TY - JOUR
T1 - Structure-function characterization of Streptococcus intermedius surface antigen pas
AU - Mieher, Joshua L.
AU - Schormann, Norbert
AU - Wu, Ren
AU - Patel, Manisha
AU - Purushotham, Sangeetha
AU - Wu, Hui
AU - Scoffield, Jessica
AU - Deivanayagam, Champion
N1 - Publisher Copyright:
© 2021 American Society for Microbiology. All Rights Reserved.
PY - 2021/10
Y1 - 2021/10
N2 - Streptococcus intermedius, an oral commensal bacterium, is found at various sites, including subgingival dental plaque, purulent infections, and cystic fibrosis lungs. Oral streptococci utilize proteins on their surface to adhere to tissues and/or surfaces localizing the bacteria, which subsequently leads to the development of biofilms, colonization, and infection. Among the 19 genomically annotated cell wall-attached surface proteins on S. intermedius, Pas is an adhesin that belongs to the antigen I/II (AgI/II) family. Here, we have structurally and functionally characterized Pas, particularly focusing on its microbial-host as well as microbial-microbial interactions. The crystal structures of VPas and C123Pas show high similarity with AgI/II of Streptococcus mutans. VPas hosts a conserved metal binding site, and likewise, the C123Pas structure retains its conserved metal binding sites and isopeptide bonds within its three DEv-IgG domains. Pas interacts with nanomolar affinity to lung alveolar glycoprotein 340 (Gp340), its scavenger receptor cysteine-rich domains (SRCRs), and with fibrinogen. Both Candida albicans and Pseudomonas aeruginosa, the opportunistic pathogens that cohabitate with S. intermedius in the lungs of CFTR patients were studied in dual-species biofilm studies. The Pas-deficient mutant (Dpas) displayed significant reduction in dual-biofilm formation with C. albicans. In similar studies with P. aeruginosa, Pas did not mediate the biofilm formation with either the acute isolate (PAO1) or the chronic isolate (FRD1). However, the sortase A-deficient mutant (DsrtA) displayed reduced biofilm formation with both C. albicans and P. aeruginosa FRD1. Taken together, our findings highlight the role of Pas in both microbial-host and interkingdom interactions and expose its potential role in disease outcomes.
AB - Streptococcus intermedius, an oral commensal bacterium, is found at various sites, including subgingival dental plaque, purulent infections, and cystic fibrosis lungs. Oral streptococci utilize proteins on their surface to adhere to tissues and/or surfaces localizing the bacteria, which subsequently leads to the development of biofilms, colonization, and infection. Among the 19 genomically annotated cell wall-attached surface proteins on S. intermedius, Pas is an adhesin that belongs to the antigen I/II (AgI/II) family. Here, we have structurally and functionally characterized Pas, particularly focusing on its microbial-host as well as microbial-microbial interactions. The crystal structures of VPas and C123Pas show high similarity with AgI/II of Streptococcus mutans. VPas hosts a conserved metal binding site, and likewise, the C123Pas structure retains its conserved metal binding sites and isopeptide bonds within its three DEv-IgG domains. Pas interacts with nanomolar affinity to lung alveolar glycoprotein 340 (Gp340), its scavenger receptor cysteine-rich domains (SRCRs), and with fibrinogen. Both Candida albicans and Pseudomonas aeruginosa, the opportunistic pathogens that cohabitate with S. intermedius in the lungs of CFTR patients were studied in dual-species biofilm studies. The Pas-deficient mutant (Dpas) displayed significant reduction in dual-biofilm formation with C. albicans. In similar studies with P. aeruginosa, Pas did not mediate the biofilm formation with either the acute isolate (PAO1) or the chronic isolate (FRD1). However, the sortase A-deficient mutant (DsrtA) displayed reduced biofilm formation with both C. albicans and P. aeruginosa FRD1. Taken together, our findings highlight the role of Pas in both microbial-host and interkingdom interactions and expose its potential role in disease outcomes.
KW - Candida albicans
KW - Protein structure-function
KW - Streptococcus intermedius
KW - Surface antigens
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U2 - 10.1128/JB.00175-21
DO - 10.1128/JB.00175-21
M3 - Article
C2 - 34339301
AN - SCOPUS:85115957653
SN - 0021-9193
VL - 203
JO - Journal of bacteriology
JF - Journal of bacteriology
IS - 20
M1 - e00175-21
ER -