Bacterial Communications in Implant Infections: A Target for an Intelligence War

The status of population density is communicated among bacteria by specific secreted molecules, called pheromones or autoinducers, and the control mechanism is called “quorum-sensing”. Quorum-sensing systems regulate the expression of a panel of genes, allowing bacteria to adapt to modified environmental conditions at a high density of population. The two known different quorum systems are described as the LuxR-LuxI system in gram-negative bacteria, which uses an N-acyl-homoserine lactone (AHL) as signal, and the agr system in gram-positive bacteria, which uses a peptide-tiolactone as signal and the RNAIII as effector molecules. Both in gram-negative and in gram-positive bacteria, quorum-sensing systems regulate the expression of adhesion mechanisms (biofilm and adhesins) and virulence factors (toxins and exoenzymes) depending on population cell density. In gram-negative Pseudomonas aeruginosa, analogs of signaling molecules such as furanone analogs, are effective in attenuating bacterial virulence and controlling bacterial infections. In gram-positive Staphylococcus aureus, the quorum-sensing RNAIII-inhibiting peptide (RIP), tested in vitro and in animal infection models, has been proved to inhibit virulence and prevent infections. Attenuation of bacterial virulence by quorum-sensing inhibitors, rather than by bactericidal or bacteriostatic drugs, is a highly attractive concept because these antibacterial agents are less likely to induce the development of bacterial resistance.

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Antibacterial Activity of Colloidal Silver against Gram-Negative and Gram-Positive Bacteria

Antibiotics ◽

10.3390/antibiotics9010036 ◽

2020 ◽

Vol 9 (1) ◽

pp. 36 ◽

Cited By ~ 4

Author(s):

Andrea Vila Domínguez ◽

Rafael Ayerbe Algaba ◽

Andrea Miró Canturri ◽

Ángel Rodríguez Villodres ◽

Younes Smani

Keyword(s):

Bacterial Infections ◽

Antimicrobial Properties ◽

Multidrug Resistant ◽

Colloidal Silver ◽

Ros Production ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Kill Curve

Due to the emergence of antimicrobial resistance, new alternative therapies are needed. Silver was used to treat bacterial infections since antiquity due to its known antimicrobial properties. Here, we aimed to evaluate the in vitro activity of colloidal silver (CS) against multidrug-resistant (MDR) Gram-negative and Gram-positive bacteria. A total of 270 strains (Acinetobacter baumannii (n = 45), Pseudomonas aeruginosa (n = 25), Escherichia coli (n = 79), Klebsiella pneumoniae (n = 58)], Staphylococcus aureus (n = 34), Staphylococcus epidermidis (n = 14), and Enterococcus species (n = 15)) were used. The minimal inhibitory concentration (MIC) of CS was determined for all strains by using microdilution assay, and time–kill curve assays of representative reference and MDR strains of these bacteria were performed. Membrane permeation and bacterial reactive oxygen species (ROS) production were determined in presence of CS. CS MIC90 was 4–8 mg/L for all strains. CS was bactericidal, during 24 h, at 1× and 2× MIC against Gram-negative bacteria, and at 2× MIC against Gram-positive bacteria, and it did not affect their membrane permeabilization. Furthermore, we found that CS significantly increased the ROS production in Gram-negative with respect to Gram-positive bacteria at 24 h of incubation. Altogether, these results suggest that CS could be an effective treatment for infections caused by MDR Gram-negative and Gram-positive bacteria.

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Effective Small Molecule Antibacterials from a Novel Anti-Protein Secretion Screen

Microorganisms ◽

10.3390/microorganisms9030592 ◽

2021 ◽

Vol 9 (3) ◽

pp. 592

Author(s):

Mohamed Belal Hamed ◽

Ewa Burchacka ◽

Liselotte Angus ◽

Arnaud Marchand ◽

Jozefien De Geyter ◽

...

