SufA – a novel subtilisin-like serine proteinase of Finegoldia magna

Karlsson, Christofer; Andersson, Michael; Collin, Mattias; Schmidtchen, Artur; Björck, Lars; Frick, Inga-Maria

doi:10.1099/mic.0.2007/010322-0

Cited by 41 publications

(64 citation statements)

References 57 publications

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“…Dentilisin is used by the oral spirochete Treponema denticola to degrade host chemokines, cytokines, and fibrinogen (4,45) and to rearrange the bacterial outer sheath (26). SufA, encoded by the Gram-positive bacterium Finegoldia magna (an opportunistic pathogen of humans), inactivates antimicrobial peptides and chemokines and is believed to aid in bacterial survival in the host (29).…”

Section: Resultsmentioning

confidence: 99%

Comparative Genomic Analyses of Attenuated Strains of Mycoplasma gallisepticum

et al. 2010

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Mycoplasma gallisepticum is a significant respiratory and reproductive pathogen of domestic poultry. While the complete genomic sequence of the virulent, low-passage M. gallisepticum strain R (R low ) has been reported, genomic determinants responsible for differences in virulence and host range remain to be completely identified. Here, we utilize genome sequencing and microarray-based comparative genomic data to identify these genomic determinants of virulence and to elucidate genomic variability among strains of M. gallisepticum. Analysis of the high-passage, attenuated derivative of R low , R high , indicated that relatively few total genomic changes (64 loci) occurred, yet they are potentially responsible for the observed attenuation of this strain. In addition to previously characterized mutations in cytadherence-related proteins, changes included those in coding sequences of genes involved in sugar metabolism. Analyses of the genome of the M. gallisepticum vaccine strain F revealed numerous differences relative to strain R, including a highly divergent complement of vlhA surface lipoprotein genes, and at least 16 genes absent or significantly fragmented relative to strain R. Notably, an R low isogenic mutant in one of these genes (MGA_1107) caused significantly fewer severe tracheal lesions in the natural host compared to virulent M. gallisepticum R low . Comparative genomic hybridizations indicated few genetic loci commonly affected in F and vaccine strains ts-11 and 6/85, which would correlate with proteins affecting strain R virulence. Together, these data provide novel insights into inter-and intrastrain M. gallisepticum genomic variability and the genetic basis of M. gallisepticum virulence.

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Section: Resultsmentioning

confidence: 99%

Comparative Genomic Analyses of Attenuated Strains of Mycoplasma gallisepticum

et al. 2010

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“…Antimicrobial peptides are produced both constitutively and in response to infection by epithelial cells and neutrophils in the genital tract (38)(39)(40). Many bacterial species have been selected to evolve strategies for evading AMPs via releasing soluble factors to trap (41,42) or degrade the antimicrobial peptides (15)(16)(17)43). The intrainclusion C. trachomatis organisms are known to secrete various proteins, including CPAF and Pgp3, into host cell cytosol (2,20,33,(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Chlamydial Plasmid-Encoded Virulence Factor Pgp3 Neutralizes the Antichlamydial Activity of Human Cathelicidin LL-37

et al. 2015

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dChlamydia trachomatis infection in the lower genital tract can ascend to and cause pathologies in the upper genital tract, potentially leading to severe complications, such as tubal infertility. However, chlamydial organisms depleted of plasmid or deficient in the plasmid-encoded Pgp3 are attenuated in ascending infection and no longer are able to induce the upper genital tract pathologies, indicating a significant role of Pgp3 in chlamydial pathogenesis. We now report that C. trachomatis Pgp3 can neutralize the antichlamydial activity of human cathelicidin LL-37, a host antimicrobial peptide secreted by both genital tract epithelial cells and infiltrating neutrophils. Pgp3 bound to and formed stable complexes with LL-37. We further showed that the middle region of Pgp3 (Pgp3m) was responsible for both the binding to and neutralization of LL-37, suggesting that Pgp3m can be targeted for attenuating chlamydial pathogenicity or developed for blocking LL-37-involved non-genital-tract pathologies, such as rosacea and psoriasis. Thus, the current study has provided significant information for both understanding the mechanisms of chlamydial pathogenesis and developing novel therapeutic agents. Chlamydia trachomatis infection in women's lower genital tract can ascend to and cause inflammatory pathologies in the upper genital tract, resulting in complications such as ectopic pregnancy and tubal infertility (1, 2). However, the mechanisms of how the C. trachomatis organisms ascend to the upper genital tract remain unknown. It is thought that the organisms' ability to complete intracellular replication and to spread from cell to cell significantly contributes to chlamydial pathogenicity (3-6). Chlamydial intracellular infection starts with the entry of an infectious elementary body (EB) into an epithelial cell via pathogen-induced endocytosis (7,8). The endocytosed EB differentiates to a noninfectious but metabolically active reticulate body (RB). After replication, the progeny RBs differentiate back to EBs that exit the infected cells to invade adjacent cells (6). The spreading from cell to cell inevitably exposes the progeny EBs to the extracellular mucosal environment, in which numerous host defense molecules, such as antimicrobial peptides (AMPs), are available for attacking the extracellular EBs. It is unclear how the C. trachomatis EB organisms manage to overcome these host defense mechanisms to ascend to the upper genital tract.Cationic peptides that possess antimicrobial activities are defined as AMPs, which include human alpha-defensins (HADs) or human neutrophil peptides (HNPs), human beta-defensins (HBDs), and cathelicidin LL-37 (9-12). LL-37 is a C-terminal 37-amino-acid peptide starting with double leucines (LL) processed from human cationic antimicrobial protein 18 (hCAP; 18 kDa) that contains a highly conserved amino-terminal cathelinlike domain and a variable carboxy-terminal domain (9, 11). The mouse orthologue is called cathelin-related antimicrobial peptide (CRAMP) (13). HNPs are produced mainly by neu...

