Staphylococcus aureus and found an unexpected inverse correlation between bacterial toxicity and disease severity. By applying a functional genomics approach, we identified several novel toxicity-affecting loci responsible for the wide range in toxic phenotypes observed within these collections. To understand the apparent higher propensity of low toxicity isolates to cause bacteraemia, we performed several functional assays, and our findings suggest that within-host fitness differences between high- and low-toxicity isolates in human serum is a contributing factor. As invasive infections, such as bacteraemia, limit the opportunities for onward transmission, highly toxic strains could gain an additional between-host fitness advantage, potentially contributing to the maintenance of toxicity at the population level. Our results clearly demonstrate how evolutionary trade-offs between toxicity, relative fitness, and transmissibility are critical for understanding the multifaceted nature of bacterial virulence.

AB - Bacterial virulence is a multifaceted trait where the interactions between pathogen and host factors affect the severity and outcome of the infection. Toxin secretion is central to the biology of many bacterial pathogens and is widely accepted as playing a crucial role in disease pathology. To understand the relationship between toxicity and bacterial virulence in greater depth, we studied two sequenced collections of the major human pathogen Staphylococcus aureus and found an unexpected inverse correlation between bacterial toxicity and disease severity. By applying a functional genomics approach, we identified several novel toxicity-affecting loci responsible for the wide range in toxic phenotypes observed within these collections. To understand the apparent higher propensity of low toxicity isolates to cause bacteraemia, we performed several functional assays, and our findings suggest that within-host fitness differences between high- and low-toxicity isolates in human serum is a contributing factor. As invasive infections, such as bacteraemia, limit the opportunities for onward transmission, highly toxic strains could gain an additional between-host fitness advantage, potentially contributing to the maintenance of toxicity at the population level. Our results clearly demonstrate how evolutionary trade-offs between toxicity, relative fitness, and transmissibility are critical for understanding the multifaceted nature of bacterial virulence.

U2 - 10.1371/journal.pbio.1002229

DO - 10.1371/journal.pbio.1002229

M3 - Article

VL - 13

SP - 1

EP - 21

JO - PLOS Biology

JF - PLOS Biology

SN - 1545-7885

IS - 9

M1 - e1002229

ER -