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Bharathi Sriram - One of the best experts on this subject based on the ideXlab platform.
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Antistaphylococcal activity of bacteriophage derived chimeric protein p128
BMC Microbiology, 2012Co-Authors: Aradhana Vipra, Srividya Narayanamurthy Desai, Panchali Roy, Raghu Patil, Juliet Roshini Mohan Raj, Nagalakshmi Narasimhaswamy, Vivek Daniel Paul, Ravisha Chikkamadaiah, Bharathi SriramAbstract:Background Bacterial drug resistance is one of the most significant challenges to human health today. In particular, effective antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) are urgently needed. A causal relationship between nasal commensal S. aureus and infection has been reported. Accordingly, elimination of nasal S. aureus reduces the risk of infection. Enzymes that degrade bacterial cell walls show promise as antibacterial agents. Bacteriophage-encoded bacterial cell wall-degrading enzymes exhibit intrinsic bactericidal activity. P128 is a chimeric protein that combines the lethal activity of the phage tail-associated muralytic enzyme of Phage K and the staphylococcal cell wall targeting-domain (SH3b) of lysostaphin. Here we report results of in vitro studies evaluating the susceptibility of staphylococcal strains to this novel protein.
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A novel bacteriophage Tail-Associated Muralytic Enzyme (TAME) from Phage K and its development into a potent Antistaphylococcal protein
BMC Microbiology, 2011Co-Authors: Vivek Daniel Paul, Ravisha Chikkamadaiah, Bharathi Sriram, Sanjeev Saravanan Rajagopalan, Sudarson Sundarrajan, Shilpa E George, Jiya Y Asrani, Renjith Pillai, Murali Durgaiah, Sriram PadmanabhanAbstract:Background Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. However, the rapid emergence of antibiotic resistance limits the choice of therapeutic options for treating infections caused by this organism. Muralytic enzymes from bacteriophages have recently gained attention for their potential as antibacterial agents against antibiotic-resistant gram-positive organisms. Phage K is a polyvalent virulent phage of the Myoviridae family that is active against many Staphylococcus species. Results We identified a phage K gene, designated orf 56, as encoding the phage tail-associated muralytic enzyme (TAME). The gene product (ORF56) contains a C-terminal domain corresponding to cysteine, histidine-dependent amidohydrolase/peptidase (CHAP), which demonstrated muralytic activity on a staphylococcal cell wall substrate and was lethal to S. aureus cells. We constructed N-terminal truncated forms of ORF56 and arrived at a 16-kDa protein (Lys16) that retained Antistaphylococcal activity. We then generated a chimeric gene construct encoding Lys16 and a staphylococcal cell wall-binding SH3b domain. This chimeric protein (P128) showed potent Antistaphylococcal activity on global clinical isolates of S. aureus including methicillin-resistant strains. In addition, P128 was effective in decolonizing rat nares of S. aureus USA300 in an experimental model. Conclusions We identified a phage K gene that encodes a protein associated with the phage tail structure. The muralytic activity of the phage K TAME was localized to the C-terminal CHAP domain. This potent Antistaphylococcal TAME was combined with an efficient Staphylococcus -specific cell-wall targeting domain SH3b, resulting in the chimeric protein P128. This protein shows bactericidal activity against globally prevalent antibiotic resistant clinical isolates of S. aureus and against the genus Staphylococcus in general. In vivo , P128 was efficacious against methicillin-resistant S. aureus in a rat nasal colonization model.
Alan R Smyth - One of the best experts on this subject based on the ideXlab platform.
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early respiratory bacterial detection and Antistaphylococcal antibiotic prophylaxis in young children with cystic fibrosis
Annals of the American Thoracic Society, 2018Co-Authors: Matthew N Hurley, Andrew W Fogarty, Tricia M Mckeever, Christopher H Goss, Margaret Rosenfeld, Alan R SmythAbstract:Rationale: Consensus is lacking regarding Antistaphylococcal antibiotic prophylaxis use for young children with cystic fibrosis. Prophylaxis is recommended in the United Kingdom, but it is recommended against in the United States.Objectives: To test the hypothesis that Antistaphylococcal antibiotic prophylaxis is associated with a decreased risk of Staphylococcus aureus acquisition but no increased risk of Pseudomonas aeruginosa acquisition.Methods: We undertook a longitudinal observational study of children with cystic fibrosis who were recruited from birth (or from their first registry entry in the period) and followed until the age of 4 years (1,500 d) using 2000–2009 data from the UK Cystic Fibrosis Trust and Cystic Fibrosis Foundation registries. Children were excluded if they had a positive culture result for S. aureus or P. aeruginosa, or if they were receiving inhaled antibiotics, at the first encounter. Time to first S. aureus and P. aeruginosa detection in the UK/U.S. cohorts was compared using ...
Vivek Daniel Paul - One of the best experts on this subject based on the ideXlab platform.
