Displaying all 7 publications

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  1. Popat R, Pollitt EJ, Harrison F, Naghra H, Hong KW, Chan KG, et al.
    Evolution, 2015 Sep;69(9):2371-83.
    PMID: 26282874 DOI: 10.1111/evo.12751
    Animals use signals to coordinate a wide range of behaviors, from feeding offspring to predator avoidance. This poses an evolutionary problem, because individuals could potentially signal dishonestly to coerce others into behaving in ways that benefit the signaler. Theory suggests that honest signaling is favored when individuals share a common interest and signals carry reliable information. Here, we exploit the opportunities offered by bacterial signaling to test these predictions with an experimental evolution approach. We show that: (1) reduced relatedness leads to the relative breakdown of signaling, (2) signaling breaks down by the invasion of mutants that show both reduced signaling and reduced response to signal, (3) the genetic route to signaling breakdown is variable, and (4) the addition of artificial signal, to interfere with signal information, also leads to reduced signaling. Our results provide clear support for signaling theory, but we did not find evidence for previously predicted coercion at intermediate relatedness, suggesting that mechanistic details can alter the qualitative nature of specific predictions. Furthermore, populations evolved under low relatedness caused less mortality to insect hosts, showing how signal evolution in bacterial pathogens can drive the evolution of virulence in the opposite direction to that often predicted by theory.
    Matched MeSH terms: Pseudomonas aeruginosa/pathogenicity
  2. Wong TW, Ramli NA
    Carbohydr Polym, 2014 Nov 4;112:367-75.
    PMID: 25129756 DOI: 10.1016/j.carbpol.2014.06.002
    Infection control and wound healing profiles of sodium carboxymethylcellulose (SCMC) films were investigated as a function of their anti-bacterial action, physical structures, polymer molecular weights and carboxymethyl substitution degrees. The films were prepared with in vitro polymer/film and in vivo microbe-colonized wound healing/systemic infection profiles examined. Adhesive high carboxymethyl substituted SCMC films aided healing via attaching to microbes and removing them from wound. Pseudomonas aeruginosa was removed via encapsulating in gelling low molecular weight SCMC film, whereas Staphylococcus aureus was trapped in tight folds of high molecular weight SCMC film. Incomplete microbe removal from wound did not necessary translate to inability to heal as microbe remnant at wound induced fibroblast migration and aided tissue reconstruction. Using no film nonetheless will cause systemic blood infection. SCMC films negate infection and promote wound healing via specific polymer-microbe adhesion, and removal of S. aureus and P. aeruginosa requires films of different polymer characteristics.
    Matched MeSH terms: Pseudomonas aeruginosa/pathogenicity
  3. Sivasothy Y, Krishnan T, Chan KG, Abdul Wahab SM, Othman MA, Litaudon M, et al.
    Molecules, 2016 Mar 21;21(3):391.
    PMID: 27102164 DOI: 10.3390/molecules21030391
    Malabaricones A-C (1-3) and giganteone A (4) were isolated from the bark of Myristica cinnamomea King. Their structures were elucidated and characterized by means of NMR and MS spectral analyses. These isolates were evaluated for their anti-quorum sensing activity using quorum sensing biosensors, namely Escherichia coli [pSB401] and Escherichia coli [pSB1075], whereby the potential of giganteone A (4) as a suitable anti-quorum sensing agent was demonstrated.
    Matched MeSH terms: Pseudomonas aeruginosa/pathogenicity
  4. Dharmalingam K, Tan BK, Mahmud MZ, Sedek SA, Majid MI, Kuah MK, et al.
    J Ethnopharmacol, 2012 Jan 31;139(2):657-63.
    PMID: 22193176 DOI: 10.1016/j.jep.2011.12.016
    Swietenia macrophylla or commonly known as big leaf mahogany, has been traditionally used as an antibacterial and antifungal agent.
