Type-Specific Protection and Immunity Following Intranasal Inoculation of Monkeys With Group a Hemolytic Streptococci

Watson, Robin C.; Rothbard, Sidney; Swift, Homer F.

doi:10.1084/jem.84.2.127

Cited by 38 publications

(18 citation statements)

References 22 publications

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“…The GAS disease model in cynomolgus macaques probably provides the best demonstration of tonsillitis, following intranasal (IN) inoculation of live GAS [68,69]. Numerous studies have used nonhuman primate models for pharyngeal colonization and/or infection by GAS; however, high inoculating doses of bacteria are consistently employed, ranging from more than 3 × 10 5 to 10 8 CFU [68,70–73]. Nonetheless, transcription of several GAS genes that are upregulated in organisms recovered from pharyngitis patients are also expressed at elevated levels during infection in the macaque model [71].…”

Section: Animal Models For Gas Infection Of the Upper Respiratory Tractmentioning

confidence: 99%

Tissue Tropisms in Group a Streptococcal Infections

Bessen

Lizano

2010

Future Microbiol.

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Group A Streptococcus (GAS) is a human-specific pathogen that is highly prevalent throughout the world. The vast majority of GAS infections lead to a mild disease involving the epithelial surfaces of either the throat or skin. The concept of distinct sets of ‘throat’ and ‘skin’ strains of GAS has long been conceived. From an ecological standpoint, the epithelium of the throat and skin are important because it is where the organism is most successful in reproducing and transmitting to new hosts. This article examines key features of the epidemiology, population biology and molecular pathogenesis that underlie the tissue site preferences for infection exhibited by GAS, with an emphasis on work from our laboratory on skin tropisms. Recombinational replacement with orthologous gene forms, following interspecies transfer, appears to be an important genetic step leading up to the exploitation of new niches by GAS.

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Section: Animal Models For Gas Infection Of the Upper Respiratory Tractmentioning

confidence: 99%

Tissue Tropisms in Group a Streptococcal Infections

Bessen

Lizano

2010

Future Microbiol.

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“…On the basis of research conducted over decades, nonhuman primates are generally considered to be the most relevant animals for the study of experimental GAS pharyngitits (1,12,26,50,53,56,60). Although baboons (1) and rhesus macaques (53,56) have been colonized successfully in the upper respiratory tract with GAS, these animals did not develop clinical signs of acute pharyngitis.…”

Section: Figmentioning

confidence: 99%

Group AStreptococcusGene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis

Virtaneva¹,

Graham²,

Porcella³

et al. 2003

Infect Immun

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The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood. To provide new information about GAS host-pathogen interactions, we used real-time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis. The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component regulatory systems) was studied. Several known and previously uncharacterized GAS virulence gene regulators were highly expressed compared to the constitutively expressed control gene proS. To examine in vivo gene transcription in a controlled setting, three cynomolgus macaques were infected with strain MGAS5005, an organism that is genetically representative of most serotype M1 strains recovered from pharyngitis and invasive disease episodes in North America and Western Europe. These three animals developed clinical signs and symptoms of GAS pharyngitis and seroconverted to several GAS extracellular proteins. Real-time RT-PCR analysis of throat swab material collected at intervals throughout a 12-day infection protocol indicated that expression profiles of a subset of GAS genes accurately reflected the profiles observed in the human pediatric patients. The results of our study demonstrate that analysis of in vivo GAS gene expression is feasible in throat swab specimens obtained from infected human and nonhuman primates. In addition, we conclude that the cynomolgus macaque is a useful nonhuman primate model for the study of molecular events contributing to acute pharyngitis caused by GAS.

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“…By virtue of similar phylogeny, it is reasonable to expect that nonhuman primates would be a more appropriate host than rodents for modelling human throat infection and throat colonization. Indeed, work several decades ago indicated that GAS persisted in the throat of non-human primates after oral inoculation and that these infections led to the development of characteristic humoral immune responses, including protective type-specific anti-M protein antibody (Watson et al, 1946;Vanace, 1960;Taranta et al, 1969;Zimmerman et al, 1970).…”

Section: Introductionmentioning

confidence: 99%