antibiotic resistance • fluorescence-based assay • metallo-β-lactamase (MBL) • NDM-1 • thiols.ABSTRACT: Resistance to β-lactam antibiotics can be mediated by metallo-β-lactamase enzymes (MBLs). An MBL inhibitor could restore the effectiveness of β-lactams. We report on the evaluation of approved thiol-containing drugs as inhibitors of NDM-1, VIM-1 and IMP-7. Drugs were assessed by a novel assay using a purchasable fluorescent substrate and thermal shift. Best compounds were tested in antimicrobial susceptibility assay. Using these orthogonal screening methods we identified drugs which restored the activity of Imipenem.INTRODUCTION:

CspA of the Lyme disease spirochete

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Background: Recruitment of plasminogen is important for efficient dissemination of Borrelia burgdorferi. Results: BBA70 of B. burgdorferi binds plasminogen, and following activation, bound plasmin can cleave fibrinogen and inactivate the key complement components C3b and C5. Conclusion: BBA70 is a potent plasminogen-binding protein.Significance: Investigation suggests that binding of plasminogen may aid in pathogen dissemination and inhibit bacteriolytic effects of the host complement system.

Acinetobacter baumannii is an emerging opportunistic pathogen, responsible for up to 10% of gram-negative, nosocomial infections. The global increase of multidrug-resistant and pan-resistant Acinetobacter isolates presents clinicians with formidable challenges. To establish a persistent infection,A. baumannii must overcome the detrimental effects of complement as the first line of defense against invading microorganisms. However, the immune evasion principles underlying serum resistance inA. baumannii remain elusive. Here, we identified a novel plasminogen-binding protein, termed CipA. Bound plasminogen, upon conversion to active plasmin, degraded fibrinogen and complement C3b and contributed to serum resistance. Furthermore, CipA directly inhibited the alternative pathway of complement in vitro, irrespective of its ability to bind plasminogen. A CipA-deficient mutant was efficiently killed by human serum and showed a defect in the penetration of endothelial monolayers, demonstrating that CipA is a novel multifunctional protein that contributes to the pathogenesis ofA. baumannii.