    Matched MeSH terms: Pseudomonas aeruginosa/pathogenicity
  5. Abdul-Aziz MH, Abd Rahman AN, Mat-Nor MB, Sulaiman H, Wallis SC, Lipman J, et al.
    Antimicrob Agents Chemother, 2016 01;60(1):206-14.
    PMID: 26482304 DOI: 10.1128/AAC.01543-15
    Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.
    Matched MeSH terms: Pseudomonas aeruginosa/pathogenicity
  6. Asghar A, Tan YC, Zahoor M, Zainal Abidin SA, Yow YY, Khan E, et al.
    Sci Rep, 2021 Jul 05;11(1):13859.
    PMID: 34226594 DOI: 10.1038/s41598-021-92622-0
    The emergence and spread of antimicrobial resistance have been of serious concern to human health and the management of bacterial infectious diseases. Effective treatment of these diseases requires the development of novel therapeutics, preferably free of side effects. In this regard, natural products are frequently conceived to be potential alternative sources for novel antibacterial compounds. Herein, we have evaluated the antibacterial activity of the epicarp extracts of the Malaysian cultivar of yellow rambutan fruit (Nephelium lappaceum L.) against six pathogens namely, Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella enterica. Among a series of solvent extracts, fractions of ethyl acetate and acetone have revealed significant activity towards all tested strains. Chemical profiling of these fractions, via HPLC, LC-MS and GC-MS, has generated a library of potentially bioactive compounds. Downstream virtual screening, pharmacological prediction, and receptor-ligand molecular dynamics simulation have eventually unveiled novel potential antibacterial compounds, which can be extracted for medicinal use. We report compounds like catechin, eplerenone and oritin-4-beta-ol to be computationally inhibiting the ATP-binding domain of the chaperone, DnaK of P. aeruginosa and MRSA. Thus, our work follows the objective to propose new antimicrobials capable of perforating the barrier of resistance posed by both the gram positives and the negatives.
    Matched MeSH terms: Pseudomonas aeruginosa/pathogenicity
  7. Mustafa M, Chan WM, Lee C, Harijanto E, Loo CM, Van Kinh N, et al.
    Int J Antimicrob Agents, 2014 Apr;43(4):353-60.
    PMID: 24636429 DOI: 10.1016/j.ijantimicag.2014.01.017
    Doripenem is approved in the Asia-Pacific (APAC) region for treating nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP), complicated intra-abdominal infections (cIAIs) and complicated urinary tract infections (cUTIs). Clinical usage of doripenem (500mg intravenously, infused over 1h or 4h every 8h for 5-14 days) in APAC was evaluated in a prospective, open-label, non-comparative, multicentre study of inpatients (≥18 years) with NP, VAP, cIAI or cUTI. A total of 216 [intention-to-treat (ITT)] patients received doripenem: 53 NP (24.5%); 77 VAP (35.6%); 67 cIAI (31.0%); and 19 cUTI (8.8%). Doripenem MIC90 values for Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae were 32, 32, 0.094 and 0.64μg/mL, respectively. Doripenem was used most commonly as monotherapy (86.6%) and as second-line therapy (62.0%). The clinical cure rate in clinically evaluable patients was 86.7% at the end of therapy (EOT) and 87.1% at test of cure (TOC) (7-14 days after EOT). In the ITT population, overall clinical cure rates were 66.2% at EOT and 56.5% at TOC. The median duration of hospital stay, intensive care unit (ICU) stay and mechanical ventilation was 20, 12 and 10 days, respectively. Of 146 discharged patients, 7 were re-admitted within 28 days of EOT; 1 VAP patient was re-admitted to the ICU. The all-cause mortality rate was 22.7% (49/216). The most common treatment-related adverse events were diarrhoea (1.4%) and vomiting (1.4%). Doripenem is a viable option for treating APAC patients with NP, VAP, cIAI or cUTI. [ClinicalTrials.gov: NCT 00986102].
    Matched MeSH terms: Pseudomonas aeruginosa/pathogenicity
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