Resazomycins Alter the Expression of Outer Membrane Lipoproteins in Francisella tularensis

Janelle Stack*, Autumn Grace Dodson*, and Deanna M. Schmitt
Department of Biological Sciences, West Liberty University, West Liberty, WV 26074

Presentation Category: Biological Sciences (Poster Presentation)

Student’s Major: Human Biology

Multidrug-resistant bacteria pose a significant threat to global public health. The development of new antibiotics is essential to combat this public health crisis. Recently, we identified a novel family of compounds, resazomycins, which exhibit antimicrobial activity against select Gram-negative bacteria including the human pathogen Francisella tularensis (Ft). Most of the Gram-negative bacteria that are sensitive to resazomycins possess a unique lipoprotein sorting complex (LolDF) that differs from other Gram-negative bacteria. Since the antimicrobial activity of resazomycins appears to selectively target bacteria with LolDF, we hypothesized that this sorting machinery is a potential target of these compounds. To test this hypothesis, we measured differences in the expression of the major Ft lipoprotein LpnA in the absence and presence of resazomycins. Treatment with resazomycins resulted in reduced expression of LpnA in the outer membrane of Ft suggesting improper sorting of lipoproteins by LolDF. Furthermore, Ft bacteria treated with resazomycins are more sensitive to select detergents and antibiotics likely due to increased permeability of the outer membrane correlating with reduced lipoprotein expression.

Funding: NIH Grant P20GM103434

Program/mechanism supporting research/creative efforts: a West Virginia SURE program