Evolutionary Trade-Offs Underlie the Multi-faceted Virulence of Staphylococcus aureus.
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.
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Maisem
M
Laabei
Department of Medicine, Columbia University, New York, New York, United States of America.
Anne-Catrin
AC
Uhlemann
Department of Medicine, Columbia University, New York, New York, United States of America.
Franklin D
FD
Lowy
Department of Medicine, Columbia University, New York, New York, United States of America.
Eloise D
ED
Austin
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Maho
M
Yokoyama
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Khadija
K
Ouadi
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Edward
E
Feil
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Harry A
HA
Thorpe
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Barnabas
B
Williams
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Mark
M
Perkins
Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Sharon J
SJ
Peacock
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom.
Stephen R
SR
Clarke
Pathogen Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Janina
J
Dordel
Pathogen Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; School of Medicine, Medical & Biological Sciences, North Haugh, St Andrews, Fife, United Kingdom.
Matthew
M
Holden
Nuffield Dept. of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Antonina A
AA
Votintseva
Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
Rory
R
Bowden
Nuffield Dept. of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Derrick W
DW
Crook
Nuffield Dept. of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Bernadette C
BC
Young
Nuffield Dept. of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
Daniel J
DJ
Wilson
Centre for Mathematics and the Environment, University of Exeter, Penryn Campus, Penryn, United Kingdom.
Mario
M
Recker
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Ruth C
RC
Massey
D016470:Bacteremia / Q000382:microbiology*; D018441:Biofilms; D005075:Biological Evolution; D065206:Extracellular Traps / Q000502:physiology; D023281:Genomics; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism; D011110:Polymorphism, Genetic; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D023084:alpha-Defensins
D023084:alpha-Defensins; D010447:Peptide Hydrolases