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Antistaphylococcal activity of bacteriophage derived chimeric protein p128
BMC Microbiology, 2012Co-Authors: Aradhana Vipra, Srividya Narayanamurthy Desai, Panchali Roy, Raghu Patil, Juliet Roshini Mohan Raj, Nagalakshmi Narasimhaswamy, Vivek Daniel Paul, Ravisha Chikkamadaiah, Bharathi SriramAbstract:Background Bacterial drug resistance is one of the most significant challenges to human health today. In particular, effective antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) are urgently needed. A causal relationship between nasal commensal S. aureus and infection has been reported. Accordingly, elimination of nasal S. aureus reduces the risk of infection. Enzymes that degrade bacterial cell walls show promise as antibacterial agents. Bacteriophage-encoded bacterial cell wall-degrading enzymes exhibit intrinsic bactericidal activity. P128 is a chimeric protein that combines the lethal activity of the phage tail-associated muralytic enzyme of Phage K and the staphylococcal cell wall targeting-domain (SH3b) of lysostaphin. Here we report results of in vitro studies evaluating the susceptibility of staphylococcal strains to this novel protein.
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A novel bacteriophage Tail-Associated Muralytic Enzyme (TAME) from Phage K and its development into a potent Antistaphylococcal protein
BMC Microbiology, 2011Co-Authors: Vivek Daniel Paul, Ravisha Chikkamadaiah, Bharathi Sriram, Sanjeev Saravanan Rajagopalan, Sudarson Sundarrajan, Shilpa E George, Jiya Y Asrani, Renjith Pillai, Murali Durgaiah, Sriram PadmanabhanAbstract:Background Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. However, the rapid emergence of antibiotic resistance limits the choice of therapeutic options for treating infections caused by this organism. Muralytic enzymes from bacteriophages have recently gained attention for their potential as antibacterial agents against antibiotic-resistant gram-positive organisms. Phage K is a polyvalent virulent phage of the Myoviridae family that is active against many Staphylococcus species. Results We identified a phage K gene, designated orf 56, as encoding the phage tail-associated muralytic enzyme (TAME). The gene product (ORF56) contains a C-terminal domain corresponding to cysteine, histidine-dependent amidohydrolase/peptidase (CHAP), which demonstrated muralytic activity on a staphylococcal cell wall substrate and was lethal to S. aureus cells. We constructed N-terminal truncated forms of ORF56 and arrived at a 16-kDa protein (Lys16) that retained Antistaphylococcal activity. We then generated a chimeric gene construct encoding Lys16 and a staphylococcal cell wall-binding SH3b domain. This chimeric protein (P128) showed potent Antistaphylococcal activity on global clinical isolates of S. aureus including methicillin-resistant strains. In addition, P128 was effective in decolonizing rat nares of S. aureus USA300 in an experimental model. Conclusions We identified a phage K gene that encodes a protein associated with the phage tail structure. The muralytic activity of the phage K TAME was localized to the C-terminal CHAP domain. This potent Antistaphylococcal TAME was combined with an efficient Staphylococcus -specific cell-wall targeting domain SH3b, resulting in the chimeric protein P128. This protein shows bactericidal activity against globally prevalent antibiotic resistant clinical isolates of S. aureus and against the genus Staphylococcus in general. In vivo , P128 was efficacious against methicillin-resistant S. aureus in a rat nasal colonization model.
Ravisha Chikkamadaiah - One of the best experts on this subject based on the ideXlab platform.
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Antistaphylococcal activity of bacteriophage derived chimeric protein p128
BMC Microbiology, 2012Co-Authors: Aradhana Vipra, Srividya Narayanamurthy Desai, Panchali Roy, Raghu Patil, Juliet Roshini Mohan Raj, Nagalakshmi Narasimhaswamy, Vivek Daniel Paul, Ravisha Chikkamadaiah, Bharathi SriramAbstract:Background Bacterial drug resistance is one of the most significant challenges to human health today. In particular, effective antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) are urgently needed. A causal relationship between nasal commensal S. aureus and infection has been reported. Accordingly, elimination of nasal S. aureus reduces the risk of infection. Enzymes that degrade bacterial cell walls show promise as antibacterial agents. Bacteriophage-encoded bacterial cell wall-degrading enzymes exhibit intrinsic bactericidal activity. P128 is a chimeric protein that combines the lethal activity of the phage tail-associated muralytic enzyme of Phage K and the staphylococcal cell wall targeting-domain (SH3b) of lysostaphin. Here we report results of in vitro studies evaluating the susceptibility of staphylococcal strains to this novel protein.