Keyword(s):

Protein Secretion ◽

Small Molecule ◽

Bacterial Resistance ◽

Bacterial Species ◽

Attractive Potential ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Gram Positive Bacteria

The increasing problem of bacterial resistance to antibiotics underscores the urgent need for new antibacterials. Protein export pathways are attractive potential targets. The Sec pathway is essential for bacterial viability and includes components that are absent from eukaryotes. Here, we used a new high-throughput in vivo screen based on the secretion and activity of alkaline phosphatase (PhoA), a Sec-dependent secreted enzyme that becomes active in the periplasm. The assay was optimized for a luminescence-based substrate and was used to screen a ~240K small molecule compound library. After hit confirmation and analoging, 14 HTS secretion inhibitors (HSI), belonging to eight structural classes, were identified with IC50 < 60 µM. The inhibitors were evaluated as antibacterials against 19 Gram-negative and Gram-positive bacterial species (including those from the WHO’s top pathogens list). Seven of them—HSI#6, 9; HSI#1, 5, 10; and HSI#12, 14—representing three structural families, were bacteriocidal. HSI#6 was the most potent hit against 13 species of both Gram-negative and Gram-positive bacteria with IC50 of 0.4 to 8.7 μM. HSI#1, 5, 9 and 10 inhibited the viability of Gram-positive bacteria with IC50 ~6.9–77.8 μM. HSI#9, 12, and 14 inhibited the viability of E. coli strains with IC50 < 65 μM. Moreover, HSI#1, 5 and 10 inhibited the viability of an E. coli strain missing TolC to improve permeability with IC50 4 to 14 μM, indicating their inability to penetrate the outer membrane. The antimicrobial activity was not related to the inhibition of the SecA component of the translocase in vitro, and hence, HSI molecules may target new unknown components that directly or indirectly affect protein secretion. The results provided proof of the principle that the new broad HTS approach can yield attractive nanomolar inhibitors that have potential as new starting compounds for optimization to derive potential antibiotics.

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In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01407-05 ◽

2006 ◽

Vol 50 (6) ◽

pp. 2261-2264 ◽

Cited By ~ 36

Author(s):

Hee-Soo Park ◽

Hyun-Joo Kim ◽

Min-Jung Seol ◽

Dong-Rack Choi ◽

Eung-Chil Choi ◽

...

Keyword(s):

Antibacterial Activities ◽

The Other ◽

Vitro Activity ◽

Gram Negative Bacteria ◽

In Vitro Activity ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

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PTS 50: Past, Present and Future, or Diauxie Revisited

Journal of Molecular Microbiology and Biotechnology ◽

10.1159/000369809 ◽

2015 ◽

Vol 25 (2-3) ◽

pp. 79-93 ◽

Cited By ~ 9

Author(s):

Joseph W. Lengeler

Keyword(s):

Catabolite Repression ◽

Biological Significance ◽

Cellular Growth ◽

Gram Positive ◽

Gram Negative ◽

Inducer Exclusion ◽

Gram Positive Bacteria ◽

Cellular Control

Past: The title ‘PTS 50 or The PTS after 50 years' relies on the first description in 1964 of the phosphoenolpyruvate-dependent carbohydrate:phosphotransferase system (PTS) by Kundig, Gosh and Roseman [Proc Natl Acad Sci USA 1964;52:1067-1074]. The system comprised proteins named Enzyme I, HPr and Enzymes II, as part of a novel PTS for carbohydrates in Gram-negative and Gram-positive bacteria, whose ‘biological significance remained unclear'. In contrast, studies which would eventually lead to the discovery of the central role of the PTS in bacterial metabolism had been published since before 1942. They are primarily linked to names like Epps and Gale, J. Monod, Cohn and Horibata, and B. Magasanik, and to phenomena like ‘glucose effects', ‘diauxie', ‘catabolite repression' and carbohydrate transport. Present: The pioneering work from Roseman's group initiated a flood of publications. The extraordinary progress from 1964 to this day in the qualitative and in vitro description of the genes and enzymes of the PTS, and of its multiple roles in global cellular control through ‘inducer exclusion', gene induction and ‘catabolite repression', in cellular growth, in cell differentiation and in chemotaxis, as well as the differences of its functions between Gram-positive and Gram-negative bacteria, was one theme of the meeting and will not be treated in detail here. Future: At the 1988 Paris meeting entitled ‘The PTS after 25 years', Saul Roseman predicted that ‘we must describe these interactions [of the PTS components] in a quantitative way [under] in vivo conditions'. I will present some results obtained by our group during recent years on the old phenomenon of diauxie by means of very fast and quantitative tests, measured in vivo, and obtained from cultures of isogenic mutant strains growing under chemostat conditions. The results begin to hint at the problems relating to future PTS research, but also to the ‘true science' of Roseman.

