scholarly journals Secretory Phospholipase A2 Is the Principal Bactericide for Staphylococci and Other Gram-Positive Bacteria in Human Tears

1998 ◽  
Vol 66 (6) ◽  
pp. 2791-2797 ◽  
Author(s):  
Xiao-Dan Qu ◽  
Robert I. Lehrer

ABSTRACT We examined human tears for molecules that killed gram-positive bacteria. The principal mediator of bactericidal activity against staphylococci proved to be a calcium-dependent enzyme, secretory phospholipase A2. Whereas the concentration of secretory phospholipase A2 in the normal tear film exceeded 30 μg/ml, only 1.1 ng (<0.1 nM) of the enzyme per ml sufficed to killListeria monocytogenes and 15 to 80 ng/ml killedStaphylococcus aureus. Despite its efficacy against gram-positive bacteria, secretory phospholipase A2 lacked bactericidal activity against gram-negative organisms (Escherichia coli, Salmonella typhimurium, andPseudomonas aeruginosa) when tested in the ionic environment of tears. Given the presence of secretory phospholipase A2 in tears, intestinal secretions, and leukocytes, this enzyme may play a substantial role in innate mucosal and systemic bactericidal defenses against gram-positive bacteria.

Author(s):  
Erum Malik ◽  
David A. Phoenix ◽  
Timothy J. Snape ◽  
Frederick Harris ◽  
Jaipaul Singh ◽  
...  

AbstractHere the hypothesis that linearized esculentin 2EM (E2EM-lin) from Glandirana emeljanovi possesses pH dependent activity is investigated. The peptide showed weak activity against Gram-negative bacteria (MLCs ≥ 75.0 μM) but potent efficacy towards Gram-positive bacteria (MLCs ≤ 6.25 μM). E2EM-lin adopted an α-helical structure in the presence of bacterial membranes that increased as pH was increased from 6 to 8 (↑ 15.5–26.9%), whilst similar increases in pH enhanced the ability of the peptide to penetrate (↑ 2.3–5.1 mN m−1) and lyse (↑ 15.1–32.5%) these membranes. Theoretical analysis predicted that this membranolytic mechanism involved a tilted segment, that increased along the α-helical long axis of E2EM-lin (1–23) in the N → C direction, with −  < µH > increasing overall from circa − 0.8 to − 0.3. In combination, these data showed that E2EM-lin killed bacteria via novel mechanisms that were enhanced by alkaline conditions and involved the formation of tilted and membranolytic, α-helical structure. The preference of E2EM-lin for Gram-positive bacteria over Gram-negative organisms was primarily driven by the superior ability of phosphatidylglycerol to induce α-helical structure in the peptide as compared to phosphatidylethanolamine. These data were used to generate a novel pore-forming model for the membranolytic activity of E2EM-lin, which would appear to be the first, major reported instance of pH dependent AMPs with alkaline optima using tilted structure to drive a pore-forming process. It is proposed that E2EM-lin has the potential for development to serve purposes ranging from therapeutic usage, such as chronic wound disinfection, to food preservation by killing food spoilage organisms.


2009 ◽  
Vol 55 (5) ◽  
pp. 627-632 ◽  
Author(s):  
Thomas Candela ◽  
Marie Moya ◽  
Michel Haustant ◽  
Agnès Fouet

Poly-γ-glutamate has been described in many Gram-positive organisms. When anchored to the surface, it is a capsule and as such a virulence factor. Based on sequence similarities, few Gram-negative organisms have been suggested to synthesize poly-γ-glutamate. For the first time, a Gram-negative bacterium, Fusobacterium nucleatum , is shown to produce and secrete poly-γ-glutamate. Putative poly-γ-glutamate-synthesizing genes from Gram-negative organisms have been compared with their Gram-positive homologs by in silico analysis, i.e., gene sequence and phylogenetic analysis. Clusters of three instead of four genes were highlighted by our screen. The products of the first two genes display similarity with their Gram-positive equivalents, yet the sequences from the Gram-negative organisms can be distinguished from those of the Gram-positives. Interestingly, the sequence of the predicted product of the third gene is conserved among Gram-negative bacteria but displays no similarity to that of either the third or fourth gene of the Gram-positive operons. It is suggested that, like for Gram-positive bacteria, poly-γ-glutamate has a role in virulence for pathogens and one in survival for other Gram-negative bacteria.