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A novel bacteriophage Tail-Associated Muralytic Enzyme (TAME) from Phage K and its development into a potent Antistaphylococcal protein
BMC Microbiology, 2011Co-Authors: Vivek Daniel Paul, Ravisha Chikkamadaiah, Bharathi Sriram, Sanjeev Saravanan Rajagopalan, Sudarson Sundarrajan, Shilpa E George, Jiya Y Asrani, Renjith Pillai, Murali Durgaiah, Sriram PadmanabhanAbstract:Background Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. However, the rapid emergence of antibiotic resistance limits the choice of therapeutic options for treating infections caused by this organism. Muralytic enzymes from bacteriophages have recently gained attention for their potential as antibacterial agents against antibiotic-resistant gram-positive organisms. Phage K is a polyvalent virulent phage of the Myoviridae family that is active against many Staphylococcus species. Results We identified a phage K gene, designated orf 56, as encoding the phage tail-associated muralytic enzyme (TAME). The gene product (ORF56) contains a C-terminal domain corresponding to cysteine, histidine-dependent amidohydrolase/peptidase (CHAP), which demonstrated muralytic activity on a staphylococcal cell wall substrate and was lethal to S. aureus cells. We constructed N-terminal truncated forms of ORF56 and arrived at a 16-kDa protein (Lys16) that retained Antistaphylococcal activity. We then generated a chimeric gene construct encoding Lys16 and a staphylococcal cell wall-binding SH3b domain. This chimeric protein (P128) showed potent Antistaphylococcal activity on global clinical isolates of S. aureus including methicillin-resistant strains. In addition, P128 was effective in decolonizing rat nares of S. aureus USA300 in an experimental model. Conclusions We identified a phage K gene that encodes a protein associated with the phage tail structure. The muralytic activity of the phage K TAME was localized to the C-terminal CHAP domain. This potent Antistaphylococcal TAME was combined with an efficient Staphylococcus -specific cell-wall targeting domain SH3b, resulting in the chimeric protein P128. This protein shows bactericidal activity against globally prevalent antibiotic resistant clinical isolates of S. aureus and against the genus Staphylococcus in general. In vivo , P128 was efficacious against methicillin-resistant S. aureus in a rat nasal colonization model.
Arnold S Bayer - One of the best experts on this subject based on the ideXlab platform.
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use of Antistaphylococcal β lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin resistant staphylococcus aureus role of enhanced daptomycin binding
Clinical Infectious Diseases, 2011Co-Authors: Abhay Dhand, Joe Pogliano, Victor Nizet, Arnold S Bayer, Soojin Yang, Michael Bolaris, Guiquing Wang, George SakoulasAbstract:We used daptomycin plus Antistaphylococcal β-lactams (ASBL) to clear refractory MRSA bacteremia. In vitro studies showed enhanced daptomycin bactericidal activity, increased membrane daptomycin binding, and decrease in positive surface charge induced by ASBLs against daptomycin nonsusceptible MRSA. Addition of ASBLs to daptomycin may be of benefit in refractory MRSA bacteremia. (Although the official designation is “daptomycin nonsusceptiblity,” we will use the term “daptomycin-resistance” in this paper for facility of presentation.)
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diversity in Antistaphylococcal mechanisms among membrane targeting antimicrobial peptides
Infection and Immunity, 2001Co-Authors: S P Koo, Arnold S Bayer, Michael R YeamanAbstract:Many antimicrobial peptides permeabilize the bacterial cytoplasmic membrane. However, it is unclear how membrane permeabilization and antimicrobial activity are related for distinct peptides. This study investigated the relationship between Staphylococcus aureus membrane permeabilization and cell death due to the following Antistaphylococcal peptides: thrombin-induced platelet microbicidal protein 1 (tPMP-1), gramicidin D, and protamine. Isogenic S. aureus strains ISP479C and ISP479R (tPMP-1 susceptible and resistant, respectively), were loaded with the fluorochrome calcein and exposed to a range of concentrations of each peptide. Flow cytometry was then used to monitor membrane permeabilization by quantifying the release of preloaded calcein. Killing was determined by quantitative culture at time points simultaneous to measurement of membrane permeabilization. Membrane permeabilization and killing caused by tPMP-1 occurred in a time- and concentration-dependent manner, reflecting the intrinsic tPMP-1 susceptibilities of ISP479C and ISP479R. In comparison, gramicidin D killed both S. aureus strains to equivalent extents in a concentration-dependent manner between 0.5 to 50 μg/ml, but cell permeabilization only occurred at the higher peptide concentrations (25 and 50 μg/ml). Protamine permeabilized, but did not kill, either strain at concentrations up to 10 mg/ml. Regression analyses revealed different relationships between membrane permeabilization and staphylocidal activity for the distinct antimicrobial peptides. Taken together, these findings demonstrate that permeabilization, per se, does not invariably result in staphylococcal death due to distinct antimicrobial peptides. Thus, although each of these peptides interacts with the S. aureus cytoplasmic membrane, diversity exists in their mechanisms of action with respect to the relationship between membrane permeabilization and staphylocidal activity.