Editors' ChoiceHost-Pathogen Interactions

Proline Promotes Virulence

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Science Signaling  26 Jan 2010:
Vol. 3, Issue 106, pp. ec31
DOI: 10.1126/scisignal.3106ec31

Certain bacteria and nematode worms exist in a symbiotic relationship. The bacteria live in the guts of the worms, where they are nonpathogenic, and are regurgitated when the worms parasitize an insect larvae host. Once released into the insect, the bacteria undergo a phenotypic change that assists the juvenile worms in infecting and digesting insect larvae (see Waterfield). Crawford et al. identified proline as a molecular trigger in insect extracts that stimulated the production of small molecules with virulence or antibiotic properties in two species of symbiotic bacteria, Photorhabdus luminescens TT01 and Xenorhabdus nematophila ATCC19061. Dose-response analysis showed that mM concentrations of L-proline were required to induce the production of the small molecules, and analysis of the hemolymph of four host insect larvae showed that this was a physiological concentration of L-proline. Osmotic stress also contributes to the regulation of virulence factors, contributing to the detection of a new host, and L-proline enhanced the bacterial response to high osmotic medium. Deletion of the candidate proline transporters from P. luminescens abolished the induction of some small molecules and increased the abundance of others, suggesting that L-proline or its metabolites differentially regulate the production of virulence factors. Proton motive force (PMF), a consequence of metabolic activity, also contributes to the regulation of bacterial virulence, and the addition of proline to the medium allowed P. luminescens to form colonies in the presence of drugs that disrupted PMF, suggesting that proline oxidation may provide an electron source for generation of PMF. Indeed, proline triggered redox reactions in bacteria in a chemical color assay. Thus, these bacteria appear to know they are in an insect by sensing proline, which then regulates metabolic pathways involved in producing antibiotic and virulence factors.

J. M. Crawford, R. Kontnik, J. Clardy, Regulating alternative lifestyles in entomopathogenic bacteria. Curr. Biol. 20, 69–74 (2010). [Online Journal]

N. Waterfield, Host-pathogen interactions: Proline gives insect pathogens the green light. Curr. Biol. 20, R13–R15 (2010). [Online Journal]

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