scholarly journals Septal secretion of protein A in Staphylococcus aureus requires SecA and lipoteichoic acid synthesis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Wenqi Yu ◽  
Dominique Missiakas ◽  
Olaf Schneewind
Keyword(s):  
Staphylococcus Aureus ◽  
Signal Peptide ◽  
Protein A ◽  
Lipoteichoic Acid ◽  
Acid Synthesis ◽  
Surface Proteins ◽  
Cross Wall ◽  
Staphylococcal Protein A ◽  
The Cross ◽  
Wall Depletion

Surface proteins of Staphylococcus aureus are secreted across septal membranes for assembly into the bacterial cross-wall. This localized secretion requires the YSIRK/GXXS motif signal peptide, however the mechanisms supporting precursor trafficking are not known. We show here that the signal peptide of staphylococcal protein A (SpA) is cleaved at the YSIRK/GXXS motif. A SpA signal peptide mutant defective for YSIRK/GXXS cleavage is also impaired for septal secretion and co-purifies with SecA, SecDF and LtaS. SecA depletion blocks precursor targeting to septal membranes, whereas deletion of secDF diminishes SpA secretion into the cross-wall. Depletion of LtaS blocks lipoteichoic acid synthesis and abolishes SpA precursor trafficking to septal membranes. We propose a model whereby SecA directs SpA precursors to lipoteichoic acid-rich septal membranes for YSIRK/GXXS motif cleavage and secretion into the cross-wall.

scholarly journals Septal Secretion of Protein A inStaphylococcus aureusRequires SecA and Lipoteichoic Acid Synthesis

2018 ◽  
Author(s):  
Wenqi Yu ◽  
Dominique Missiakas ◽  
Olaf Schneewind
Keyword(s):  
Staphylococcus Aureus ◽  
Signal Peptide ◽  
Protein A ◽  
Lipoteichoic Acid ◽  
Acid Synthesis ◽  
Surface Proteins ◽  
Cross Wall ◽  
Staphylococcal Protein A ◽  
The Cross ◽  
Wall Depletion

AbstractSurface proteins ofStaphylococcus aureusare secreted across septal membranes for assembly into the bacterial cross-wall. This localized secretion requires the YSIRK/GXXS motif signal peptide, however the mechanisms supporting precursor trafficking are not known. We show here that the signal peptide of staphylococcal protein A (SpA) is cleaved at the YSIRK/GXXS motif. A signal peptide mutant defective for cleavage can be crosslinked to SecA, SecDF and LtaS. SecA depletion blocks precursor targeting to septal membranes, whereas deletion ofsecDFdiminishes SpA secretion into the cross-wall. Depletion of LtaS blocks lipoteichoic acid synthesis and promotes precursor trafficking to peripheral membranes. We propose a model whereby SecA directs SpA precursors to lipoteichoic acid-rich septal membranes for YSIRK/GXXS motif cleavage and secretion into the cross-wall.

scholarly journals Rapid and Broad Immune Efficacy of a Recombinant Five-Antigen Vaccine against Staphylococcus aureus Infection in Animal Models

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 134 ◽  
Author(s):  
Hao Zeng ◽  
Feng Yang ◽  
Qiang Feng ◽  
Jinyong Zhang ◽  
Jiang Gu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Severe Disease ◽  
Lethal Dose ◽  
Protein A ◽  
Surface Proteins ◽  
Staphylococcal Protein A ◽  
Humoral Immune ◽  
Aureus Infection

Staphylococcus aureus (S. aureus) is a leading cause of both healthcare-and community-associated infections globally, which result in severe disease and readily developing antibiotic resistance. Developing an efficacious vaccine against S. aureus is urgently required. In the present study, we selected five conserved antigens, including the secreted factors α-hemolysin (Hla), staphylococcal enterotoxin B (SEB) and the three surface proteins staphylococcal protein A (SpA), iron surface determinant B N2 domain (IsdB-N2) and manganese transport protein C (MntC). They were all well-characterized virulence factor of S. aureus and developed a recombinant five-antigen S. aureus vaccine (rFSAV), rFSAV provided consistent protection in S. aureus lethal sepsis and pneumonia mouse models, and it showed broad immune protection when challenged with a panel of epidemiologically relevant S. aureus strains. Meanwhile, rFSAV immunized mice were able to induce comprehensive cellular and humoral immune responses to reduce bacterial loads, inflammatory cytokine expression, inflammatory cell infiltration and decrease pathology after challenge with a sub-lethal dose of S. aureus. Moreover, the importance of specific antibodies in protection was demonstrated by antibody function tests in vitro and in vivo. Altogether, our data demonstrate that rFSAV is a potentially promising vaccine candidate for defensing against S. aureus infection.

