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Streptococcus pyogenes genes that promote pharyngitis in primates
Luchang Zhu, … , Frank R. DeLeo, James M. Musser
Luchang Zhu, … , Frank R. DeLeo, James M. Musser
Published June 4, 2020
Citation Information: JCI Insight. 2020;5(11):e137686. https://doi.org/10.1172/jci.insight.137686.
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Research Article Infectious disease

Streptococcus pyogenes genes that promote pharyngitis in primates

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Abstract

Streptococcus pyogenes (group A streptococcus; GAS) causes 600 million cases of pharyngitis annually worldwide. There is no licensed human GAS vaccine despite a century of research. Although the human oropharynx is the primary site of GAS infection, the pathogenic genes and molecular processes used to colonize, cause disease, and persist in the upper respiratory tract are poorly understood. Using dense transposon mutant libraries made with serotype M1 and M28 GAS strains and transposon-directed insertion sequencing, we performed genome-wide screens in the nonhuman primate (NHP) oropharynx. We identified many potentially novel GAS fitness genes, including a common set of 115 genes that contribute to fitness in both genetically distinct GAS strains during experimental NHP pharyngitis. Targeted deletion of 4 identified fitness genes/operons confirmed that our newly identified targets are critical for GAS virulence during experimental pharyngitis. Our screens discovered many surface-exposed or secreted proteins — substrates for vaccine research — that potentially contribute to GAS pharyngitis, including lipoprotein HitA. Pooled human immune globulin reacted with purified HitA, suggesting that humans produce antibodies against this lipoprotein. Our findings provide new information about GAS fitness in the upper respiratory tract that may assist in translational research, including developing novel vaccines.

Authors

Luchang Zhu, Randall J. Olsen, Stephen B. Beres, Matthew Ojeda Saavedra, Samantha L. Kubiak, Concepcion C. Cantu, Leslie Jenkins, Andrew S. Waller, Zhizeng Sun, Timothy Palzkill, Adeline R. Porter, Frank R. DeLeo, James M. Musser

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Figure 1

TraDIS analysis of GAS genes contributing to primate URT infection.

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TraDIS analysis of GAS genes contributing to primate URT infection.
(A) ...
(A) Comparison of M1 and M28 GAS genes contributing to fitness in the NHP URT. (B) Comparison of GAS genes required in the NHP URT and those important for NHP necrotizing fasciitis (NF). Representative fitness genes assigned to each category are shown. Genes selected for further validation and investigation are highlighted in red.

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