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“…Native SufA and SpeB were purified as previously described (13,28). Recombinantly expressed protein FAF (aa 28-616) was obtained as a fusion protein with GST as described (12).…”

Section: Proteins and Peptidesmentioning

confidence: 99%

“…It is therefore likely that F. magna encounter the constitutively expressed AMPs MK and BRAK/CXCL14 during normal, noninflamed conditions. Most strains of F. magna express a subtilisin-like enzyme, subtilase of F. magna (SufA), which is associated with the bacterial surface (13). Both FAF and SufA are produced at substantial amounts during early logarithmic phase, and, in addition to being surface associated, they are released to the environment (12,13).…”

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confidence: 99%

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Constitutive and Inflammation-Dependent Antimicrobial Peptides Produced by Epithelium Are Differentially Processed and Inactivated by the Commensal Finegoldia magna and the Pathogen Streptococcus pyogenes

Frick

Nordin

Baumgarten

et al. 2011

The Journal of Immunology

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Epithelial linings serve as physical barriers and produce antimicrobial peptides (AMPs) to maintain host integrity. Examples are the bactericidal proteins midkine (MK) and BRAK/CXCL14 that are constitutively produced in the skin epidermal layer, where the anaerobic Gram-positive coccoid commensal Finegoldia magna resides. Consequently, this bacterium is likely to encounter both MK and BRAK/CXCL14, making these molecules possible threats to its habitat. In this study, we show that MK expression is upregulated during inflammation, concomitant with a strong downregulation of BRAK/CXCL14, resulting in changed antibacterial conditions. MK, BRAK/CXCL14, and the inflammation-dependent antimicrobial β-defensins human β-defensin (hBD)-2 and hBD-3 all showed bactericidal activity against both F. magna and the virulent pathogen Streptococcus pyogenes at similar concentrations. SufA, a released protease of F. magna, degraded MK and BRAK/CXCL14 but not hBD-2 nor hBD-3. Cleavage was seen at lysine and arginine residues, amino acids characteristic of AMPs. Intermediate SufA-degraded fragments of MK and BRAK/CXCL14 showed stronger bactericidal activity against S. pyogenes than F. magna, thus promoting survival of the latter. In contrast, the cysteine-protease SpeB of S. pyogenes rapidly degraded all AMPs investigated. The proteins FAF and SIC, released by F. magna and S. pyogenes, respectively, neutralized the antibacterial activity of MK and BRAK/CXCL14, protein FAF being the most efficient. Quantitation and colocalization by immunoelectron microscopy demonstrated significant levels and interactions of the molecules in in vivo and ex vivo samples. The findings reflect strategies used by a permanently residing commensal and a virulent pathogen, the latter operating during the limited time course of invasive disease.

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SufA – a novel subtilisin-like serine proteinase of Finegoldia magna

Cited by 41 publications

References 57 publications

Comparative Genomic Analyses of Attenuated Strains of Mycoplasma gallisepticum

Comparative Genomic Analyses of Attenuated Strains of Mycoplasma gallisepticum

Chlamydial Plasmid-Encoded Virulence Factor Pgp3 Neutralizes the Antichlamydial Activity of Human Cathelicidin LL-37

Constitutive and Inflammation-Dependent Antimicrobial Peptides Produced by Epithelium Are Differentially Processed and Inactivated by the Commensal Finegoldia magna and the Pathogen Streptococcus pyogenes

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