scholarly journals Eriodictyol as a Potential Candidate Inhibitor of Sortase A Protects Mice From Methicillin-Resistant Staphylococcus aureus-Induced Pneumonia

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Wang ◽  
Qianxue Li ◽  
Jiaxin Li ◽  
Shisong Jing ◽  
Yajing Jin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Protein A ◽  
A549 Cells ◽  
Surface Proteins ◽  
Reversible Inhibitor ◽  
Sortase A ◽  
Staphylococcal Protein A ◽  
Potential Candidate ◽  
Methicillin Resistant

New anti-infective approaches are urgently needed to control multidrug-resistant (MDR) pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA). Sortase A (SrtA) is a membrane-bound cysteine transpeptidase that plays an essential role in the catalysis of covalent anchoring of surface proteins to the cell wall of Staphylococcus aureus (S. aureus). The present study reports identification of a flavonoid, eriodictyol, as a reversible inhibitor of SrtA with an IC50 of 2.229 ± 0.014 μg/mL that can be used as an innovative means to counter both resistance and virulence. The data indicated that eriodictyol inhibited the adhesion of the bacteria to fibrinogen and reduced the formation of biofilms and anchoring of staphylococcal protein A (SpA) on the cell wall. The results of fluorescence quenching experiments demonstrated a strong interaction between eriodictyol and SrtA. Subsequent mechanistic studies revealed that eriodictyol binds to SrtA by interacting with R197 amino acid residue. Importantly, eriodictyol reduced the adhesion-dependent invasion of A549 cells by S. aureus and showed a good therapeutic effect in a model of mouse pneumonia induced by S. aureus. Overall, the results indicated that eriodictyol can attenuate MRSA virulence and prevent the development of resistance by inhibiting SrtA, suggesting that eriodictyol may be a promising lead compound for the control of MRSA infections.

scholarly journals The YSIRK-G/S Motif of Staphylococcal Protein A and Its Role in Efficiency of Signal Peptide Processing

2003 ◽  
Vol 185 (9) ◽  
pp. 2910-2919 ◽  
Author(s):  
Taeok Bae ◽  
Olaf Schneewind
Keyword(s):  
Cell Wall ◽  
Signal Peptide ◽  
Protein A ◽  
Surface Proteins ◽  
Signal Peptides ◽  
Staphylococcal Protein A ◽  
Gram Positive ◽  
Peptide Processing ◽  
Staphylococcal Protein ◽  
Sorting Signal

ABSTRACT Many surface proteins of pathogenic gram-positive bacteria are linked to the cell wall envelope by a mechanism requiring a C-terminal sorting signal with an LPXTG motif. Surface proteins of Streptococcus pneumoniae harbor another motif, YSIRK-G/S, which is positioned within signal peptides. The signal peptides of some, but not all, of the 20 surface proteins of Staphylococcus aureus carry a YSIRK-G/S motif, whereas those of surface proteins of Listeria monocytogenes and Bacillus anthracis do not. To determine whether the YSIRK-G/S motif is required for the secretion or cell wall anchoring of surface proteins, we analyzed variants of staphylococcal protein A, an immunoglobulin binding protein with an LPXTG sorting signal. Deletion of the YSIR sequence or replacement of G or S significantly reduced the rate of signal peptide processing of protein A precursors. In contrast, cell wall anchoring or the functional display of protein A was not affected. The fusion of cell wall sorting signals to reporter proteins bearing N-terminal signal peptides with or without the YSIRK-G/S motif resulted in hybrid proteins that were anchored in a manner similar to that of wild-type protein A. The requirement of the YSIRK-G/S motif for efficient secretion implies the existence of a specialized mode of substrate recognition by the secretion pathway of gram-positive cocci. It seems, however, that this mechanism is not essential for surface protein anchoring to the cell wall envelope.

Multilocus Sequence Typing and Staphylococcal Protein A Typing Revealed Novel and Diverse Clones of Methicillin-Resistant Staphylococcus aureus in Seafood and the Aquatic Environment

2017 ◽  
Vol 80 (3) ◽  
pp. 476-481 ◽  
Author(s):  
V. Murugadas ◽  
C. Joseph Toms ◽  
Sara A. Reethu ◽  
K. V. Lalitha
Keyword(s):  
Staphylococcus Aureus ◽  
Aquatic Environment ◽  
Multilocus Sequence Typing ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Protein A ◽  
Staphylococcal Protein A ◽  
Spa Typing ◽  
Methicillin Resistant ◽  
Staphylococcal Protein ◽  
Mrsa Strains

