Identification of a Brucella outer membrane protein central for the adaptation to environmental changes

EZEQUIEL VALGUARNERA; JUAN M. SPERA; JUAN E. UGALDE

Chicago

Conferencia; 66th Brucellosis Research Conference; 2013

All organisms, including bacteria, face constant environmental changes and must adapt to them in order to survive. To achieve this, they have to be capable of decoding the extremely diverse extracellular cues and alter their physiology depending on precise needs. In particular, many pathogens that alternate between free living conditions and their hosts, encounter completely different environments which vary in temperature, nutrient availability, oxygen tension and presence or absence of an immune system among other stimuli. In order to adapt to each of these scenarios, pathogenic bacteria must be able to sense the cues present in each of them and modify their biology appropriately. Here, we present the identification in Brucella of a gene (cgpA) which is conserved in all alpha-proteobacteria that codes for a small protein (84 amino acids) with an outer membrane localization and is involved in the adaptation of the bacteria to diverse environmental conditions. A null mutant in cgpA is unable to replicate at low temperatures (23°C) in solid media and, in liquid media, is incapable of transitioning from the lag to the log phase, although at 37°C the strain grows as the wild type parental one in both conditions, indicating that the mutant is unable to sense and respond to the temperature shift. Lipid composition analysis of total membranes of both strains at 37°C and 23°C indicated that the mutant is also unable to modify its membrane content in response to temperature. Moreover, the mutant strain is severely attenuated in macrophages but actually overreplicates in mice during the acute phase of the infectious process, inducing a heightened inflammatory response. Overall, our results indicate that cgpA codes for a protein that is key for the capacity of the bacteria to sense and respond to a plethora of extracellular cues.