TolC Homologue of Brucella suis Is Involved in Resistance to Antimicrobial Compounds and Virulence

• Published in: Infection and Immunity 2007-01, Vol.75 (1), p.379-389
• Main Authors: Posadas, Diana M, Martín, Fernando A, Sabio y García, Julia V, Spera, Juan M, Delpino, M. Victoria, Baldi, Pablo, Campos, Eleonora, Cravero, Silvio L, Zorreguieta, Angeles
• Format: Article
• Language: English
• Subjects: Animals; Anti-Infective Agents - pharmacology; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - metabolism; Bacteriology; Biological and medical sciences; Brucella suis; Brucella suis - drug effects; Brucella suis - pathogenicity; Cloning, Molecular; Drug Resistance - genetics; Escherichia coli; Female; Fundamental and applied biological sciences. Psychology; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Molecular Pathogenesis; Phylogeny; Polymerase Chain Reaction; Virulence
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01349-06

Brucellaspp., like other pathogens, must cope with the environment of diversehost niches during the infection process. In doing this, pathogensevolved different type of transport systems to help them survive anddisseminate within the host. Members of the TolC family have been shownto be involved in the export of chemically diverse molecules rangingfrom large protein toxins to small toxic compounds. The role ofproteins from the TolC family in Brucella and otherα-2-proteobacteria has been explored little. The gene encodingthe unique member of the TolC family from Brucella suis (BepC)was cloned and expressed in an Escherichia coli mutantdisrupted in the gene encoding TolC, which has the peculiarity of beinginvolved in diverse transport functions. BepC fully complemented theresistance to drugs such as chloramphenicol and acriflavine but wasincapable of restoring hemolysin secretion in the tolC mutantof E. coli. An insertional mutation in the bepC genestrongly affected the resistance phenotype of B. suis to bilesalts and toxic chemicals such as ethidium bromide and rhodamine andsignificantly decreased the resistance to antibiotics such aserythromycin, ampicillin, tetracycline, and norfloxacin. Moreover, theB. suis bepC mutant was attenuated in the mouse model ofinfection. Taken together, these results suggest that BepC-dependentefflux processes of toxic compounds contribute to B. suissurvival inside thehost.