2004 ◽  
Vol 48 (7) ◽  
pp. 2771-2777 ◽  
Author(s):  
Laurel S. Almer ◽  
Jennifer B. Hoffrage ◽  
Erika L. Keller ◽  
Robert K. Flamm ◽  
Virginia D. Shortridge

ABSTRACT In vitro activities of ABT-492, ciprofloxacin, levofloxacin, trovafloxacin, moxifloxacin, gatifloxacin, and gemifloxacin were compared. ABT-492 was more potent against quinolone-susceptible and -resistant gram-positive organisms, had activity similar to that of ciprofloxacin against certain members of the family Enterobacteriaceae, and had comparable activity against quinolone-susceptible, nonfermentative, gram-negative organisms. Bactericidal activity of ABT-492 was also evaluated.


2017 ◽  
Vol 199 (11) ◽  
Author(s):  
Krista M. Armbruster ◽  
Timothy C. Meredith

ABSTRACT Bacterial lipoproteins are embedded in the cell membrane of both Gram-positive and Gram-negative bacteria, where they serve numerous functions central to cell envelope physiology. Lipoproteins are tethered to the membrane by an N-acyl-S-(mono/di)-acyl-glyceryl-cysteine anchor that is variously acylated depending on the genus. In several low-GC, Gram-positive firmicutes, a monoacyl-glyceryl-cysteine with an N-terminal fatty acid (known as the lyso form) has been reported, though how it is formed is unknown. Here, through an intergenic complementation rescue assay in Escherichia coli, we report the identification of a common orthologous transmembrane protein in both Enterococcus faecalis and Bacillus cereus that is capable of forming lyso-form lipoproteins. When deleted from the native host, lipoproteins remain diacylated with a free N terminus, as maturation to the N-acylated lyso form is abolished. Evidence is presented suggesting that the previously unknown gene product functions through a novel intramolecular transacylation mechanism, transferring a fatty acid from the diacylglycerol moiety to the α-amino group of the lipidated cysteine. As such, the discovered gene has been named lipoprotein intramolecular transacylase (lit), to differentiate it from the gene for the intermolecular N-acyltransferase (lnt) involved in triacyl lipoprotein biosynthesis in Gram-negative organisms. IMPORTANCE This study identifies a new enzyme, conserved among low-GC, Gram-positive bacteria, that is involved in bacterial lipoprotein biosynthesis and synthesizes lyso-form lipoproteins. Its discovery is an essential first step in determining the physiological role of N-terminal lipoprotein acylation in Gram-positive bacteria and how these modifications impact bacterial cell envelope function.


2013 ◽  
Vol 57 (10) ◽  
pp. 4653-4655 ◽  
Author(s):  
P. Cottagnoud ◽  
M. Cottagnoud ◽  
F. Acosta ◽  
A. Stucki

ABSTRACTCeftaroline is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistantStaphylococcus aureus(MRSA) and penicillin-resistantStreptococcus pneumoniae, as well as common Gram-negative organisms. This study tested the prodrug, ceftaroline fosamil, against a penicillin-sensitive and a penicillin-resistant strain ofS. pneumoniaein an experimental rabbit meningitis model. The penetration of ceftaroline into inflamed meninges was approximately 14%. Ceftaroline fosamil was slightly superior to ceftriaxone against the penicillin-sensitive strain and significantly superior to the combination of ceftriaxone and vancomycin against the penicillin-resistant strain.


1995 ◽  
Vol 39 (4) ◽  
pp. 964-970 ◽  
Author(s):  
R K Flamm ◽  
C Vojtko ◽  
D T Chu ◽  
Q Li ◽  
J Beyer ◽  
...  

