Emergence of a bacterial clone with enhanced virulence by acquisition of a phage encoding a secreted phospholipase A2.
The molecular basis of pathogen clone emergence is relatively poorly understood. Acquisition of a bacteriophage encoding a previously unknown secreted phospholipase A(2) (designated SlaA) has been implicated in the rapid emergence in the mid-1980s of a new hypervirulent clone of serotype M3 group A Streptococcus. Although several lines of circumstantial evidence suggest that SlaA is a virulence factor, this issue has not been addressed experimentally. We found that an isogenic DeltaslaA mutant strain was significantly impaired in ability to adhere to and kill human epithelial cells compared with the wild-type parental strain. The mutant strain was less virulent for mice than the wild-type strain, and immunization with purified SlaA significantly protected mice from invasive disease. Importantly, the mutant strain was significantly attenuated for colonization in a monkey model of pharyngitis. We conclude that transductional acquisition of the ability of a GAS strain to produce SlaA enhanced the spread and virulence of the serotype M3 precursor strain. Hence, these studies identified a crucial molecular event underlying the evolution, rapid emergence, and widespread dissemination of unusually severe human infections caused by a distinct bacterial clone.
Sitkiewicz
Izabela
I
Center for Molecular and Translational Human Infectious Diseases Research, Methodist Hospital Research Institute, Houston, TX 77030, USA.
Nagiec
Michal J
MJ
Sumby
Paul
P
Butler
Stephanie D
SD
Cywes-Bentley
Colette
C
Musser
James M
JM
D000818:Animals; D001435:Bacteriophages / Q000235:genetics* / Q000472:pathogenicity; D002478:Cells, Cultured; D006801:Humans; D007114:Immunization; D008297:Male; D008561:Membrane Fusion; D051379:Mice; D010741:Phospholipases A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054467:Phospholipases A2; D012141:Respiratory Tract Infections / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D013290:Streptococcal Infections / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D013291:Streptococcus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D015996:Survival Rate
D010741:Phospholipases A; D054467:Phospholipases A2