|WRIGHT, LORI - University Of Rochester|
|ISABELLA, VINCENT - University Of Rochester|
|HUNTLEY, JASON - University Of Toledo|
|PAVELKA,JR., MARTIN - University Of Rochester|
Submitted to: Journal of Bacteriology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/9/2015
Publication Date: 3/9/2015
Citation: Lovullo, E.D., Wright, L.F., Isabella, V., Huntley, J., Pavelka,Jr., M.S. 2015. Revisiting the gram-negative lipoprotein paradigm. Journal of Bacteriology. doi: 10.1128/JB.02414-14.
Interpretive Summary: The bacterium Francisella tularensis is the causative agent of tularemia and a potential biological weapon. Scientists at University of Rochester School of Medicine and Dentistry, University of Toledo and USDA Agriculture Research Service, Center for Medical, Agricultural and Veterinary Entomology examined the processing of lipids in the outer membrane of this bacterium. The impact of a deleting a gene producing an enzyme that adds lipids onto the lipoproteins embedded in the outer membrane was assessed. The work suggests that Gram-negative bacteria fall into two groups, one in which full lipoprotein processing is essential, and one in which the final processing step is not essential. This finding will provide guidance on limiting utilization of antimicrobials that block this lipid processing pathways.
Technical Abstract: The processing of lipoproteins (lpps) in Gram-negative bacteria is generally considered to be an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein n-acyltransferase. The mature lipoproteins are then sorted by the Lol system, with most lpps inserted into the outer membrane (OM). We show here that the lnt gene is not essential to the Gram-negative pathogen Francisella tularensis subsp. tularensis strain Schu and the live vaccine strain LVS. An LVS delta-lnt mutant has a small colony phenotype on sucrose medium, and increased susceptibility to globomycin and rifampicin. We provide data showing that the OM lipoprotein Tul4A (LpnA) is diacylated but that it, and its paralog Tul4B (LpnB), still sort to the OM in the delta-lnt mutant. We present a model in which the Lol sorting pathway of Francisella has a modified ABC transporter system that is capable of recognizing and sorting both triacylated and diacylated lipoproteins and show that this modified system is present in many other Gram-negative bacteria. We examined this model using Neisseria gonorrhoeae, which has the same Lol architecture as that of Francisella, and show that the lnt gene is not essential in this organism. This work suggests that Gram-negative bacteria fall into two groups, one in which full lipoprotein processing is essential, and one in which the final acylation step is not essential, potentially due to the ability of the Lol sorting pathway in these bacteria to sort immature apolipoproteins to the OM.