Genome Sequence of a Lancefield Group C Streptococcus zooepidemicus Strain Causing Epidemic Nephritis: New Information about an Old Disease

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

Ten-Year Follow-up of Patients with Epidemic Post Infectious Glomerulonephritis

BackgroundScarce information on outcomes of epidemic post infectious glomerulonephritis is available. This is a 10-year follow-up of the patients that developed acute glomerulonephritis in an epidemic outbreak caused by group C Streptococcus zooepidemicus in Brazil in 1998, that were also previously evaluated 2 and 5 years after the acute episode.MethodsIn this prospective study 60 cases (out of 134 in 1998) were reevaluated after 10 years, as well as community controls matched by gender and age. They underwent clinical and renal function evaluation, including serum creatinine and cystatin C, estimated glomerular filtration rate (eGFR), albuminuria and hematuria.ResultsComparisons of clinical and renal function aspects of 60 patients and 48 community controls have not shown significant differences (eGFR <60 ml/min/1.73m(2) and/or albuminuria >30mg/g creatinine: 13.8% vs. 12.2%, respectively, p = 0.817) except for a higher frequency of hypertension in the cases (45.0% vs. 20.8%, p = 0.009). Comparing the same patients affected in the acute episode, 2, 5 and 10 years later, it was observed an improvement of median eGFR levels at 2 years and a trend toward subsequent stabilization in these levels, associated with decrease in albuminuria and increased hypertension rates in the last survey. At 10 years it was not observed additional reduction of renal function using serum creatinine, eGFR and cystatin C.ConclusionsDuring the acute episode of epidemic GN a considerable proportion of patients presented hypertension and reduced renal function; after 2 years and particularly at this 10-year follow-up survey there was no worsening of renal function parameters, except for persistent higher frequency of hypertension. Nevertheless, a longer follow up is necessary to confirm that progressive loss of renal function will not occur

Comparison of the estimated GFR-creatinine values in the cases measured during the follow-up.

<p>Values are eGFR-creatinine (mL/min/1.73m²) expressed as median (interquartile range (IQR). The overall comparison between groups using the Friedman’s test was significant (p <0.001) and the multiple comparison tests (Wilcoxon’s test with Bonferroni’s correction (p level of significance: <0.020) yielded the following results for the pairwise comparisons: baseline vs. 2 yrs: p<0.001, baseline vs. 5 yrs: p = 0.005, baseline vs. 10 yrs: p<0.001; 2 yrs vs. 5 yrs: p = 0.835, 2 yrs vs. 10 yrs: 0.008; 5 yrs vs. 10 yrs: p<0.001.</p

Main findings in the Brazilian outbreak of <i>S</i>. <i>zooepidemicus</i> leading to PSGN along the years of follow-up.

<p>GFR, glomerular filtration rate; NA, not available.</p><p>^a creatinine clearance 2.</p><p>^b eGFR (MDRD equation) <60ml/min/1.73m².</p><p>^c12% considering >30 mg/g creatinine.</p><p>Additional data on reduced GFR: at onset 62% of the patients had serum creatinine >1.2 mg/dl; 11 patients required dialysis during the acute phase; 5 remained on chronic dialysis.</p><p>Main findings in the Brazilian outbreak of <i>S</i>. <i>zooepidemicus</i> leading to PSGN along the years of follow-up.</p

Gender, age, blood pressure and renal function parameters by group at 10-year follow-up.

<p>Values are N (%), mean±SD, or median (interquartile range).</p><p>Gender, age, blood pressure and renal function parameters by group at 10-year follow-up.</p

Previous reports of outbreaks of acute post streptococcal glomerulonephritis due to <i>S</i>. <i>zooepidemicus</i>.

<p>GN = glomerulonephritis.</p><p>*Dairy products have as primary source unpasteurized milk.</p><p>** Follow-up approach of the same outbreak (1998).</p><p>Previous reports of outbreaks of acute post streptococcal glomerulonephritis due to <i>S</i>. <i>zooepidemicus</i>.</p