Assessment of Cpa, Scl1 and Scl2 in clinical group A streptococcus isolates and patients from north India: an evaluation of the host pathogen interaction

Chaudhary, Priyanka; Kumar, Rajesh; Sagar, Vivek; Sarkar, Subendu; Singh, Raman; Ghosh, Sujata; Singh, Surjit; Chakraborti, Anuradha

doi:10.1016/j.resmic.2017.09.002

Cited by 4 publications

(6 citation statements)

References 40 publications

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“…In serotypes with distinct-virulence, expressed-adhesins Scl1, Scl2 reflect semblance in domain-structures and we found assertive homology with variations in certain primary aa sequence and (in) number of CL-repeats, as also reported in earlier characterizations [23]. This essentially corroborates our previous observations where we deciphered ubiquity of Scls among GAS serotypes [11]. Multiple sequence alignment of the GAS M1 and M49 Scl1 proteins show 77% sequence identity, but M49-Scl1 has a 63-residue insertion at the end of the CL-domain, which is not present in M1-Scl1.…”

Section: Discussionsupporting

confidence: 91%

“…In the similar context, emphasizing their essential roles in GAS pathogenesis, in our previous studies, we found conservation of Scls among 27 emm types identified in clinical-GAS isolates [11]. Many microbial species carry collagen-like (CL) sequences in their genome, among these, streptococcal-proteins received more evaluation in the last decade.…”

Section: Discussionmentioning

confidence: 83%

“…Recently, bacteria have been found to carry collagen-like sequences, whereby only few express these [7][8][9][10]. In our previous-studies, homology and conservation of these genes were recognized with 100% expression in group A streptococcus (GAS)-strains from 27 emm types [11]. Our another-study identified M1-2 (emm1-2 serotype), an M1 variant, emerging in northern India; its sequence and annotation is recently updated [12].…”

Section: Introductionmentioning

confidence: 82%

“…The enhanced pathogenic-potential of GAS is mediated through the ensemble of many virulent-markers, most important are adhesins which define primarily fate of the assault as mediators in initial stages of establishment of infection. Recently, the streptococcal collagen-like proteins (Scls) have given insights toward novel potential pathogenic-adhesins of GAS mediating internalization through matrix interaction [38], [39], associated human tissue-protein cryptic-interactions, i.e., collagen types I and IV cross-reactivity, and a sero-positive [11], among its important pathogenic facets.…”

Section: Discussionmentioning

confidence: 99%

“…Scls (proteins) are among cardinal adhesins recently identified in genomes of most GASstrains and are highly conserved, show distinct interaction with human-major collagens [11], mediated through specific mechanisms [38][39][40]. In context of these observations, we hypothesized/speculated to characterize Scls from GAS-strains with varied virulence towards similarities, with emphasis on their collagenous-domains.…”

Section: Recombinant Constructs Of Streptococcal Collagen-like Protein Sclsmentioning

confidence: 99%

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Synergistic collagen-condiment: Streptococcal collagen-like (Scl) protein in cell-adhesion and diabetic wound-closure matrix

Singh

Choudhury

Nambiyar

et al. 2021

Preprint

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Group A streptococcus (GAS), Streptococcus pyogenes manifests plethora of diseases through its explicit virulence factors. Among these, the recently deciphered MSCRAMMs, Streptococcal collagen-like (Scls) adhesins are most studied proteins in context of their biophysically stable collagenous-sequence (Gly-X-Y) despite the difference from analogous mammalian-collagen. Based on recent evidence on collagen-mimetic Scls, we elucidated biomaterial-potential of the unmodified, recombinant Scl1 (rScl1). Initially, rScl1 trimeric- assembly yielded its stability in silico than the monomeric-unit. Thereby, rScl1 matrix characterization was confirmed in vitro. rScl1 exhibited high A549 and HepG2 cell- viability—rScl1 dose incremented to 20.0 µg/ml at time points up to 24 hr, and on 24 hr stored-dishes—deliberating it non-cytotoxic. Imploring cell-adhesion potential, we observed increased cell-counts tangential to rScl1-gradient. This affirmative prelude on rScl1 as a supporting-matrix cued its synergy to collagen; we discerned it through rScl1-augmented, full-thickness diabetic wound-closure in vivo and as a first, we studied > 18-month rabbit alloxan-models. We have ascertained re-epithelialization with higher type III collagen in absence of inflammation evidenced morphometrically and histologically. Finally, we correlated our observations through atomistic-evaluation of rScl1-α2β1-integrin interaction, surprisingly, with augmented binding-energy compared to collagen. Hence, connoting recombinant-streptococcal collagen as an ‘alternate’; with further characterization, rScl1 can potentiate important revelations conceding homogeneous and safe, bio-available, biomaterial.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Recombinant Constructs Of Streptococcal Collagen-like Protein Sclsmentioning

confidence: 99%

See 3 more Smart Citations

Synergistic collagen-condiment: Streptococcal collagen-like (Scl) protein in cell-adhesion and diabetic wound-closure matrix

