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 language | English |
|---|---|
| Article number | e1002229 |
| Pages (from-to) | 1-21 |
| Number of pages | 21 |
| Journal | PLoS Biology |
| Volume | 13 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2 Sep 2015 |
Fingerprint
Cite this
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 journal › Article
}
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 -