REGULATION OF LpxO1 and LpxO2 AND ITS INVOLVEMENT IN POLYMYXIN B RESISTANCE IN Serratia marcescens

MARISCOTTI, J.F.; GARCÍA VÉSCOVI, E.

Mar del Plata

Congreso; LI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2015

SAIB

The lipopolysaccharide (LPS) lipid A is recognized by the innate system. The gram-negative bacteria modify the LPS to avoid host immune system and to resist killing by antimicrobial peptide. S. marcescens is an enteric bacterium that can function as an opportunistic pathogen within immunocompromised hosts. This pathogenic bacterium contains two putative lpxO genes homologues (lpxO1 and lpxO2). LpxO is an oxygenase that 2-hydroxylates specific acyl chains in the lipid A. In this work, we analyzed the regulation of lpxO1 and lpxO2 and its role in antimicrobial peptide resistance. We constructed lpxO1 and lpxO2 mutants in S. marcescens and determined their resistance to polymyxin B. The results show that LpxO1 is necessary for polymyxin B resistance, while LpxO2 is dispensable. In addition, lpxO1 mutant exhibited less swarming motility, suggesting that LpxO1 modification plays a role in swarming. In many bacterial species, modifications in the LPS that confer resistance to antimicrobial peptides are regulated by the PhoP/PhoQ system. Furthermore, in Klebsiella pneumoniae RamA, a transcriptional regulator, functions as an alternate regulator of certain lipid A biosynthesis genes. The contribution of PhoP and RamA in the expression level of lpxO1 and lpxO2 was analyzed by RT-PCR. Our results show that, in Serratia, PhoP and RamA are involved in lpxO1 and lpxO2 transcriptional regulation.