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) has been a global health concern since the 1960s, and isolation of this pathogen from food-producing animals has been increasing. However, little information is available on the prevalence of MRSA and its clonal characteristics in seafood and the aquatic environment. In this study, 267 seafood and aquatic environment samples were collected from three districts of Kerala, India. Staphylococcal protein A (spa) typing and multilocus sequence typing (MLST) was performed for 65 MRSA strains isolated from 20 seafood and aquatic environment samples. The MRSA clonal profiles were t657-ST772, t002-ST5, t334-ST5, t311-ST5, t121-ST8, t186-ST88, t127-ST1, and two non-spa assignable strains. Whole spa gene sequence analysis along with MLST confirmed one strain as t711-ST6 and another as a novel MRSA clone identified for the first time in seafood and the aquatic environment with a t15669 spa type and a new MLST profile of ST420-256-236-66-82-411-477. The MRSA strains were clustered into five clonal complexes based on the goeBURST algorithm, indicating high diversity among MRSA strains in seafood and the aquatic environment. The novel clone formed a separate clonal complex with matches to three loci. This study recommends large-scale spa typing and MLST of MRSA isolates from seafood and the aquatic environment to determine the prevalence of new MRSA clones. This monitoring process can be useful for tracing local spread of MRSA isolates into the seafood production chain in a defined geographical area.

scholarly journals The Synergistic Effect of Nicotine and Staphylococcus aureus on Peri-Implant Infections

2021 ◽  
Vol 9 ◽  
Author(s):  
Yao Hu ◽  
Wen Zhou ◽  
Chengguang Zhu ◽  
Yujie Zhou ◽  
Qiang Guo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Synergistic Effects ◽  
Protein A ◽  
Treated Group ◽  
Combination Group ◽  
Staphylococcal Protein A ◽  
Receptor Activator ◽  
And Staphylococcus Aureus

Smoking is considered a key risk factor for implant survival; however, how it interacts with the pathogens in peri-implant infections is not clear. Here, we identified that nicotine, the key component of cigarette smoking, can interact with Staphylococcus aureus and synergistically induce peri-implant infections in a rat osteolysis model. The nicotine–S. aureus combination group increased the gross bone pathology, osteolysis, periosteal reactions, and bone resorption compared to the nicotine or S. aureus single treated group (p < 0.05). Nicotine did not promote the proliferation of S. aureus both in vitro and in vivo, but it can significantly upregulate the expression of staphylococcal protein A (SpA), a key virulence factor of S. aureus. The nicotine–S. aureus combination also synergistically activated the expression of RANKL (receptor activator of nuclear factor-kappa B ligand, p < 0.05) to promote the development of peri-implant infections. The synergistic effects between nicotine and S. aureus infection can be a new target to reduce the peri-implant infections.

scholarly journals Whole-Genome Epidemiology and Characterization of Methicillin-Susceptible Staphylococcus aureus ST398 From Retail Pork and Bulk Tank Milk in Shandong, China

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaonan Zhao ◽  
Ming Hu ◽  
Cui Zhao ◽  
Qing Zhang ◽  
Lulu Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Protein A ◽  
Whole Genome ◽  
Staphylococcal Protein A ◽  
Sequencing Analysis ◽  
Bulk Tank Milk ◽  
Predominant Type ◽  
Bulk Tank ◽  
The One

Staphylococcus aureus (S. aureus) is now regarded as a zoonotic agent. Methicillin-susceptible S. aureus (MSSA) ST398 is a livestock-associated bacterium that is most prevalent in China, but there are currently no data available for Shandong. Therefore, the aim of this study was to investigate the epidemiology and characterization of MSSA ST398 from retail pork and bulk tank milk (BTM) in Shandong. A total of 67 S. aureus isolates were collected from retail pork between November 2017 and June 2018. Among the isolates, high antimicrobial resistance rates were observed for penicillin (97.0%), and 92.5% of the isolates were multi-drug resistant (MDR). Eight sequence types (STs) were identified in the retail pork isolates, and the predominant type was ST15 (n=26), which was followed by ST398 (n=14). Staphylococcal protein A gene (spa) typing identified spa types t034 and t1255 in MSSA ST398 from retail pork. Using whole-genome sequencing analysis, we described the phylogeny of 29 MSSA ST398 isolates that were obtained from retail pork (n=14) and BTM (n=15). The phylogenetic tree showed that the MSSA ST398 isolates from different sources had the same lineage. Among the 29 MSSA ST398 isolates, five resistance genes were detected, and all isolates carried DHA-1. Fifteen toxin genes were detected, and all isolates carried eta, hla, and hlb. In conclusion, this study found that a high risk for MSSA ST398 was present in retail pork and BTM. These findings have major implications for how investigations of MSSA ST398 outbreaks should be conducted in the One-Health context.

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