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Działanie in vitro olejku cyprysowego (Oleum Cupressi) na bakterie beztlenowe

Postępy Fitoterapii ◽

10.25121/pf.2019.20.2.91 ◽

2019 ◽

Vol 20 (2) ◽

Author(s):

Anna Kędzia ◽

Elżbieta Hołderna-Kędzia

Keyword(s):

Anaerobic Bacteria ◽

Growth Control ◽

Cupressus Sempervirens ◽

Tannerella Forsythia ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Gram Positive Cocci ◽

Porphyromonas Levii

Introduction. Cypress (Cupressus sempervirens L.) belongs to the family Cupressaceae. It is evergreen, and grows in Mediterranean region. The Cypress leaves and young branches are utilized to produce the essential oil. Cypress oil contain a number of components, in it α-pinene, Δ3-carene, α-terpinyl acetate, cedrol, α-terpinolene, β-myrcene, limonene, α-terpineolene, terpinen-4-ol, β-pinene, δ-cadinene and sabinene. The oil is used in therapy different diseases. It to have antimicrobial activity. Aim. The aim of the date was evaluation the susceptibility of anaerobic bacteria to Cypress oil. Material and methods. The anaerobic bacteria were isolated from patients. The 62 microorganisms, in it 36 strains of Gram-negative rods, 14 Gram-positive cocci and 12 Gram-positive rods, and 7 reference strains were tested. Susceptibility (MIC) was determined by means of plate dilution technique in Brucella agar supplemented with 5% defibrynated sheep blood, menadione and hemin. The Cypress oil was dissolved in DMSO and distilled water to obtain final following concentrations: 2.5, 5.0, 7.5, 10.0, 15.0 and 20.0 mg/ml. Inoculum containing 106 CFU per 1 ml was seeded with Steers replicator upon the agar with oil or without the oil (strains growth control). The agar plates was incubated in anaerobic condition in anaerobic jar in 37°C for 48 hrs. The MIC was interpreted as the lowest concentration of Cypress oil inhibiting the growth of tested bacteria. Results. The results indicated that from among Gram-negative rods the most susceptible to Cypress oil was the strains from genus Tannerella forsythia (MIC < 2.5-5.0 mg/ml), Bacteroides uniformis (MIC = 5.0 mg/ml), Bacteroides vulgatus and Porphyromonas asaccharolytica (MIC 5.0-7.5 mg/ml) and Porphyromonas levii (MIC = 7.5 mg/ml). The strains from genera Fusobacterium and of Bacteroides fragilis were the susceptible to 2.5-≥ 20.0 mg/ml. The Cypress oil was least active towards Prevotella and Parabacteroides strains (MIC ≥ 20.0 mg/ml).The tested Gram-positive cocci were more susceptible. The growth of the strains were inhibited by concentrations in ranges ≤ 2.5-7.5 mg/ml. The oil was minor active towards Gram-positive rods (MIC ≤ 2.5-20.0 mg/ml). Among the strains the genus of Actinomyces odontolyticus (MIC = 5.0 mg/ml) and Actinomyces viscosus (MIC ≤ 2.5-7.5 mg/ml) were the most susceptible. The growth of rods of Bifidobacterium breve was inhibited by concentrations 10.0 mg/ml. The data indicates that the Gram-negative rods were the less susceptible than Gram-positive bacteria to cypress oil. Conclusions. Among Gram-negative rods the most susceptible were the strains Tannerella forsythia, Bacteroides uniformis, Bacteroides vulgatus, Porphyromonas asaccharolytica and Porphyromonas levii. The oil was more active against Gram-positive cocci. Gram-positive anaerobic bacteria demonstrate the more susceptible to Cypress oil then Gram-positive rods.

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In Vitro Antimicrobial Activities of β-Lactams, Aminoglycosides, Quinolones, Glycopeptides and Trimethoprim-Sulfamethoxazole Against Gram-Negative and Gram-Positive Bacteria Isolated from Patients with Intraabdominal Infections

Advances in Abdominal Surgery 2002 ◽

10.1007/978-94-017-0637-7_1 ◽

2002 ◽

pp. 3-12

Author(s):

Giovanna Branca ◽

Teresa Spanu ◽

Fiammetta Leone ◽

Patrizia Mazzella ◽

Giovanni Fadda

Keyword(s):

Antimicrobial Activities ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Intraabdominal Infections

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TSPphg Lysin from the Extremophilic Thermus Bacteriophage TSP4 as a Potential Antimicrobial Agent against Both Gram-Negative and Gram-Positive Pathogenic Bacteria

Viruses ◽

10.3390/v12020192 ◽

2020 ◽

Vol 12 (2) ◽

pp. 192 ◽

Cited By ~ 6

Author(s):

Feng Wang ◽

Xinyu Ji ◽

Qiupeng Li ◽

Guanling Zhang ◽

Jiani Peng ◽

...