ABT-719 (A-86719.1) is the first compound of a new class of novel DNA gyrase inhibitors, the 2-pyridones, with potent antibacterial activity against gram-positive, gram-negative, and anaerobic organisms. ABT-719 was more active than ciprofloxacin, sparfloxacin, and clinafloxacin against gram-positive bacteria. ABT-719 was particularly active against Staphylococcus aureus (MIC at which 90% of the isolates were inhibited [MIC90] = 0.015 micrograms/ml) and Streptococcus pneumoniae (MIC90 = 0.03 micrograms/ml). ABT-719 was also the most active of the compounds tested against ciprofloxacin-resistant S. aureus isolates, with an MIC90 of 0.25 micrograms/ml, compared with 64 micrograms/ml for ciprofloxacin. Against gram-negative organisms, ABT-719 was as active as or slightly more active than ciprofloxacin and was the most active compound against ciprofloxacin-resistant Pseudomonas aeruginosa (MIC90 = 2.0 micrograms/ml). ABT-719 was also the most active compound against both gram-positive and gram-negative anaerobes, with MIC90s ranging from 0.12 to 0.25 micrograms/ml.


2000 ◽  
Vol 44 (1) ◽  
pp. 164-166 ◽  
Author(s):  
Richard N. Greenberg ◽  
Michael T. Newman ◽  
Saeed Shariaty ◽  
Richard W. Pectol

ABSTRACT The efficacy and safety of three oral fluoroquinolones (lomefloxacin, levofloxacin, and ciprofloxacin) for the treatment of chronic osteomyelitis were analyzed. Twenty-seven patients had documented infections with quinolone-sensitive organisms and received either lomefloxacin, levofloxacin, or ciprofloxacin. Levofloxacin was effective therapy for 9 of 15 (60%) patients. Lomefloxacin was effective therapy for five of seven (71%) patients, and ciprofloxacin was effective therapy for two of five patients (40%). Average follow-up was 11.8 months for patients who completed the course of therapy, and the average duration of therapy was 60.6 days. Gram-positive bacteria were isolated from 18 patients, and 11 patients were cured. Oral fluoroquinolones can be safe, effective therapy if they are given for a prolonged course as treatment for infections caused by susceptible gram-positive as well as gram-negative organisms and in combination with adequate surgical debridement.


Author(s):  
B.K. Ghosh

Periplasm of bacteria is the space outside the permeability barrier of plasma membrane but enclosed by the cell wall. The contents of this special milieu exterior could be regulated by the plasma membrane from the internal, and by the cell wall from the external environment of the cell. Unlike the gram-negative organism, the presence of this space in gram-positive bacteria is still controversial because it cannot be clearly demonstrated. We have shown the importance of some periplasmic bodies in the secretion of penicillinase from Bacillus licheniformis.In negatively stained specimens prepared by a modified technique (Figs. 1 and 2), periplasmic space (PS) contained two kinds of structures: (i) fibrils (F, 100 Å) running perpendicular to the cell wall from the protoplast and (ii) an array of vesicles of various sizes (V), which seem to have evaginated from the protoplast.


Author(s):  
Jacob S. Hanker ◽  
Paul R. Gross ◽  
Beverly L. Giammara

Blood cultures are positive in approximately only 50 per cent of the patients with nongonococcal bacterial infectious arthritis and about 20 per cent of those with gonococcal arthritis. But the concept that gram-negative bacteria could be involved even in chronic arthritis is well-supported. Gram stains are more definitive in staphylococcal arthritis caused by gram-positive bacteria than in bacterial arthritis due to gram-negative bacteria. In the latter situation where gram-negative bacilli are the problem, Gram stains are helpful for 50% of the patients; they are only helpful for 25% of the patients, however, where gram-negative gonococci are the problem. In arthritis due to gram-positive Staphylococci. Gramstained smears are positive for 75% of the patients.


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