Abstract
Outbreaks of disease attributable to human error or natural causes can provide unique opportunities to gain new information about host-pathogen interactions and new leads for pathogenesis research. Poststreptococcal glomerulonephritis (PSGN), a sequela of infection with pathogenic streptococci, is a common cause of preventable kidney disease worldwide. Although PSGN usually occurs after infection with group A streptococci, organisms of Lancefield group C and G also can be responsible. Despite decades of study, the molecular pathogenesis of PSGN is poorly understood. As a first step toward gaining new information about PSGN pathogenesis, we sequenced the genome of Streptococcus equi subsp. zooepidemicus strain MGCS10565, a group C organism that caused a very large and unusually severe epidemic of nephritis in Brazil. The genome is a circular chromosome of 2,024,171 bp. The genome shares extensive gene content, including many virulence factors, with genetically related group A streptococci, but unexpectedly lacks prophages. The genome contains many apparently foreign genes interspersed around the chromosome, consistent with the presence of a full array of genes required for natural competence. An inordinately large family of genes encodes secreted extracellular collagen-like proteins with multiple integrin-binding motifs. The absence of a gene related to speB rules out the long-held belief that streptococcal pyrogenic exotoxin B or antibodies reacting with it singularly cause PSGN. Many proteins previously implicated in GAS PSGN, such as streptokinase, are either highly divergent in strain MGCS10565 or are not more closely related between these species than to orthologs present in other streptococci that do not commonly cause PSGN. Our analysis provides a comparative genomics framework for renewed appraisal of molecular events underlying APSGN pathogenesis.
Highlights
Epidemics of infectious disease attributable to human error or natural causes are unfortunate, such outbreaks can provide unique opportunities to gain new information about hostpathogen interactions and accelerated leads for pathogenesis research
There are only a few dozen reports of sporadic cases in the literature for the last 30 years [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. Organisms of this species have caused epidemic outbreaks of infection commonly associated with consumption of un- or inadequately pasteurized milk or milk products, and many of these epidemic outbreaks have been complicated with poststreptococcal glomerulonephritis (PSGN) [30,31,32,33,34,35,36,37,38]
In comparison to the major human pathogenic streptococcal species, the genome is modestly larger than genomes of group A Streptococcus pyogenes (GAS), and smaller than those of group B Streptococcus agalactiae (GBS) or Streptococcus pneumoniae
Summary
Epidemics of infectious disease attributable to human error or natural causes are unfortunate, such outbreaks can provide unique opportunities to gain new information about hostpathogen interactions and accelerated leads for pathogenesis research. S. equi subspecies zooepidemicus is primarily an opportunistic pathogen of a wide variety of non-human animal species, including important domesticated species such as horses, cows, pigs, sheep, and dogs, and as such is a pathogen of veterinary concern. It is a well-known cause of mastitis in cows and mares, and is the most frequently isolated opportunistic pathogen of horses [3]. Organisms of this species have caused epidemic outbreaks of infection commonly associated with consumption of un- or inadequately pasteurized milk or milk products, and many of these epidemic outbreaks have been complicated with poststreptococcal glomerulonephritis (PSGN) [30,31,32,33,34,35,36,37,38]
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