Keyword(s):

Bacterial Infections ◽

Pathogenic Bacteria ◽

Infection Model ◽

Bacterial Cells ◽

Skin Damage ◽

Gram Positive ◽

Antibiotic Resistant ◽

Gram Negative

New strategies against antibiotic-resistant bacterial pathogens are urgently needed but are not within reach. Here, we present in vitro and in vivo antimicrobial activity of TSPphg, a novel phage lysin identified from extremophilic Thermus phage TSP4 by sequencing its whole genome. By breaking down the bacterial cells, TSPphg is able to cause bacteria destruction and has shown bactericidal activity against both Gram-negative and Gram-positive pathogenic bacteria, especially antibiotic-resistant strains of Klebsiella pneumoniae, in which the complete elimination and highest reduction in bacterial counts by greater than 6 logs were observed upon 50 μg/mL TSPphg treatment at 37 °C for 1 h. A murine skin infection model further confirmed the in vivo efficacy of TSPphg in removing a highly dangerous and multidrug-resistant Staphylococcus aureus from skin damage and in accelerating wound closure. Together, our findings may offer a therapeutic alternative to help fight bacterial infections in the current age of mounting antibiotic resistance, and to shed light on bacteriophage-based strategies to develop novel anti-infectives.

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Type I and Type II mechanisms of antimicrobial photodynamic therapy: An in vitro study on gram-negative and gram-positive bacteria

Lasers in Surgery and Medicine ◽

10.1002/lsm.22045 ◽

2012 ◽

Vol 44 (6) ◽

pp. 490-499 ◽

Cited By ~ 168

Author(s):

Liyi Huang ◽

Yi Xuan ◽

Yuichiro Koide ◽

Timur Zhiyentayev ◽

Masamitsu Tanaka ◽

...

Keyword(s):

Photodynamic Therapy ◽

In Vitro Study ◽

Vitro Study ◽

Type I ◽

Antimicrobial Photodynamic Therapy ◽

Type Ii ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

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Immunization with 3-oxododecanoyl-l-homoserine lactone–protein conjugate protects mice from lethal Pseudomonas aeruginosa lung infection

Journal of Medical Microbiology ◽

10.1099/jmm.0.46658-0 ◽

2006 ◽

Vol 55 (10) ◽

pp. 1381-1387 ◽

Cited By ~ 68

Author(s):

Shinichi Miyairi ◽

Kazuhiro Tateda ◽

Etsu T. Fuse ◽

Chihiro Ueda ◽

Hiroaki Saito ◽

...

Keyword(s):

Quorum Sensing ◽

Specific Antibody ◽

Bacterial Infections ◽

Inflammatory Responses ◽

Critical Role ◽

Lung Infection ◽

Homoserine Lactone ◽

Vaccine Strategy ◽

Protein Conjugate

Quorum-sensing systems have been reported to play a critical role in the pathogenesis of several bacterial infections. Recent data have demonstrated that Pseudomonas N-3-oxododecanoyl-l-homoserine lactone (3-oxo-C12-homoserine lactone, 3-oxo-C12-HSL), but not N-butanoyl-l-homoserine lactone (C4-HSL), induces apoptosis in macrophages and neutrophils. In the present study, the effects of active immunization with 3-oxo-C12-HSL–carrier protein conjugate on acute P. aeruginosa lung infection in mice were investigated. Immunization with 3-oxo-C12-HSL–BSA conjugate (subcutaneous, four times, at 2-week intervals) elaborated significant amounts of specific antibody in serum. Control and immunized mice were intranasally challenged with approximately 3×106 c.f.u. P. aeruginosa PAO1, and survival was then compared. All control mice died by day 2 post bacterial challenge, while 36 % of immunized mice survived to day 4 (P<0.05). Interestingly, bacterial numbers in the lungs did not differ between control and immunized groups, whereas the levels of pulmonary tumour necrosis factor (TNF)-α in the immunized mice were significantly lower than those of control mice (P<0.05). Furthermore, the extractable 3-oxo-C12-HSL levels in serum and lung homogenate were also significantly diminished in the immunized mice. Immune serum completely rescued reduction of cell viability by 3-oxo-C12-HSL-mediated apoptosis in macrophages in vitro. These results demonstrated that specific antibody to 3-oxo-C12-HSL plays a protective role in acute P. aeruginosa infection, probably through blocking of host inflammatory responses, without altering lung bacterial burden. The present data identify a promising potential vaccine strategy targeting bacterial quorum-sensing molecules, including autoinducers.

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