Singh

Choudhury

Nambiyar

et al. 2021

Preprint

Self Cite

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Streptococcal Collagen-like Protein 1 Binds Wound Fibronectin: Implications in Pathogen Targeting

McNitt

Water

Marasco

et al. 2019

CMC

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Group A Streptococcus (GAS) infections are responsible for significant morbidity and mortality worldwide. The outlook for an effective global vaccine is reduced because of significant antigenic variation among GAS strains worldwide. Other challenges in GAS therapy include the lack of common access to antibiotics in developing countries, as well as allergy to and treatment failures with penicillin and increasing erythromycin resistance in the industrialized world. At the portal of entry, GAS binds to newly deposited extracellular matrix, which is rich in cellular fibronectin isoforms with extra domain A (EDA, also termed EIIIA) via the surface adhesin, the streptococcal collagen-like protein 1 (Scl1). Recombinant Scl1 constructs, derived from diverse GAS strains, bind the EDA loop segment situated between the C and C' β-strands. Despite the sequence diversity in Scl1 proteins, multiple sequence alignments and secondary structure predictions of Scl1 variants, as well as crystallography and homology modeling studies, point to a conserved mechanism of Scl1-EDA binding. We propose that targeting this interaction may prevent the progression of infection. A synthetic cyclic peptide, derived from the EDA C-C' loop, binds to recombinant Scl1 with a micromolar dissociation constant. This review highlights the current concept of EDA binding to Scl1 and provides incentives to exploit this binding to treat GAS infections and wound colonization.

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Case Report: Septic arthritis in children caused by Streptococcus pyogenes–rational use of antibiotics

Gao

Guo

et al. 2023

Front. Cell. Infect. Microbiol.

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To investigate the clinical characteristics and treatment of septic arthritis caused by Streptococcus pyogenes(S. pyogenes) in children, we retrospectively analyzed the clinical data, laboratory results, treatments and outcomes of three pediatric cases of septic arthritis caused by S. pyogenes occurring from 2016–2018. The three cases of septic arthritis included 1 boy and 2 girls, aged from 2–7 years. Two patients experienced fever, and in all three cases, the affected joints showed redness, swelling, an increased local skin temperature, tenderness and restricted limb movement. At the first visit, all three cases showed a significantly increased white blood cell count [(27.68–32.02)×109/mL] and a significantly increased erythrocyte sedimentation rate (113–134 mm/h). The C-reactive protein level was significantly increased in two cases (67 mg/L, 147.7 mg/L) and normal in one case. The procalcitonin level was normal in 1 case, elevated in 1 case, and undetected in 1 case. S. pyogenes isolated from cases 1 and 2 were emm1/ST28 and from case 3 was emm12/ST36. All patients were treated by abscess incision and drainage, and S. pyogenes was cultured in the abscess puncture fluid. All patients were treated with intravenous antibiotics after admission, and all patients were cured and discharged. The patients were followed up for 2 months, and their condition was improved and stable. No sequelae such as heart and kidney damage were detected. In conclusion, for children with septic arthritis, early diagnosis and timely treatment with incision and drainage followed by culture of the abscess puncture fluid are important. Once S. pyogenes infection is confirmed, β-lactam antibiotics provide effective treatment, avoiding use of broad-spectrum antibiotics.

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Assessment of Cpa, Scl1 and Scl2 in clinical group A streptococcus isolates and patients from north India: an evaluation of the host pathogen interaction

Cited by 4 publications

References 40 publications

Synergistic collagen-condiment: Streptococcal collagen-like (Scl) protein in cell-adhesion and diabetic wound-closure matrix

Synergistic collagen-condiment: Streptococcal collagen-like (Scl) protein in cell-adhesion and diabetic wound-closure matrix

Streptococcal Collagen-like Protein 1 Binds Wound Fibronectin: Implications in Pathogen Targeting

Case Report: Septic arthritis in children caused by Streptococcus pyogenes–rational use of antibiotics

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