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1.
Microbiol Spectr ; 11(6): e0153623, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-37882578

ABSTRACT

IMPORTANCE: New approaches are needed to discover novel antimicrobials, particularly antibiotics that target the Gram-negative outer membrane. By exploiting bacterial sensing and responses to outer membrane (OM) damage, we used a biosensor approach consisting of polymyxin resistance gene transcriptional reporters to screen natural products and a small drug library for biosensor activity that indicates damage to the OM. The diverse antimicrobial compounds that cause induction of the polymyxin resistance genes, which correlates with outer membrane damage, suggest that these LPS and surface modifications also function in short-term repair to sublethal exposure and are required against broad membrane stress conditions.


Subject(s)
Plants, Medicinal , Pseudomonas Infections , Pseudomonas aeruginosa , Anti-Bacterial Agents/pharmacology , Polymyxins
2.
Sci Total Environ ; 872: 162231, 2023 May 10.
Article in English | MEDLINE | ID: mdl-36796695

ABSTRACT

Multivariate modelling techniques are used by a wide variety of investigations in environmental chemistry. It is surprisingly rare for studies to show a detailed understanding of uncertainties created by modelling or how uncertainties in chemical analysis impact model outputs. It is common to use untrained multivariate models for receptor modelling. These models produce a slightly different output each time they are run. The fact that a single model can provide different results is rarely acknowledged. In this manuscript, we attempt to address this by investigating differences that can be generated using four different receptor models (NMF, ALS, PMF & PVA) to perform source apportionment of polychlorinated biphenyls (PCBs) in surface sediments from Portland Harbor. Results showed that models generally had a strong agreement and identified the same main signatures that represented commercial PCB mixtures, however, subtle differences were identified by; different models, same models but with a different number of end members (EM), and the same model with the same number of end members. As well as identifying different Aroclor-like signatures, the relative proportion of these sources also varied. Depending on which method is selected it may have a significant impact on conclusions of a scientific report or litigation case and ultimately, allocation on who is responsible for paying for remediation. Therefore, care must be taken to understand these uncertainties to select a method that produces consistent results with end members that can be chemically explained. We also investigated a novel approach to use our multivariate models to identify inadvertent sources of PCBs. By using a residual plot produced from one of our models (NMF) we were able to suggest the presence of approximately 30 different potentially inadvertently produced PCBs which account for 6.6 % of the total PCBs in Portland Harbor sediments.

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